NZ250017A

NZ250017A - Quinolyl and isoquinoline-containing dipeptides and medicaments for antiretroviral use

Info

Publication number: NZ250017A
Application number: NZ250017A
Authority: NZ
Inventors: Guido Bold; Alexander Fassler; Marc Lang
Original assignee: Ciba Geigy Ag
Priority date: 1992-10-23
Filing date: 1993-10-21
Publication date: 1996-04-26
Also published as: MX9306588A; ZA937859B; IL107356A; SK115193A3; TW372972B; AU4907293A; ATE164592T1; EP0594540B1; CN1089606A; PL173529B1; NO933816D0; AU670121B2; CA2108934A1; HU214330B; EP0594540A1; KR940009177A; CZ223893A3; JPH06228132A; IL107356A0; FI934634A

Abstract

The invention relates to compounds of the formula I <IMAGE> in which R1 is acyl, and salts thereof, which have antiretroviral activity, in particular against AIDS.

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £50017 Publication Date: APS.. 1996. P.O. Journal No; lit£>3» NO DRAWING Patents Form No. 5 J^-PATENT office" 2 7 OCT 1993 MEW ZEALAND PATENTS ACT 1953 COMPLETE SPECIFICATION ANTIRETRQVIRAL ACYL COMPODIIDS WE, CIBA GEIGY AG, a Swiss corporation of Klybeckstrasse 141, 4002 Basle, SWITZERLAND hereby declare the invention, for which We pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: - 1 - (followed by page la) Ifc- 4-19330/A Antiretroviral acvl compounds The invention relates to novel antiretro viral compounds, to processes for the preparation of those compounds, to pharmaceutical compositions comprising those compounds, to those compounds for use in a therapeutic method of treating the human or animal body and to the use of those compounds for the therapeutic treatment of the human or animal body or for the preparation of pharmaceutical compositions. According to modern science, a whole range of diseases are caused by retroviruses. As far as is known at present, AIDS is a disease of the immune system caused by the retrovirus HIV ("Human Immunodeficiency Virus"). According to estimates by the WHO, the disease affects about 10 million people, is continuing to spread and in virtually all cases results in the death of the patient Hitherto the retroviruses HTV-1 andHTV-2 (HIV representing "Human Immunodeficiency Virus") have been identified as a cause of the disease and they have been characterised by molecular biology. From the point of view of treatment, in addition to previous limited ways of mitigating the symptoms of AIDS and certain preventive measures, there is particular interest in the search for compositions that interfere with the reproduction of the virus itself but do not damage the intact cells and tissues of the patient Retroviral protease is a proteolytic enzyme that, owing to an aspartate residue in the active centre, is regarded as an aspartate protease and participates in the maturation of new infectious virions in infected cells in the reproductive cycle of a number of retroviruses. For example, HTV-1 and HTV-2 each have in their genome a region that codes for a "gag-protease". That "gag-protease" is responsible for the correct proteolytic cleavage of the precursor proteins that are produced from the genome regions coding for the "Group Specific Antigens" (gag). During the cleavage, the structural proteins of the virus core are liberated. The "gag-protease" itself is a component of a precursor protein encoded by the pol-genome region of HTV-1 and HIV-2, which protein also contains the regions for the (fotlowed by page 2£ "reverse transcriptase" and the "integrase" and is thought to be cleaved by autopioteolysis. The "gag-protease" cleaves the major core protein p24 of HTV-1 and HTV-2 preferentially N-terminally of proline residues, for example in the divalent residues Phe-Pro, Leu-Pro or Tyr-Pro. It is a protease having a catalytically active aspartate residue in the active centre, a so-called aspartate protease. Because of the central role of the "gag-protease" in the processing of the mentioned "core-proteins", it is assumed that effective inhibition of that enzyme in vivo will suppress the assembly of mature virions, so that corresponding inhibitors can be used therapeutically. In general, attempts have been made for some time to provide compounds for controlling retroviral diseases, such as AIDS, that are effective in vivo as inhibitors of tb said retroviral gag-proteases, especially the gag-protease of HIV-1 (HTV-1 -protease), and also of those of HTV-2 and other AIDS viruses. The principal aim at present is to make available such compounds having the best possible pharmacokinetic properties. A requirement for therapeutic effectiveness in vivo is the achievement of good bioavailability, for example good absorptive capacity and/or a high blood level, also in the case of enteral, such as oral, administration, in order thus to obtain sufficiently high concentrations in the infected cells and/or good distribution in the organism. The object of the present invention is to provide structurally novel antiretro viral compounds having improved pharmacodynamic properties, which compounds preferably exhibit better absorption than do the corresponding unmodified antiretroviral compounds themselves in the case of enteral, especially oral, administration, and/or which result in blood levels, especially of the unmodified antiretroviral compound, that are higher than those obtainable with corresponding administration of the unmodified antiretroviral compounds themselves. The compounds of the invention are those of formula I S H () H i *="" v-' \j {J I 3- (D wherein Rj is acyl, and salts thereof. European Patent Application EP 0 432 695 (published 19 June 1991) refers to the compound of formula II (D) which is also included generically in EP 0 346 847 (published 19 June 1991) and for which a method of synthesis is described in EP 0 432 694 (published 11 December 1989). That compound is also referred to and studies are made of, for example, its action in vitro, on cell cultures and in vivo as well as its structure/action relationships in the following publications: Tucker, T. J., et aL, J. Med. Chem. 35,2525-2533 (1992); Robots, N. A., et al., Biochem. Soc. Transact 20,513-516 (1992); KrSusslich, H.-G., J. Virology 66, 567-572 (1992); Martin, J. A., et al., Biochem. Biophys. Res. Commun. 176. 180 - 188 (1991); Krohn et al., J. Med. Chem. 34. 3340-3342 (1991); Holmes, H. C., et al., Antiviral Chem. & Chemother. 2,287-293 (1991); Craig, J. G, et aL, Antiviral Chem. & Chemother. 2,181-186 (1991); Craig, J. C, et aL, Antiviral Res. 16,295-305 (1991); Roberts, N. A., et aL, Science 248.358-361 (1990); Overton, H. A., et al., Virology 179. 508-511 (1990); Muirhead, G. J., et aL, Brit J. Clin. PharmacoL 34(2), 170P (1992); Williams, p. E. O., et aL, Brit J. din. Pharmacol. 34(2). 155P (1992); Shaw et aL, Brit J. Clin. PharmacoL 34(2). 166P (1992); Johnson, V. A., et aL, J. Infectious Dis. 166(5). 1143 (1992); Phylip, L. H., FEBS Lett. 314(3). 449 (1992); EP 0 432 695 (published 19.06.1991); EP 0 513 917 (published 19.11.1992); Thompson, W. J., J. Am. Chem. Soc. 115.801 (1993); and EP 0 346 847 (published 20.12.1989). There is no mention or suggestion in any of those publications of compounds that contain a different radical instead of the hydrogen at the free hydroxy group in compounds of formula n. Surprisingly, it has now been found that when administered to mammals, especially when administered orally, compounds of formula II are present in the blood in significantly higher concentrations when a compound of formula I having a hydroxy group modified by Rx is administered than when the corresponding free compound of formula n is administered. The general terms and names used in the description of the present invention preferably have the following meanings: The compounds of formula I according to the invention can be present in various isomeric forms if the radical Rt can be present in various isomeric forms. For example, any asymmetric carbon atoms that may be present in the substituents Rx may each independently of the others be in the (R)-, (S)- or (R,S)-configuration and/or there may be cis/trans isomerism at multiple bonds, such as double bonds. Accordingly, the compounds of formula I may be in the form of isomeric mixtures, especially in the form of diastereo-isomeric mixtures or racemates, or in the form of pure isomers, especially pure enantiomers. The term "lower" used in the definition of groups or radicals, for example lower alkyl, lower alkoxycarbonyl etc., means that, unless expressly otherwise defined, the groups or radicals so defined contain up to and including 7, and preferably up to and including 4, carbon atoms. In the case of lower alkenyl and lower alkynyl, "lower" denotes the presence of from at least 2 to a maximum of 7, preferably from 2 to 4, carbon atoms, and in the case of lower alkenoyl or lower alkynoyl from 3 to 7, preferably 3 or 4, carbon atoms. Acyl R-x has, for example, up to 25, preferably up to 19, carbon atoms and is especially the acyl group of a carboxylic acid bonded via its carbonyl or the acyl group of an unsubstituted or substituted amino acid, also aminocarbonyl or the radical of an N-substituted carbamic acid bonded via its aminocarbonyl group or the radical of a semi-ester of carbonic acid bonded via carbonyl. Preferred acyl groups of a carboxylic acid are, for example, unsubstituted alkanoyl, alkenoyl or alkynoyl, or substituted alkanoyl, alkenoyl or alkynoyl, especially octanoyl, decanoyl, dodecanoyl or palmitoyl, unsubstituted or substituted lower alkanoyl, lower alkenoyl or lower alkynoyl, wherein the substituents are selected, for example, from one or more radicals, preferably from up to three radicals, especially from one radical or two radicals selected from the group consisting of hydroxy, lower alkoxy, lower alkoxy-lower alkoxy, lower alkoxy-lower alkoxy-lower alkoxy, phenoxy, naphthyloxy, phenyl-lower alkoxy, 2-halo-lower alkanoyl, such as 2-chloroacetyl, amino-, lower alkylamino- or di-lower alkylamino-lower alkoxy-2-lower alkanoyl, such as dimethylamino-lower alkoxyacetyl, amino-, lower alkylamino- or di-lower alkylamino-lower alkoxy-lower alkoxy-2-lower alkanoyl, such as dimethylamino-(2-lower alkoxyethyl)acetyl, lower alkanoyloxy, phenyl-lower alkanoyloxy, such as benzoyloxy or phenylacetoxy, halogen, such as fluorine, chlorine, bromine or iodine, especially fluorine or chlorine, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, such as benzyloxycarbonyl, carbamoyl, lower alkyl-carbamoyl, hydroxy-lower alkylcarbamoyl, di-lower alkylcarbamoyl, bis(hydroxy-lower alkyl)carbamoyl, carbamoyl the nitrogen atom of which is a constituent of a 5- to 7-membered heterocyclic ring that may contain a further hetero atom selected from oxygen, sulfur, nitrogen and lower alkyl-substituted, such as methyl- or ethyl-substituted, nitrogen, for example pyrrolidinocarbonyl, morpholinocarbonyl, thiomorpholino-carbonyl, piperidin-1 -y lcarbony 1, piperazin- 1-ylcarbonyl or 4-lower alky lpiperazin-1 -yl-carbonyl, such as 4-methylpiperazin- 1-ylcarbonyl; cyano, oxo, cycloalkyl, for example Cs-Cscycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, bicyclo-alkyl, for example Cg-C^bicycloalkyl, such as decahydronaphth-2-yl, endo- or exo-2-norbornyl, bicyclo[2.2.2]oct-2-yl or bicyclo[3.3.1]non-9-yl, tricycloalkyl, for example C9-C14tricycloalkyl, such as 1- or 2-adamantyl, cycloalkenyl, for example C^Cgcyclo- alkenyl, such as 1-cyclohexenyl or 1,4-cyclohexadienyl, bicycloalkenyl, for example 5-norbomen-2-yl or bicyclo[2.2.2]octen-2-yl, heterocyclyl, which is a saturated, partially saturated or unsaturated ring containing from 3 to 7, preferably from 5 to 7, ring atoms and up to four heteroatoms independently selected from nitrogen, sulfur and oxygen, preferably 1 or 2 of the mentioned heteroatoms, the ring being present as such or in once or twice, preferably once, benzo-, cyclopenta-, cyclohexa- or cyclohepta-fused form, heterocyclyl being unsubstituted or substituted especially by lower alkyl, lower alkanoyl, hydroxy, lower alkoxy, phenyl-lower alkoxy, such as benzyloxy, hydroxy-lower alkyl, such as hysroxymethyl, halogen, cyano and/or by trifluoromethyl, for example pyrrolyl, 2,5-dihydropynolyl, furanyl, thienyl, tetrahydrofiiranyl, cyclohepta[b]pynolyl, pyrrolidinyl, imidazolyl, imidazolidinyl, pyrazolinyL, pyrazolidinyl, triazolyl, such as 1,2,3-, 1,2,4- or 1,3,4-triazolyl, tetrazolyl, such as 1- or 2-tetrazolyl, tetrahydro-oxazolyl, tetrahydio-isoxazolyl, tetrahydro-thiazolyl, tetrahydro-isothiazolyl, indolyl, isoindolyl, quinolyl, isoquinolyl, benzimidazolyl, benzofuranyl, pyridyl, pyrimidinyl, piperidinyl, piperazin-l-yl, morpholino, thiomorpholino, S ,S -dioxothiomorpholino, 1,2-dihydro- or 1,2,3,4-tetrahydroquinolyl, or 1,2-dihydro- or 1,2,3,4-tetrahydio-isoquinolyl, the mentioned radicals being unsubstituted or substituted as above, especially by lower alkyl, for example as in 4-lower alkyl-piperazin- 1-yl, such as 4-methyl- or 4-ethyl-piperazin-l-yl, by lower alkanoyl, for example as in 4-lower alkanoyl-piperazin-l-yl, such as 4-acetyl-piperazin-l-yl, or by hydroxy-lower alkyl, for example as in 5-hydroxy-methylfuran-2-ylcarbonyl; and aryl, preferably Cg-C12aryl, for example phenyl, naphthyl, such as 1- or 2-naphthyl, indanyl, such as 1- or 2-indanyl, indenyl, such as indcn-l-yl, or fluorenyl, such as fluoren-9-yl, aryl being unsubstituted or mono- or poly-substituted, preferably mono-substituted, for example, by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower al^yl, such as trifluoromethyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above, especially heterocyclylmethyl wherein heterocyclyl is bonded via a ring nitrogen atom, for example piperidinomethyl, piperazin-1 -ylmethyl, 4-lower alkyl-piperazin- 1-yl-methyl, such as 4-methyl- or 4-ethyl-piperazin-l-ylmethyl, 4-lower alkanoyl-piperazin-1-ylmethyl, such as 4-acetyl-piperazin-1 -ylmethyl, morpholinomethyl or thiomorpho-linomethyl, cyano and/or by nitro, and especially phenyl substituted in the p-position by one of the mentioned radicals; for example lower alkanoyl, such as formyl, acetyl, propionyl, butyryl, methylpropionyl, pivaloyl, n-pentanoyl, hexanoyl or heptanoyl, such as n-heptanoyl, hydroxy-lower alkanoyl, for example S-hydroxypropionyl, lower alkoxy-lower alkanoyl, for example lower alkoxyacetyl or lower alkoxypropionyl, such as methoxyacetyl, 3-methoxypropionyl or n-butoxyacetyl, lower alkoxy-lower alkoxy-lower alkanoyl, such as 2-(2-methoxy-ethoxy) acetyl, lower alkoxy-lower alkoxy-lower alkoxy-lower alkanoyl, such as 2-(2-(2-methoxyethoxy)ethoxy)acetyl, phenoxy-lower alkanoyl, for example phenoxy-acetyl, naphthyloxy-lower alkanoyl, for example a- or p-naphthyloxyacetyl, phenyl-lower alkoxy-lower alkanoyl, such as benzyloxyacetyl, 2-halo-lower alkanoyl, such as 2-chloro-acetyl, amino-, lower alkylamino- or di-lower alkylamino-lower alkoxy-2-lower alkanoyl, such as dimethylamino-lower alkoxyacetyl, amino-, lower alkylamino- or di-lower alkylamino-lower alkoxy-lower alkoxy-2-lower alkanoyl, such as dimethylaxnino-(2-lower alkoxyethoxy)acetyl, lower alkanoyloxy-lower alkanoyl, for example lower alkanoyloxy-acetyl or lower alkanoyloxypropionyl, such as acetoxyacetyl or P-acetoxypropionyl, halo-lower alkanoyl, for example a-haloacetyl, such as a-chloro-, a-bromo-, a-iodo-, a,a,a-tri-fluoro- or a,a,a-trichloro-acetyl, or halopropionyl, such as p-chloro- or p-bromo-propionyl, carboxy-lower alkanoyl, for example carboxyacetyl or 3-carboxypropionyl, lower alkoxycarbonyl-lower alkanoyl, for example lower alkoxycarbonylacetyl or lower alkoxycaibonylpropionyl, such as methoxycarbonylacetyl, p-methoxycarbonylpropionyl, ethoxycaibonylacetyl, p-ethoxycarbonylpropionyl, tert-butoxycarbonylacetyl or fi-tert-butoxycarbonylpropionyl, carbamoyl-lower alkanoyl, for example carbamoylacetyl or p-carbamoylpropionyl, lower alkylcarbamoyl-lower alkanoyl, for example methyl-caibamoylacetyl or 0-(N-lower alkyl)carbamoylpropionyl, such as (J-CN-inethyl)-, P-(N-ethyl)-, p-(N-(n-propyl))-carbamoyl- or p-(N-(n-hexyl))-caibamoyl-propionyl, di-lower alkylcarbamoyl-lower alkanoyl, for example dimethylcarbamoylacetyl, p-(N,N-(di-lower alkyl)carbamoyl)propionyl, such as p-(N,N-dimethyl)-, P-(N,N-di-ethyl)-, P-(N,N-di-(n-propyl)-carbamoyl)- or P-(N,N-di-(n-hexyl))-carbamoyl-propionyl, P-pyirolidinocarbonylpropionyl, P-morpholinocarbonylpropionyl, P-thiomorpholino-carbonylpropionyl, P-piperidin- 1-ylcarbonylpropionyl, p-piperazin- 1-ylcaibonylpropionyl or p-(4-lower alkyl-piperazin-l-ylcarbonyl)-propionyl, such as p-(4-methylpiperazin-l-yl-carbonyl)propionyl, oxo-lower alkanoyl, for example acetoacetyl or propionylacetyl, hydroxy-carboxy-lower alkanoyl, for example a-hydroxy-a-carboxy-acetyl or a-hydroxy-P-carboxypnopionyl, hydroxy-lower alkoxycarbonyl-lower alkanoyl, for example a-hydroxy-a-ethoxy- or -methoxy-cazbonylacetyl or a-hydroxy-p-ethoxy- or -methoxy-carbonyl-propionyl, a-acetoxy-a-methoxycarbonyl-acetyl, dihydroxy-carboxy-lower alkanoyl, for example a.p-dihydroxy-p-carboxy-propionyl, dihydroxy-lower alkoxycarbonyl-lower alkanoyl, for example a,p-dihydroxy-p-ethoxy- or -methoxy- carbonyl-piopionyl, a,p-diacetoxy-p-methoxycarbonyl-propionyl, a-naphthyloxy-carboxy-lower alkanoyl, for example 2-a-naphthyloxy-4-carboxy-butyryl, a-naphthyl-oxy-lower alkoxycarbonyl-lower alkanoyl, for example a-naphthyloxy-ethoxycarbony.1-acetyl, 2-a-naphthyloxy-ethoxycarbonyl-propionyl or 2-a-naphthyloxy-4-tert-butoxy-carbonylbutyryl, a-naphthyloxy-benzyloxycarbonyl-lower alkanoyl, for example 2-a-naphthyloxy-3-benzyloxycarbonyl-propionyl, a-naphthyloxy-carbamoyl-lower alkanoyl, for example 2-a-naphthyloxy-4-carbamoyl-butyryl, a-naphthyloxy-cyano-lower alkanoyl, for example a-naphthyloxy-cyano-acetyl or 2-a-naphthyloxy-4-cyanobutyryl, a-naphthyloxy-oxo-lower alkanoyl, for example 2-a-naphthyloxy-4-oxo-pentanoyl, hetcrocyclyl-lower alkanoyl, for example unsubstituted or substituted pyrrolylcarbonyl, for example 2- or 3-pyrrolylcarbonyl, furylcarbonyl, for example 2-furylcarbonyl, 5-hydroxymethyl-furan-2-ylcarbonyl, thienylcarbonyl, for example 2-thienylcarbonyl, pyridyl-lower alkanoyl, such as pyridylcarbonyl, for example 2-, 3- or 4-pyridylcaxbonyl, pyridylacetyl, for example 2-pyridylacetyl, or pyridylpropionyl, for example 3-(2-pyridyl)-propionyl, quinolylcarbonyl, such as quinolin-2-ylcarbonyl, isoquinolinylcarbonyl, such as isoquinolin-3-ylcarbonyl, unsubstituted or substituted indolylcarbonyl, for example 2-, 3-or S-indolylcaibonyl, 1-methyl-, 5-methyl-, 5-methoxy-, 5-benzyloxy-, 5-chloro- or 4,5-dimethyl-indolyl-2-carbonyl, cyclohepta[b]pyrrolyl-5-carbonyl, pyrrolidin-(2- or 3-)yl-carbonyl (pyrrolidinyl-2-carbonyl (= prolyl) preferably being in the D- or L-fonn), hydroxypyrrolidinylcarbonyl, for example 3- or4-hydroxypyrrolidinyl-2-caibonyl, oxo-pyrrolidinylcarbonyl, for example 5-oxopyrrolidinyl-2-carbonyl, piperidinylcarbonyl, for example 2-, 3- or4-piperidinylcarbonyl, 1,23,4-tetrahydroquinolylcaibonyl, for example l,2,3,4-tetrahydroquinolyl-2-, -3- or -4-carbonyl, or 1,2,3,4-tetrahydroisoquinolylcarbonyl, for example 1,2,3,4-tetrahydroisoquinolyl-1 -, -3- or -4-caibonyl, imidazolyl-lower alkanoyl, such as imidazolylcarbonyl, for example imidazol-1 -ylcaibonyl or imidazol- 4-ylcarbonyl, imidazolylacetyl, for example 4-imidazolylacetyl, or imidazolylpropionyl, for example 3-(4-imidazolyl)propionyl, moipholinocarbonyl, thiomorpholinocarbonyl, morpholinoacetyl, thiomorpholinoacetyl, 4-lower alkyl- 1-piperazinoacetyl, such as 4-methyl-piperazinoacetyl, indolylacetyl or benzofuranylacetyl, lower alkenoyl, for example acryloyl, vinylacetyl, crotonoyl or 3- or 4-pentenoyl, lower alkynoyl, for example propioloyl or 2- or 3-butynoyl, cycloalkylcarbonyl, for example cyclopropyl-, cyclobutyl-, cyclopentyl- or cyclohexyl-carbonyl, bicycloalkylcarbonyl, for example decahydro-naphthyl-2-carbonyl, endo- or exo-norbomyl-2-carbonyl, bicyclo[2.2.2]oct-2-ylcarbonyl or bicyclo[3.3.1]non-9-ylcarbonyl, tricycloalkylcarbonyl, for example 1- or 2-adamantyl-carbonyl, cycloalkenylcarbonyl, for example 1-cyclohexenylcarbonyl or 1,4-cyclohexa-dienylcarbonyl, bicycloalkenylcarbonyl, for example 5-norbornen-2-ylcarbonyl or bicyclo[2.2.2]octen-2-ylcarbonyl, cyclopropylacetyl, cyclopentylacetyl, cyclohexylacetyl or 3-cyclohexylpropionyl, cycloalkyl-lower alkenoyl, for example cyclohexylaciyloyl, cycloalkenyl-lower alkanoyl, for example 1-cyclohexenylacetyl or 1,4-cyclohexadienyl-acetyl, phenyl-lower alkanoyl, for example benzoyl, phenylacetyl or 3-phenylpiopionyl, that is unsubstituted or mono- or poly-substituted in the phenyl radical by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, for example methoxy, piperidinomethyl, piperazin-1-ylmethyl, 4-lower alkyl-piperazin-1 -ylmethyl, such as 4-methyl- or 4-ethyl-piperazin-1-ylmethyl, 4-lower alkanoyl-piperazin-1 -ylmethyl, such as 4-acetyl-piperazin- 1-ylmethyl, morpholi nomethyl, thiomorpholinomethyl, cyano and/or by nitro, or a-naphthyl- or P-naphthyl-lower alkanoyl wherein naphthyl is unsubstituted or mono- or poly-subsdtuted by lower alkyl, for S imple methyl, phenyl, halogen, for example chlorine, hydroxy, lower alkoxy, for example methoxy, and/or by nitro, and lower alkanoyl in phenyl-, a-naphthyl- or P-naphthyl-lower alkanoyl may be unsubstituted or substituted, for example, by hydroxy, lower alkoxy, lower alkanoyloxy, caiboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, such as benzyloxycarbonyl, carbamoyl, lower alkylcarbamoyl, di-lower alkylcarbamoyl, cyano and/or by oxo and may be branched, for example 4-chloromethyl-, 4-bromomethyl-, 4-fluoro-, 4-chloro-, 4-methoxy-, 4-morpholinomethyl-, 4-thiomorpholinomethyl-, 4-cyano- or 4-nitro-benzoyl, a-naphthylacetyl, p-naphthylacetyl, lower alkylphenylacetyl, such as 4-methyl-phenylacetyl, lower alkoxyphenylacetyl, such as 4-methoxyphenylacetyl, 2-lower alkoxy-2-phenylacetyl, such as (R)- or (S)-2-methoxy-2-phenylacetyl, 3-(p-hydroxy-phenyl)-propionyl, diphenylacetyl, di(4-methoxyphenyl)acetyl, triphenylacetyl, 3-a- or 3-p-naphthylpropionyl, 3-phenyl- or 3-a-naphthyl-2-hydroxy-propionyl, 3-phenyl- or 3-a-naphthyl-2-lower alkoxy-propionyl, such as 3-phenyl- or 3-a-naphthyl-2-neo-pentyloxy-propionyl, 3-phenyl-2-pivaloyloxy- or -2-acetoxy-propionyl, 3-a-naphthyl-2-pi-valoyloxy- or -2-acetoxy-propionyl, 3-phenyl- or 3-a-naphthyl-2-carboxymethylpropionyl, 3-phenyl- or 3-a-naphthyl-2-lower alkoxycarbonyl-propionyl, such as 3-a-naphthyl- 2-ethoxycarbonyl-propionyl, 3-phenyl- or 3-a-naphthyl-2-benzyloxycarbonylmethyl-propionyl, 3-phenyl- or 3-a-naphthyl-2-caibamoyl-propionyl, 3-phenyl- or 3-a-naphthyl-2-tert-butylcarbamoyl-piopionyl, 3-phenyl- or 3-a-naphthyl-2-cyano-propionyl, 3-phenyl-or 3-a-naphthyl-2-cyanomethyl-propionyl, 3-phenyl- or 3-a-naphthyl-2-acetonyl-pro-pionyl, 2-benzyl- or 2-a-naphthylmethyl-4-cyano-butyiyl, 4-phenyl- or 4-a-naphthyl-3-carboxy-butyryl, 4-phenyl- or 4-a-naphthyl-3-benzyloxycarbonyl-butyiyl, 2-benzyl- or 2-a-naphthylmethyl-4-oxo-pentanoyl, phenyl-lower alkenoyl, for example P-phenyl-acryloyl or P-phenylvinylacetyl, naphthylcarbonyl, for example a- or P-naphthylcarbonyl, <£5 0 0 1 7 -10- indenylcarbonyl, for example 1-, 2- or 3-indenylcarbonyl, or indanylcarbonyl, for example 1- or 2-indanylcarbonyl. Preferred acyl groups Ri of a semiester of carbonic acid are, for example, unsubstituted or substituted alkoxycarbonyl, especially lower alkoxycarbonyl, for example methoxy-, ethoxy- or tert-lower alkoxy-carbonyl, such as tert-butoxycarbonyl, 2-halo-lower alkoxycarbonyl, for example 2-chloro-, 2-bromo-, 2-iodo- or 2,2,2-trichloro-ethoxycarbonyl; aryl-lower alkoxycarbonyl, for example arylmethoxycarbonyl, wherein aryl preferably has from 6 to 14 carbon atoms, is unsubstituted or mono- or poly-substituted, preferably mono-substituted, for example, by lower alkyi, for example methyi, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, such as trifluoromethyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above as a substituent of lower alkanoyl, especially heterocyclylmethyl wherein heterocyclyl is bonded via a ring nitrogen atom, for example piperidinomethyl, piperazin-1-ylmethyl, 4-lower alkyl-piperazin-1-ylmethyl, such as 4-methyl- or 4-ethyl-piperazin-1 -ylmethyl, 4-lower alkanoyl-pipeiazin-l-ylmethyl, such as 4-acetyl-piperazin-1 -ylmethyl, morpholinomethyl or thiomorpholinomethyl, cyano and/or by nitro, and is especially phenyl, 1- or 2-naphthyl, fluorenyl or phenyl mono- or poly-substituted by lower alkyl, for example methyl or tert-butyl, lower alkoxy, for example methoxy, ethoxy or tert-butoxy, hydroxy, halogen, for example fluorine, chlorine or bromine, and/or by nitro, for example phenyl-lower alkoxycarbonyl, such as benzyloxy-carbonyl, 4-methoxybenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, diphenyl-lower alkoxycarbonyl, such as diphenylmethoxycarbonyl, di(4-methoxyphenyl)methoxy-carbonyl, trityloxycaibonyl or fluorenyl-lower alkoxycarbonyl, such as 9-fluorenyl-methoxycarbonyl; or also heterocyclyl-lower alkoxycarbonyl wherein heterocyclyl is as defined above as a substituent of alkanoyl, for example furan-2-ylmethoxycarbonyl or pyridin-2-, -3- or -4-ylmethoxycarbonyl. The definitions falling under the definition of acyl groups Rj of a semiester of carbonic acid may preferably be omitted from all the definitions of compounds of formula 1 mentioned hereinbefore and hereinafter. A preferred acyl group Ri of an N-substituted carbamic acid is an aminocarbonyl radical wherein the amino group carries one or two substituents selected independently of one another from *50017 -11- unsubstituted or substituted lower alkyl, the substituents of which are selected from those mentioned above for substituted lower alkanoyl and are present in the number defined therein, preferably substituents selected from hydroxy, lower alkoxy, phenoxy, naphthyloxy, lower alkanoyloxy, phenyl-lower alkanoyloxy, such as benzoyloxy or phenylacetoxy, halogen, such as fluorine, chlorine, bromine or iodine, especially fluorine or chlorine, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, such as benzyloxycarbonyl, carbamoyl, lower alkylcarbamoyl, hydroxy-lower alkylcarbamoyl, di-lower alkylcarbamoyl, bis(hydroxy-lower alkylcarbamoyl, cyano, oxo and Cg-C^aryl, for example phenyl, naphthyl, such as 1- or 2-naphthyl, indanyl, such as 1- or 2-indanyl, indenyl, such as inden-l-yl, or fluorenyl, such as fluoren-9-yl, aryl being unsubstituted or mono- or poly-substituted, preferably mono-substituted, for example, by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, such as trifluoromethyl, cyano and/or by nitro, especially phenyl substituted in the p-position by one of the mentioned radicals; especially unsubstituted lower alkyl, such as methyl or ethyl; and aryl which preferably has from 6 to 14 carbon atoms and is unsubstituted or mono- or poly-substituted, preferably mono-substituted, for example, by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkyl- . carbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, such as trifluoromethyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above as a substituent of lower alkanoyl, especially heterocyclylmethyl wherein heterocyclyl is bonded via a ring nitrogen atom, for example piperidinomethyl, piperazin-l-ylmethyl, 4-lower alkyl-piperazin-1-ylmethyl, such as 4-methyl- or 4-eihyl-piperazin-l-ylmethyl, 4-lower alkanoyl-piperazin- 1-ylmethyl, such as 4-acetyl-piperazin- 1-ylmet hyl, morpho-linomethyl or thiomorpholinomethyl, cyano and/or by nitro, preferably correspondingly substituted phenyl or 1- or 2-naphthyl, the radical of an N-substituted carbamic acid carrying not more than one of the mentioned aryl radicals at the nitrogen atom; an acyl group Rx of an N-substituted carbamic acid is especially mono- or di-lower alkylamino-carbonyl, such as N-methyl-, N-ethyl-, N,N-dimethyl- or N,N-diethyl-aminocarbonyl, or phenyl-lower alkylaminocarbonyl wherein phenyl is unsubstituted or substituted by the ^ j u y -12- radicals mentioned in the definition of aryl, for example by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl or trifluoromethyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, carboxy and/or by cyano, preferably by up to three of those substituents selected independently of one another, especially by one of those substituents, for example in the p-position, such as in N-benzyl-, N-(4-fluorobenzyl)-, N-(4-chlorobenzyl)-, N-(4-trifluoromethylbenzyl)- or N-(4-cyanobenzyl)-aminocarbonyl; especially preferred is aminocarbonyl substituted by only one radical at the nitrogen atom, for example N-lower alkylaminocarbonyl, such as N-methyl- or N-ethyl-aminocarbonyl, or phenyl-lower alkylaminocarbonyl wherein phenyl is unsubstituted or substituted by the radicals mentioned in the definition of aryl, for example by lower alkyl, such as methyl, halo-lower alkyl, such as chloro- or bromo-methyl or trifluoromethyl, halogen, such as fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, carboxy and/or by cyano, preferably by up to three of those substituents selected independently of one another, especially by one of those substituents, for example in the p-position, such as in N-benzyl-, N-(4-fluorobenzyl)-, N-(4-chlorobenzyl)-, N-(4-tri-fluoromethylbenzyl)- or N-(4~cyanobenzyl)-aminocarbonyl. The definitions falling under the definition of acyl groups Rx of an N-substituted carbamic acid, and the radical aminocarbonyl Rj may preferably be omitted from all the definitions of compounds of formula I mentioned hereinbefore and hereinafter. Preferred acyl groups Rj of an unsubstituted or substituted amino acid are formed by the amino acid residues of an a-, p-, y- or 5-amino acid that is bonded via its carbonyl group, especially of a natural a-amino acid having the L-configuration, such as those normally occurring in proteins, or an epimer of such an amino acid, that is to say having the unnatural D-configuration, or a DJL-isomeric mixture thereof, a homologue of such an amino acid, for example wherein the amino acid side chain has been lengthened or shortened by one or two methylene groups, wherein the amino group is in the p-, y- or 8-position and/or wherein a methyl group has been replaced by hydrogen, a substituted aromatic amino acid wherein the aromatic radical has from 6 to 14 carbon atoms, for example a substituted phenylalanine or phenylglycine wherein the phenyl may be mono- or poly-substituted by lower alkyl, for example methyl, hydroxy, lower alkoxy, for example methoxy, lower alkanoyloxy, for example acetoxy, amino, lower alkylamino, for example methylamino, di-lower alkylamino, for example dimethylamino, lower alkanoylamino, for example acetylamino or pivaloylamino, lower alkoxycarbonyiamino, for example tert-butoxy-carbonylamino, arylmethoxycarbonylamino wherein aryl preferably has from 6 to 14 - 13- carbon atoms, for example benzyloxycarbonylamino or 9-fluorenylmethoxycarbonyl-amino, halogen, for example fluorine, chlorine, bromine or iodine, carboxy and/or by nitro, a benzo-fused phenylalanine or phenylglycine, such as a-naphthylalanine, or a hydrogenated phenylalanine or phenylglycine, such as cyclohexylalanine or cyclohexyl-glycine. Within the context of the mentioned definitions, acyl groups of amino acids that have already been mentioned, such as prolyl, indoline-2-carbonyl, 1,2,3,4-tetrahydroiso-quinoline-3-carbonyl and trans-3- and trans-4-hydroxyprolyl which have already appeared in the definition of substituted lower alkanoyl Rj, are excepted, but only with the sole aim of avoiding overlapping of the definitions. Those amino acid radicals may be substituted at free amino or hydroxy functions, preferably at a free amino function, by one of the radicals mentioned above under acyl Rx as the acyl group of a carboxylic acid or a semiester of carbonic acid, by unsubstituted or substituted alkyl, especially lower alkyl, such as methyl, ethyl, isopropyl, n-propyl or n-butyl, wherein the substituents are selected, for example, from one or more radicals, preferably from up to three radicals, especially from one radical selected from the group consisting of hydroxy, lower alkoxy, phenoxy, naphthyloxy, lower alkanoyloxy, halogen, such as fluorine, chlorine, bromine or iodine, especially fluorine or chlorine, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, such as benzyloxycarbonyl, carbamoyl, lower alkylcarbamoyl, hydroxy-lower alkylcarbamoyl, di-lower alkylcarbamoyl, bis (hydroxylower alkyl)carbamoyl, cyano, oxo, cycloalkyl, for example C3-C8cyclo-alkyl, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, bicycloalkyl, for example Cg-C^bicycloalkyl, such as decahydronaphth-2-yl, endo- or exo-2-noibornyl, bicyclo[2.2.2]oct-2-yl or bicyclo[3.3.1]non-9-yl, tricycloalkyl, for example C9-C14tricycloalkyl, such as 1- or 2-adamantyl, cycloalkenyl, for example C^-Cgcyclo-alkenyl, such as 1-cyclohexenyl or 1,4-cyclohexadienyl, bicycloalkenyl, for example 5-norbomen-2-yl or bicyclo[2.2.2]octen-2-yl, heterocyclyl, which is a saturated, partially saturated or unsaturated ring containing from 3 to 7, preferably from 5 to 7, ring atoms and up to four heteroatoms independently selected from nitrogen, sulfur and oxygen, preferably 1 or 2 of the mentioned heteroatoms, the ring being present as such or in once or twice, preferably once, benzo-, cyclopenta-, cyclohexa- or cyclohepta-fused form, heterocyclyl being unsubstituted or substituted especially by lower alkyl, lower alkanoyl, hydroxy, lower alkoxy, phenyl-lower alkoxy, such as benzyloxy, hydroxy-lower alkyl, such as hysroxymethyl, halogen, cyano and/or by trifluoromethyl, for example pyrrolyl, 2,5-dihydropynolyl, furanyl, thienyl, tetrahydrofuranyl, cyclohepta[b]pyrrolyl, J u Q 1 - 14- pynolidinyl, imidazolyl, imidazolidinyl, pyrazolinyl, pyrazolidinyl, triazolyl, such as 1,2,3-. 1,2,4- or 1,3,4-txiazolyl, tetrazolyl, such as 1- or 2-tetrazolyl, tetrahydro-oxazolyl, tetrahydro-isoxazolyl, tetrahydro-thiazolyl, tetrahydro-isothiazolyl, indolyl, isoindolyl, quinolyl, isoquinolyl, benzimidazolyl, benzofuranyl, pyridyl, pyrimidinyl, piperidinyl, piperazin-l-yl, morpholino, thiomorpholino, S ,S-dioxothiomorpholino, 1,2-dihydro- or 1,2,3,4-tetrahydro-quinolyl, or 1,2-dihydro- or 1,2,3,4-tetrahydro-isoquinolyl, the mentioned radicals being unsubstituted or substituted as mentioned above, especially by lower alkyl, for example as in 4-lower alkyl-piperazin- 1-yl, such as 4-methyl- or 4-ethyl-piperazin- 1-yl, or by lower alkanoyl, for example as in 4-lower alkanoyl-piperazin-l-yl, such as 4-acetyl-piperazin-1 -yl, and aryl, preferably Cg-C^aryl, for example phenyl, naphthyl, such as 1- or 2-naphthyl, indanyL, such as 1- or 2-indanyl, indenyl, such as inden-l-yl, or fluorenyl, such as fluoren-9-yl, the mentioned aryl radicals being unsubstituted or mono- or poly-substituted, preferably mono-substituted, for example, by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, such as trifluoromethyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above, especially heterocyclylmethyl wherein heterocyclyl is bonded via a ring nitrogen atom, for example piperidinomethyl, piperazin-1 -ylmethyl, 4-lower alkyl-piperazin-1 -ylmethyl, such as 4-methyl- or 4-ethyl-piperazin- 1-ylmethyl, 4-lower alkanoyl-pipcxazin- 1-ylmethyl, such as 4-acetyl-piperazin-1-ylmethyl, morpholinomethyl, thiomorpholinomethyl, cyano and/or by nitro, especially phenyl substituted in the p-position by one of the mentioned radicals; especially by a correspondingly substituted lower alkyl radical, especially correspondingly substituted methyl, preferably benzyl, diphenylmethyl, trityl, 2-, 3- or 4-pyridylmethyl, or may be substituted by one of the radicals mentioned as protecting groups in the section relating to processes, or may be derivatised at caiboxy groups. Especially preferred is the residue, bonded via its a-carbonyl group, of an amino acid selected from glycine (H-Gly-OH), alanine (H-Ala-OH), 2-aminobutyric acid, 3-amino-butyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, 5-aminopentanoic acid, 3-aminohexanoic acid, 4-aminohexanoic acid or S-aminohexanoic acid, valine (H-Val-OH), norvaline (a-aminovaleric acid), leucine (H-Leu-OH), isoleucine (H-He-OH), norleucine (a-aminohexanoic acid, H-Nle-OH), serine (H-Ser-OH), homoserine (a-aixiino-Y-hydroxybutyric acid), threonine (H-Thr-OH), methionine * 5 0 0 1 ] -15- (H-Met-OH), cysteine (H-Cys-OH), phenylalanine (H-Phe-OH), tyrosine (H-Tyr-OH), 4-aminophenylalanine, 4-chlorophenylalanine, 4-carboxyphenylalanine, ($-phenylserine (P-hydroxyphenylalanine), phenylglycine, a-naphthylalanine (H-Nal-OH), cyclohexyl-alanine (H-Cha-OH), cyclohexylglycine, tryptophan (H-Trp-OH), aspartic acid (H-Asp-OH), asparagine (H-Asn-OH), aminomalonic acid, aminomalonic acid monoamide, glutamic acid (H-Glu-OH), glutamine (H-Gln-OH), histidine (H-His-OH), arginine (H-Arg-OH), lysine (H-Lys-OH), 5-hydroxylysine, ornithine (a,5-diaminovaleric acid), 3-aminopropanoic acid, a,Y-diaminobutyric acid and a,|3-diaminopropionic acid, especially the residue of an aliphatic amino acid selected from alanine, valine, norvaline, leucine, 3-aminopropionic acid, 2-aminobutyric acid, 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, 5 - aminopentanoic acid, 3-aminohexanoic acid, 4-aminohexanoic acid or 5-aminohexanoic acid and isoleucine or an amino acid selected from glycine, asparagine, glutamine, methionine, lysine and phenylalanine, it being possible for each of the mentioned amino acids to be in the D-, L- or (DJL)-fonn, preferably in the L-form (except in cases where there is no asymmetric carbon atom, for example in the case of glycine), an a-amino group, if present, is unsubstituted or is mono- or di-N-alkylated, for example by lower alkyl, such as methyl, n-propyl or n-butyl, by amino-lower alkyl, such as 3-axninopropyl, by phenyl- or naphthyl-amino-lower alkyl, such as 3-phenylamino-propyl, by phenyl-lower alkyl, such as benzyl, by diphenylmethyl, by trityl and/or by heterocyclyl-lower alkyl wherein heterocyclyl is as defined above for an acyl group Rj of a carboxylic acid, especially by heterocyclylmethyl, for example furanyl-lower alkyl, such as 2-furylmethyl, thienyl-lower alkyl, such as 2-thienylmethyl, imidazolyl-lower alkyl, such as imidazol-4-ylmethyl, or 2-, 3- or 4-pyridyl-lower alkyl, such as 2-, 3- or 4-pyridylmethyl, and/or is N-aeylated, for example, by the acyl groups of a carboxylic acid mentioned above in the definition of Rlf especially by unsubstituted or substituted lower alkanoyl, as defined above, especially by acetyl, piopionyl, pivaloyl, heterocyclyl-lower alkanoyl, as defined above for acyl Rlt for example furan-2-ylcarbonyl, 5-hydroxy-methyl-furan-2-ylcarbonyl, 2-, 3- or 4-pyridylcarbonyl, morpholinocarbonyl, thiomorpho-linocarbonyl, indolylacetyl or benzofutanylacetyl, aryl-lower alkanoyl, such as benzoyl or phenylacetyl, or the acyl groups of a semiester of carbonic acid mentioned above in the definition of Rj, especially lower alkoxycarbonyl, such as tert-butoxycarbonyl, or aryl-lower alkoxycarbonyl, such as benzyloxycaibonyl, a carboxy group of the side chain is present in free form or in esterified or amidated form, for example in the form of a lower alkyl ester group, such as methoxycarbonyl or tert-butoxycarbonyl, an aryl ester group or an aryl-lower alkyl ester group, wherein aryl is £ 0 U U 1 -16- phenyl, 4-nitrophenyl, naphthyl, fluorenyl or biphenylyl, for example in the form of a 4-nitrophenoxycarbonyl, benzyloxycarbonyl or 9-fluorcnylmethoxycarbonyl group, or in the form of a carbamoyl, a lower alkylcarbamoyl, such as methylcarbamoyl, a di-lower alkylcarbamoyl, such as dimethylcarbamoyl, a mono- or di(hydroxy-lower alkylcarbamoyl, such as hydroxymethylcarbamoyl or di(hydroxymethyl)carbamoyl, or a mono-or di-(carboxy-lower alkyl)carbamoyl group, such as a carboxymethylcarbamoyl or di(carboxymethyl)carbamoyl group, an amino group of the side chain that is not in the a-position is present in free form or in alkylated form, for example in the form of mono- or di-lower alkylamino, such as n-butyl-amino or dimethylamino, or in acylated form, for example in the form of lower alkanoyl-amino, such as acetylamino or pivaloylamino, amino-lower alkanoylamino, such as 3-amino-3,3-dimethylpropionylamino, aryl-lower alkanoylamino wherein aryl has from 6 to 14 carbon atoms, for example phenyl, naphthyl or fluorenyl, and is unsubstituted or substituted by lower alkyl, hydroxy, lower alkoxy, carboxy, carbamoyl or by sulfamoyl, such as 4-hydroxyphenylbutyiyl, lower alkoxycarbonylamino, such as tert-butoxy-carbonylamino, arylmethoxycarbonylamino wherein aryl has from 6 to 14 carbon atoms, such as benzyloxycarbonylamino or 9-fluorenylmethoxycarbonylamino, piperidyl-1-carbonyl, morpholinoc arbonyl, thiomorpholinocarbonyl or S,S-dioxothiomoipholino-caibonyl, and/or a hydroxy group of the side chain is present in free form or in etherified or esterified form, for example in the form of a lower alkoxy, such as methoxy or tert-butoxy, aryl-lower alkoxy, especially phenyl-lower alkoxy, such as benzyloxy, lower alkanoyloxy, such as acetoxy, or lower alkoxycarbonyloxy group, for example a tert-butoxycarbonyloxy group. Preference is given especially to acyl groups Rj of an unsubstituted or substituted amino acid selected from alanyl, N-lower alkylalanyl, such as N-methylalanyl, phenylalanyl, N-(benzyloxycarbonyl)-phenylalanyl, N-(9-fluorenylmethoxycarbonyl)phenylalanyl, aminoacetyl (glycyl), N-lower alkylaminoacetyl, N,N-di-lower alkylaminoacetyl, N-lower alkyl-N-phenyl-lower alkylaminoacetyl, N-lower alkyl-N-imidazolyl-lower alkylaminoacetyl, N-lower alkyl-N-pyridyl-lower alkylaminoacetyl, N-lower alkyl-N-lower alkoxy-carbonylaminoacetyl, N-phenyl-lower alkoxycarbonyl-N-lower alkylaminoacetyl, N-morpholino- or N-thiomorpholino-lower alkylaminoacetyl, for example N-methyl-aminoacetyl, N,N-dimethylaminoacetyl, N-methyl-N-(n-butyl)aminoacetyl, N-methyl-N-benzylaminoacetyl, N-methyl-N-[(2-, 3- or 4-)pyridylmethyl]-aminoacetyl, such as N-methyl-N-(2- or 3-)pyridylmethylaminoacetyl, N-(imidazol-4-ylmethyl)-N-methyl- -17- aminoacetyl, N-methyl-N-tert-'outoxycarbonylaminoacetyl, N-benzyloxycarbonyl-N-lower alkylaminoacetyl, N-morpholinocarbonylaminoacetyl, 3-aminopropionyl, 2-aminobutyryl, 3-aminobutyryl, 4-aminobutyryl, 4-(N,N-dimethylamino)butyryl, 3-aminopentanoyl, 4-aminopentanoyl, 5-aminopentanoyl, 3-aminohexanoyl, 4-aminohexanoyl or 5-amino-hexanoyl, valyl, N-phenylacetyl-valyl, N-acetyl-valyl, N-(3-phenylpropionyl)-valyl, N-(2-, 3- or 4-pyridylcarbonyl)-valyl, N-methoxycarbonyl-valyl, N-isobutoxycarbonyl-valyl, N-tert-butoxycarbonyl-valyl, N-benzyloxycarbonyl-valyl, N-(moipholinocarbonyl)-valyl, norvalyl, leucyl, N-acetyl-leucyl, N-(2-, 3- or 4-pyridylcarbonyl)-leucyl, N- (benzyloxycar-bonyl)-leucyl, isoleucyl, N-acetyl-isoleucyl, N-propionyl-isoleucyl, N-(benzyloxy-carbonyl)-isoleucyl, N-(tert-butoxycarbonyl)-isoleucyl, metMonyl, lysyl, glutamyl, Y-(N-benzyloxycarbonyl)-glutamyl, asparagyl and P-(N-benzyloxycarbonyl)-asparagyl, the amino acid residues preferably being in the (L)- or the (D)- or (D,L)-form (except in cases where there is no asymmetric carbon atom, for example in the case of Gly). In compounds of formula I, if hydroxy or amino groups having a free hydrogen atom are located at a carbon atom from which a double bond originates, for example in the case of substituted lower alkenyl or lower alkynyl, tautomeric forms (resulting from keto/enol tautomerism or imine/enamine tautomerism) are possible. Those and similar tautomers the occurrence of which is familiar to a person skilled in the art are also included within the scope of the present Application. Preferenc e is given to compounds of formula I in which tautomerism in the radical Rj cannot occur (e.g. where there is no bonding of -OH or -NH-to carbon atoms from which a double bond orignates). The compounds mentioned are in all cases adequately stable compounds, and not unstable compounds which will be immediately recognisable to a person skilled in the art. Adequately stable compounds arc especially those compounds that can be isolated, stored and/or processed, for example to form pharmaceutical compositions. Salts of compounds of formula I are especially acid addition salts, salts with bases or, where several salt-forming groups are present, mixed salts or internal salts, as appropriate. Salts are especially the pharmaceutically acceptable, non-toxic salts of compounds of formula I. Such salts are formed, for example, from compounds of formula I having an acid group, for example a carboxy group, and are, for example, salts thereof with suitable bases, such "J V- f'~- <• £ U U 1 -18- as non-toxic metal salts derived from metals of groups la, lb, Ha and lib of the Periodic Table of the Elements, especially suitable alkali metal salts, for example lithium, sodium or potassium salts, or alkaline earth metal salts, for example magnesium or calcium salts, also zinc salts or ammonium salts, as well as salts formed with organic amines, such as unsubstituted or hydroxy-substituted mono-, di- or tri-alkylamines, especially mono-, di-or tri-lower alkylamines, or with quaternary ammonium compounds, for example with N-methyl-N-ethylamine, diethylamine, triethylamine, mono-, bis- or tris-(2-hydroxy-lower alkyl)amines, such as mono-, bis- or tris-(2-hydroxyethyl)amine, 2-hydroxy-tert-butyl-amine or tris(hydroxymethyl)methylamine, NJN-di-lower alkyl-N- (hydroxy-lower alkylamines, such as N,N-dimethyl-N-(2-hydioxyethyl)-amine or tri(2-hydroxyethyl)amine, N-methyl-D-glucamine, or quaternary ammonium salts, such as tetrabutylammonium salts. The compounds of formula I having a basic group, for example a tertiary amino group, can form acid addition salts, for example with inorganic acids, for example a hydrohalic acid, such as hydrochloric acid, sulfuric acid or phosphoric acid, or with organic carboxylic, sulfonic, sulfo or phospho acids or N-substituted sulfamic acids, for example acetic acid, propionic acid, glycolic acid, succinic acid, maleic acid, hydroxy-maleic acid, methylmaleic acid, fumaric acid, malic acid, tartaric acid, gluconic acid, glucaric acid, glucuronic acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, salicylic acid, 4-aminosalicylic acid, 2-phenoxybenzoic acid, 2-acetoxybenzoic acid, embonic acid, nicotinic acid or isonicotinic acid, as well as with amino acids, for example the a-amino acids mentioned hereinbefore, and with methanesulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, ethane-1,2-disulfonic acid, benzenesulfonic acid, 4-methylbenzenesulfonic acid, naphthalene-2-sulfonic acid, 2- or 3-phosphoglycerate, glucose-6-phosphate, N-cyclohexylsulfamic acid (forming cyclamates) or with other acidic organic compounds, such as ascorbic acid. Compounds of formula I having acid and basic groups can also form internal salts. For isolation or purification purposes, it is also possible to use pharmaceutical^ unacceptable salts. The terms "compounds" and "salts" expressly include also individual compounds or individual salts. The compounds of formula I have valuable pharmacological properties. For example, after administration to a warm-blooded animal, such as a human, there are released from those compounds by a metabolic route compounds of formula n which are described as -19- antiretroviral inhibitors of aspartate proteases, such as HIV-protease, and which are suitable especially for the treatment of AIDS as inhibitors of the aspartate proteases of HIV-1 and/or HTV-2 (and possibly other retroviruses that cause symptoms analogous to AIDS) (see EP 0 346 847 (published 19 June 1991) and the other publications referred to above). The binding of a compound of formula H to HIV-1-protease is described, for example, in J. Med. Chem. 34,3340-3342 (1991), and the inhibitory action against HTV-1 and HTV-2-proteases and the antiviral inhibitory action in cell cultures are described in Science 248,358-361 (1990). Action against STV-infected cells is also described (Biochem. Biophys. Res. Commun. 176.180-188 (1991)). The compounds of formula II are released from the compounds of formula I in the body of the animal to be treated, preferably a warm-blooded animal including a human. With the aid of the compounds of formula I it is possible, especially also in the case of enteral, preferably oral, administration of the compounds of formula I, to achieve markedly better absorption of the compound of formula II and/or a higher blood concentration of the compound of formula II than is possible on administration of the compound of formula II itself under otherwise identical conditions. It will also be possible, by means of the introduced radical R1( for example, to influence the distribution of the active ingredient in the body in a beneficial manner. Thus the problem mentioned at the beginning of providing precursors of compounds having antiretroviral action with an improved pharmacodynamic profile for the treatment of retroviral diseases, such as AIDS, is solved by means of the novel compounds of formula L The advantageous pharmacodynamic properties can be demonstrated, for example, as follows: The compounds of formula I to be investigated or, as control, the comparison compound of formula n, are dissolved in dimethyl sulfoxide (DMSO) in a concentration of 240 mg/ml. The resulting solutions are diluted with 20 % (w/v) hydroxypropyl-fi-cyclo-dextrin (HPPCD) to obtain a concentration of the test compound of 12 mg/ml. That solution is administered to mice in a dose of 120 mg/kg by means of artificial special feeding. 30,60,90 and 120 min after administration the animals are sacrificed and blood is removed. Three or four animals are examined per time point The blood is heparinised and prepared for analysis using one of the following two methods: according to the first method, whole blood is deproteinised by mixing one part by volume of blood with one -20- part by volume of acetonitrile; after centrifugation the supernatant is analysed by reversed-phase HPLC. According to the second method, an internal standard is added to the heparinised blood in a final concentration of 4 |xM. The blood is centrifuged. 0.25 ml of plasma is drawn off and deproteinised with an equal volume of acetonitrile. After centrifugation the supernatant is concentrated by drying in vacuo and the residue is suspended in 20 pi of 3M NaCl solution and 100 jd of 0.05M phthalate buffer having a pH of 3.0. The suspension is extracted first with 1 ml, then with 0.2 ml of diisopropyl ether. The diisopropyl ether solution is concentrated to dryness by evaporation and the residue is dissolved in 50 % (v/v) aqueous acetonitrile. The solution is analysed by reversed-phase HPLC. The analysis by reversed-phase HPLC is carried out using a 125 x 4.6 mm Nucleosil® C18-column (reversed-phase material supplied by Macherey-Nagel, Diiren, Federal Republic of Germany, based on silica gel derivatised with hydrocarbon radicals having 18 carbon atoms) equilibrated with a mobile phase of 40 % acetonitrile in water/0.1 % trifluoroacetic acid. The flow rate is 1 ml/min. Detection is effected at 215 nra. Standards for the compounds in blood are worked up analogously to the blood samples and used to establish standard curves on the basis of which the in vivo concentrations are determined. The following results are obtainable from a comparison of the compounds of formula I with those of formula n (active component): the concentration of the active component of formula II in the blood of mice after oral administration of a compound of formula L for example of a compound of formula I wherein R} is acetyl, is at most time points, especially at all the above-mentioned time points, significantly higher, for example more than three times higher, than when the compound of formula II is administered in unesterified form. Alternatively, or in addition, thereto the absorption of the compound of formula 1, for example of the compound of formula I wherein Ri is acetyl, is significantly higher, for example more than four times higher, than the absorption of the compound of formula n. It is also possible over a prolonged period to maintain a higher blood level with a compound of formula I than with the compound of formula II. The compounds of the present invention can also be used as commercially marketable comparison compounds in the testing of other aspartate protease inhibitors, by using them practically as standard compounds in order, for example, to provide for other animal species that are used a measure of the extent to which blood levels obtained are species- 2. J {j Q | y -21- dependent Thus on the one hand a compound not mentioned here can be investigated using the above-mentioned mouse model, and on the other a compound of formula I that is mentioned here can be used as the comparison compound in a comparison with the compound to be investigated in other animal models. In the definitions of compounds of formula I mentioned below, it may be advantageous, for example in order to replace rather general definitions with more specific definitions, to use definitions of radicals from die general definitions given above or to omit individual substituents. Preference is given to compounds of formula 1 wherein is octanoyl, decanoyl, dodecanoyl, palmitoyl, unsubstituted or substituted lower alkanoyl, lower alkenoyl or lower alkynoyl, wherein the substituents are selected from one or more radicals, preferably from up to three radicals, especially from one radical or also two radicals selected from the group consisting of hydroxy, lower alkoxy, lower alkoxy-lower alkoxy, lower alkoxy-lower alkoxy-lower alkoxy, phenoxy, naphthyloxy, phenyl-lower alkoxy, 2-halo-lower alkanoyl, such as 2-chloroacetyl, amino-, lower alkylamino- or di-lower alkylamino-lower alkoxy-2-lower alkanoyl, such as dimethylamino-lower alkoxyacetyl, amino-, lower alkylamino- or di-lower alkylamino-lower alkoxy-lower alkoxy-2-lower alkanoyl, such as dimethylamino-(2-lower alkoxyethoxy)acetyl, lower alkanoyloxy, phenyl-lower alkanoyloxy, such as benzoyloxy or phenylacetoxy, halogen, such as fluorine, chlorine, bromine or iodine, especially fluorine or chlorine, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, such as benzyloxycarbonyl, carbamoyl, lower alkylcarbamoyl, hydroxy-lower alkylcarbamoyl, di-lower alkylcarbamoyl, bis(hydroxy-lower alkyl)carbamoyl, carbamoyl the nitrogen atom of which is a constituent of a 5- to 7-membered heterocyclic ring which may also contain a further hetero atom selected from oxygen, sulfur, nitrogen and lower alkyl-substituted, such as methyl- or ethyl-substituted, nitrogen, for example pyrrolidinocarbonyl, morpholinocarbonyl, thio-morpholinocarbonyl, piperidin-1-ylcarbonyl, piperazin-1-ylcarbonyl or 4-lower alkyl-piperazin- 1-ylcarbonyl, such as 4-methylpiperazin- 1-ylcarbonyl; cyano, oxo, cycloalkyl, for example Q-Cgcycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclo-hexyl, bicycloalkyl, for example Cg-C^bicycloalkyl, such as decahydronaphth-2-yl, endo- or exo-2-norbornyl, bicyclo[2.2.2]oct-2-yl or bicyclo[3.3.1]non-9-yl, tricycloalkyl, for example C^-C^tricycloalkyl, such as 1- or 2-adamantyl, cycloalkenyl, for example C4-Cgcycloalkenyl, such as 1-cyclohexenyl or 1,4-cyclohexadienyl, bicycloalkenyl, for £ U \j 1 -22- example 5-norbornen-2-yl or bicyclo[2.2.2]octen-2-yl, heterocyclyl, which is a saturated, partially saturated or unsaturated ring containing from 5 to 7 ring atoms and up to four heteroatoms independently selected from nitrogen, sulfur and oxygen, preferably 1 or 2 of the mentioned heteroatoms, the ring being present as such or in once benzo-, cyclopenta-, cyclohexa- or cyclohepta-fiised form, heterocyclyl being unsubstituted or substituted especially by lower alkyl, lower alkanoyl, hydroxy, lower alkoxy, phenyl-lower alkoxy, such as benzyloxy, hydroxy-lower alkyl, such as hysroxymethyl, halogen, cyano and/or by trifluoromethyl, for example pyrrolyl, 2,5-dihydropynolyl, furanyl, thienyl, tetrahydrofuranyl, cyclohepta[b]pyrrolyl, pyrrolidinyl, imidazolyl, imidazolidinyl, pyrazolinyl, pyrazolidinyl, triazolyl, such as 1,2,3-, 1,2,4- or 1,3,4-triazolyl, tetrazolyl, such as 1- or 2-tetrazolyl, tetrahydro-oxazolyl, tetrahydro-isoxazolyl, tetrahydro-thiazolyl, tetrahydro-isothiazolyl, indolyl, isoindolyl, quinolyl, isoquinolyl, benzimidazolyl, benzofuranyl, pyridyl, pyiimidinyl, piperidinyl, piperazin- 1-yl, morpholino, thiomorpholino, S,S-dioxothiomoipholino, 1,2-dihydro- or 1,2,3,4-tetrahydro-quinolyl, or 1,2-dihydro- or 1,2,3,4-tetrahydro-isoquinolyl, the said radicals being unsubstituted or substituted as above, especially by lower alkyl, for example as in 4-lower alkylpiperazin- 1-yl, such as 4-methyl- or 4-ethyl-piperazin-1-yl, by lower alkanoyl, for example as in 4-lower alkanoylpiperazin-l-yl, such as 4-acetyl-piperazin-l-yl, or by hydroxy-lower alkyl, for example as in 5-hydroxymethyl-furan-2-yl-carbonyl, and C6-C12aryl, for example phenyl, naphthyl, such as 1- or 2-naphthyl, indanyl, such as 1- or 2-indanyl, indenyl, such as inden-l-yl, or fluorenyl, such as fluoren-9-yl, wherein aryl is unsubstituted or mono- or poly-substituted, preferably mono-substituted, for example, by lowo: alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, such as trifluoromethyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above, especially hetero-cyclylmethyl wherein heterocyclyl is bonded via a ring nitrogen atom, for example piperidinomethyl, piperazin-l-ylmethyl, 4-lower alkyl-piperazin-1-ylmethyl, such as 4-methyl- or4-ethyl-piperazin-l-ylmethyl, 4-lower alkanoyl-piperazin-1 -ylmethyl, such as 4-acetyl-piperazin-1 -ylmethyl, morpholinomethyl or thiomorpholinomethyl, cyano and/or by nitro, especially phenyl substituted in the p-position by one of the mentioned radicals; lower alkoxycarbonyl, for example methoxy-, ethoxy- or tert-lower alkoxy-carbonyl, such as tert-butoxycarbonyl, 2-halo-lower alkoxycarbonyl, for example 2-chloro-, 2-bromo-, -23- 2-iodo- or 2,2,2-trichloro-ethoxycarbonyl; aryl-lower alkoxycarbonyl, for example arylmethoxy-carbonyl, wherein aryl has from 6 to 14 carbon atoms and is unsubstituted or mono- or poly-substituted, preferably mono-substituted, for example, by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, such as trifluoromethyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above as a substituent of lower alkanoyl, especially heterocyclylmethyl wherein heterocyclyl is bonded via a ring nitrogen atom, for example piperidinomethyl, piperazin-l-ylmethyl, 4-lower alkyl-piperazin-1 -ylmethyl, such as 4-methyl- or 4-ethyl-piperazin-1-ylmethyl, 4-lower alkanoyl-piperazin- 1-ylmethyl, such as 4-acetyl-piperazin-1-ylmethyl, morpholinomethyl or thiomorpholinomethyl, cyano and/or by nitro, and is especially phenyl, 1- or 2-naphthyl, fluorenyl, or phenyl mono- or poly-substituted by lower alkyl, for example methyl or tert-butyl, lower alkoxy, for example methoxy, ethoxy or tert-butoxy, hydroxy, halogen, for example fluorine, chlorine or bromine, and/or by nitro, for example phenyl-lower alkoxycarbonyl, such as benzyloxycarbonyl, 4-methoxybenzyloxy-carbonyl, 4-nitrobenzyloxycarbonyl, diphenyl-lower alkoxycarbonyl, such as diphenyl-methoxycarbonyl, di(4-methoxyphenyl)methoxycarbonyl, trityloxycarbonyl, orfluorenyl-lower alkoxycarbonyl, such as 9-fluorenylmethoxycarbonyl; or heterocyclyl-lower alkoxycarbonyl wherein heterocyclyl is as defined above as a substituent of lower alkanoyl, for example furan-2-ylmethoxycarbonyl or pyridin-2-, -3- or -4-ylmethoxycarbonyl; or the residue, bonded via its a- carbonyl group, of an amino acid selected from glycine, alanine, 2-aminobutyric acid, 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, 5-aminopentanoic acid, 3-aminohexanoic acid, 4-aminohexanoic acid, S-aminohexanoic acid, valine, norvaline, leucine, isoleucine, norleucine, serine, homoserine, threonine, methionine, cysteine, phenylalanine, tyrosine, 4-aminophenyl-alanine, 4-chlorophenylalanine, 4-carboxyphenylalanine, (J-phenylserine, phenylglycine, a-naphthylalanine, cyclohexylalanine, cyclohexylglycine, tryptophan, aspartic acid, asparagine, aminomalonic acid, aminomalonic acid monoamide, glutamic acid, glutamine, histidine, arginine, lysine, 5-hydroxylysine, ornithine, 3-aminopropanoic acid, a.y-di-aminobutyric acid and a,P-diaminopropionic acid, especially the residue of an aliphatic amino acid selected from alanine, valine, norvaline, leucine, 3-aminopropionic acid, 2-aminobutyric acid, 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, 5-aminopentanoic acid, 3-aminohexanoic acid, 4-aminohexanoic acid, S-aminohexanoic acid and isoleucine, or of an amino acid selected from glycine, -24- asparagine, glutamine, methionine, lysine and phenylalanine, it being possible for each of the mentioned amino adds to be in the D-, L- or (DJL)-form, preferably in the L-form (except in cases where there is no asymmetric carbon atom, for example in the case of glycine), an a-amino group, if present, is unsubstituted or is mono- or di-N-alkylateJ by lower alkyl, such as methyl, n-propyl or n-butyl, by amino-lower alkyl, such as 3-aminopropyl, by phenyl- or naphthyl-amino-lower alkyl, such as 3-phenylaminopropyl, by phenyl-lower alkyl, such as benzyl, by diphenylmethyl, by trityl, and/or by heterocyclyl-lower alkyl wherein heterocyclyl is as defined above for substituted lower alkanoyl Rj, especially by heterocyclylmethyl, for example furanyl-lower alkyl, such as 2-furylmethyl, thienyl-lower alkyl, such as 2-thicnylmethyl, imidazolyl-lower alkyl, such as imidazol-4-ylmethyl, or 2-, 3- or 4-pyridyl-lower alkyl, such as 2-, 3- or 4-pyridylmethyl, and/or is N-acylated, for example, by the unsubstituted or substituted lower alkanoyl radicals mentioned above in the definition of Rlf especially by acetyl, propionyl, pivaloyl, heterocyclyl-lower alkanoyl, as defined above for substituted lower alkanoyl Rlf for example furan-2-ylcarbonyl, 5 -hydroxymethyl-furan-2-ylcarbonyl, 2-, 3- or 4-pyridylcarbonyl, morpholinocarbonyl, thiomorpholinocarbonyl, indolylacetyl or benzofuranylacetyl, aryl-lower alkanoyl, such as benzoyl or phenylacetyl, lower alkoxycarbonyl, such as tert-butoxycarbonyl, or aryl-lower alkoxycarbonyl, as defined above, for example phenyl-lowt 'koxycarbonyl, such as benzyloxycarbonyl, a carboxy group of the side chain is present in free form, in the form of a lower alkyl ester group, such as methoxycarbonyl or tert-butoxycarbonyl, an aryl ester group or an aryl-lower alkyl ester group, wherein aryl is phenyl, 4-nitrophenyl, naphthyl, fluorenyl or biphenylyl, for example in the form of a 4-nitrpphenoxycarbonyl, benzyloxycarbonyl or 9-fluorenylmethoxycarbonyi group, or in the form of a carbamoyl, a lower alkylcarbamoyl, such as methylcarbamoyl, a di-lower alkylcarbamoyl, such as dimethyl-carbamoyl, a mono- or di-(hydroxy-lower alkyl)carbamoyl, such as hydroxymethyl-carbamoyl or di(hydroxymethyl)carbamoyl group, or a mono- or di-(carboxy-lower alkylcarbamoyl group, such as acarboxymethylcarbamoyl or di(carboxymethyl)carbamoyl group, an amino group of the side chain that is not in the a-position is present in free form, in the form of mono- or di-lower alkylamino, such as n-butylamino or dimethylamino, lower alkanoylamino, such as acetylamino or pivaloylamino, amino-lower alkanoylamino, such as 3-amino-3,3-dimethylpropionylamino, aryl-lower alkanoylamino wherein aryl has from 6 to 14 carbon atoms, for example phenyl, naphthyl or fluorenyl, and is unsubstituted or substituted by lower alkyl, hydroxy, lower alkoxy, carboxy, carbamoyl or by sulfamoyl, * i r: ^ i ^ 0 w Li 1 -25- such as 4-hydroxyphenylbutyryl, lower alkoxycarbonylamino, such as tert-butoxy-carbonylamino, arylmethoxycarbonylamino wherein aryl has from 6 to 14 carbon atoms, such as benzyloxycarbonylamino or 9-fluoienylmethoxycarbonylamino, piperidyl-1-carbonyl, morpholinocarbonyl, thiomorpholinocarbonyl or S,S-dioxothiomorpholino-carbonyl, and/or a hydroxy group of the side chain is present in free form, in the form of a lower alkoxy, such as methoxy or tert-butoxy, phenyl-lower alkoxy, such as benzyloxy, lower alkanoyloxy, such as acetoxy, or lower alkoxycarbonyloxy group, for example a tert-butoxy-carbonyloxy group, and to salts of those compounds, especially pharmaceutically acceptable salts thereof. Preference may also be given to the compounds of formula I, and salts thereof, wherein is aminocarbonyl or an aminocarbonyl radical wherein the amino group carries one or two substituents selected independently of one another from unsubstituted or substituted lower alkyl, the substituents of which are selected from hydroxy, lower alkoxy, phenoxy, naphthyloxy, lower alkanoyloxy, phenyl-lower alkanoyloxy, such as benzoyloxy or phenylacetoxy, halogen, such as fluorine, chlorine, bromine or iodine, especially fluorine or chlorine, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, such as benzyloxycarbonyl, carbamoyl, lower alkylcarbamoyl, hydroxy-lower alkylcarbamoyl, di-lower alkylcarbamoyl, bis(hydroxy-lower alkyl)carbamoyl, cyano, oxo and Cg-C^aryl, for example phenyl, naphthyl, such as 1- or 2-naphthyl, indanyl, such as 1- or 2-indanyl, indenyl, such as inden-l-yl, or fluorenyl, such as fluoren-9-yl, aryl being unsubstituted or mono- or poly-substituted, preferably mono-substituted, for example, by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, such as trifluoromethyl, cyano and/or by nitro, especially phenyl substituted in the p-position by one of the mentioned radicals; especially unsubstituted lower alkyl, such as methyl or ethyl; and aryl which has from 6 to 14 carbon atoms and is unsubstituted or mono- or poly-substituted, preferably mono-substituted, by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, -26- mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, such as trifluoromethyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above as a substituent of lower alkanoyl, especially heterocyclylmethyl wherein heterocyclyl is bonded via a ring nitrogen atom, for example piperidixiomethyl, piperazin- 1-ylmethyl, 4-lower alkyl-piperazin-1 -yl-methyl, such as 4-methyl- or 4-ethyl-piperazin-1-ylmethyl, 4-lower alkanoyl-piper-azin-1-ylmethyl, such as 4-acetyl-piperazin-1 -ylmethyl, morpholinomethyl or thiomorpho-linomethyl, cyano and/or by nitro, preferably correspondingly substituted phenyl or 1- or 2-naphthyl, not more than one of the substituents of the aminocarbonyl radical being aryl; Rj being especially aminocarbonyl, mono- or di-lower alkylaminocarbonyl, such as N-methyl-, N-ethyl-, N,N-dimethyl- or N,N-diethyl-aminocarbonyl, or phenyl-lower alkylaminocarbonyl wherein phenyl is unsubstituted or substituted by the radicals mentioned in the definition of aryl, for example by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl or trifluoromethyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, carboxy and/or by cyano, preferably by up to three of those substituents selected independently of one another, especially by one of those substituents, for example in the p-position, such as in N-benzyl-, N-(4-fluoro-benzyl)-, N-(4-chlorobenzyl)-, N-(4-trifluoromethylbenzy 1)- or N-(4-cyanobenzyl)-amino-carbonyl; especially aminocarbonyl substituted by only one radical at rite nitrogen atom, for example N-lower alkylaminocarbonyl, such as N-methyl- or N-ethyl-aniinocarbonyl, or phenyl-lower alkylaminocarbonyl wherein phenyl is unsubstituted or substituted by the radicals mentioned in the definition of aryl, for example by lower alkyl, such as methyl, halo-lower alkyl, such as chloro- or bromo-methyl or trifluoromethyl, halogen, such as fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, carboxy and/or by cyano, preferably by up to three of those substituents selected independently of one another, especially by one of those substituents, for example in the p-position, such as in N-benzyl-, N-(4-fluorobenzyl)-, N-(4-chlorobenzyl)-, N-(4-trifluaromethylbenzyl)- or N-(4-cyanobenzyl)-aminocarbonyl. Preference is given especially to compounds of formula I wherein is unsubstituted or substituted lower alkanoyl, lower alkenoyl or lower alkynoyl, wherein the substituents are selected from one or more radicals, preferably from up to three radicals, especially from one radical selected from the group consisting of hydroxy, lower alkoxy, phenoxy, naphthyloxy, lower alkanoyloxy, phenyl-lower alkanoyloxy, such as benzoyloxy or phenylacetoxy, halogen, such as fluorine, chlorine, bromine or iodine, especially fluorine or chlorine, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, such as benzyloxycarbonyl, carbamoyl, lower alkylcarbamoyl, lib 00 1 7 -27- hydroxy-lower alkylcarbamoyl, di-lower alkylcarbamoyl, bis(hydroxy-lower alkyl)-carbamoyl, carbamoyl the nitrogen atom of which is a constituent of a S- to 7-membered heterocyclic ring that may also contain a further hetero atom selected from oxygen, sulfur, nitrogen and lower alkyl-substituted, such as methyl- or ethyl-substituted, nitrogen, for example pyrrolidinocarbonyl, morpholinocarbonyl, thiomorpholino-carbonyl, piperidin-1 y^'^bonyl, piperazin- 1-ylcarbonyl or 4-lower alkylpiperazin-1 -yl-caibonyl, such as 4-methylpiperazin-l-ylcarbonyl; cyano, oxo, cycloalkyl, for example C3-C8cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, bicyclo-alkyl, for example Cg-C^bicycloalkyl, such as decahydronaphth-2-yl, endo- or exo-2-noibornyl, bicyclo[2.2.2]oct-2-yl or bicyclo[3.3.1]non-9-yl, tricycloalkyl, for example C9"C14tricycloalkyl, such as 1- or 2-adamantyl, cycloalkenyl, for example C^Cgcyclo-alkenyl, such as 1-cyclohexenyl or 1,4-cyclohexadienyl, bicycloalkenyl, for example 5-norbornen-2-yl or bicyclo[2.2J2]octen-2-yl, heterocyclyl, which is preferably a saturated, partially saturated or unsaturated ring containing from 5 to 7 ring atoms and up to four heteroatoms independently selected from nitrogen, sulfur and oxygen, preferably 1 or 2 of the mentioned heteroatoms, the ring being present as such or in once benzo-, cyclopenta-, cyclohexa- or cyclohepta-fused form, heterocyclyl being unsubstituted or substituted especially by lower alkyl, lower alkanoyl, hydroxy, lower alkoxy, phenyl-lower alkoxy, such as benzyloxy, hydroxy-lower alkyl, such as hysroxymethyl, halogen, cyano and/or by trifluoromethyl, for example pyrrolyl, 2,5-dihydropyrrolyl, furanyl, thienyl, tetrahydrofuranyl, cyclohepta[b]pyrrolyl, pyrrolidinyl, irnidazolyl, imidazolidinyl, pyrazolinyl, pyrr jlidinyl, triazolyl, such as 1,2,3-, 1,2,4- or 1,3,4-triazolyl, tetrazolyl, such as 1- or 2-tetrazolyl, tetrahydro-oxazolyl, tetrahydro-isoxazolyl, tetrahydro-thiazolyl, tetrahydro-isothiazolyl, indolyl, isoindolyl, quinolyl, isoquinolyl, benzimidazolyl, benzofuranyl, pyridyl, pyrimidinyl, piperidinyl, piperazin- 1-yl, morpholino, thiomorpholino, S.S-dioxothiomorpholino, 1,2-dihydro- or 1,2,3,4-tetrahydro-quinolyl, or 1,2-dihydro- or 1,2,3,4-tetrahydro-isoquinolyl, the mentioned radicals being unsubstituted or substituted as above, especially by lower alkyl, for example as in 4-lower alkyl-piperazin-1-yl, such as 4-methyl- or 4-ethyl-piperazin-1-yl, by lower alkanoyl, for example as in 4-lower alkanoyl-piperazin-l-yl, such as 4-acetyl-piperazin-l-yl, or by hydroxy-lower alkyl, for example as in 5-hydroxymethyl-furan-2-yl-carbonyl, and Cg-C^aryl, for example phenyl, naphthyl, such as 1- or 2-naphthyl, indanyl, such as 1- or 2-indanyl, indenyl, such as inden-l-yl, or fluorenyl, such as fluoren-9-yl, wherein aryl is unsubstituted or mono- or poly-substituted, preferably mono-substituted, for example, by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, 250017 -28- hydroxy, lower alkoxy, such as methoxy, Iowa: alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, such as trifluoromethyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above, especially hetero-cyclylmethyl wherein heterocyclyl is bonded via a ring nitrogen atom, for example piperidinomethyl, piperazin-l-ylmethyl, 4-lower alkyl-piperazin-1 -ylmethyl, such as 4-methyl- or 4-ethyl-piperazin-1-ylmethyl, 4-lower alkanoyl-piperazin-l-ylmethyl, such as 4-acetyl-piperazin- 1-ylmethyl, morpholinomethyl or thiomorpholinomethyl, cyano and/or by nitro, especially phenyl substituted in the p-position by one of the mentioned radicals; lower alkoxycarbonyl, for example methoxy-, ethoxy- or tert-lower alkoxy-carbonyl, such as tert-butoxycarbonyl, 2-halo-lower alkoxycarbonyl, for example 2-chloro-, 2-bromo-, 2-iodo- or 2,2,2-trichloro-ethoxycarbonyl; aryl-lower alkoxycarbonyl, for example arylmethoxy-carbonyl, wherein aryl has from 6 to 14 carbon atoms and is unsubstituted or mono- or poly-substituted, preferably mono-substituted, for example, by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, such as trifluoromethyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above as a substituent of lower alkanoyl, especially heterocyclylmethyl wherein heterocyclyl is bonded via a ring nitrogen atom, for example piperidinomethyl, piperazin-l-ylmethyl, 4-lower alkyl-piperazin-1 -ylmethyl, such as 4-methyl- or 4-ethyl-piperazin-1-ylmethyl, 4-lower alkanoyl-piperazin-l-ylmethyl, such as 4-acetyl-piperazin-1 -ylmethyl, morpholinomethyl or thiomorpholinomethyl, cyano and/or by nitro, and is especially phenyl, 1- or 2-naphthyl, fluorenyl, or phenyl mono- or poly-substituted by lower alkyl, for example methyl or tert-butyl, lower alkoxy, for example methoxy, ethoxy or tert-butoxy, hydroxy, halogen, for example fluorine, chlorine or bromine, and/or by nitro, for example phenyl-lower alkoxycarbonyl, such as benzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 4-nitro-benzyloxycarbonyl, diphenyl-lower alkoxycarbonyl, such as diphenylmethoxycarbonyl, di(4-methoxyphenyl)methoxycarbonyl, trityloxycarbonyl, or fluorenyl-lower alkoxycarbonyl, such as 9-fluorenylmethoxycarbonyl; or heterocyclyl-lower alkoxycarbonyl wherein heterocyclyl is as defined above as a substituent of lower alkanoyl, for example furan-2-ylmethoxycarbonyl or pyridin-2-, -3- or -4-ylmethoxycarbonyl; or the residue, bonded via its a-carbonyl group, of an amino acid selected from glycine, alanine, 2-aminobutyric acid, 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, sj \J {) L -29- 4-aminopentanoic acid, 5-aminopentanoic acid, 3-aminohexanoic acid, 4-aminohexanoic acid, 5-aminohexanoic acid, valine, norvaline, leucine, isoleucine, norleucine, serine, homoserine, threonine, methionine, cysteine, phenylalanine, tyrosine, 4-aminophenyl-alanine, 4-chlcrophenylalanine, 4-carboxyphenylalanine, P-phenylserine, phenylglycine, a-naphthylalanine, cyclohexylalanine, cyclohexylglycine, tryptophan, aspartic acid, asparagine, aminomalonic acid, aminomalonic acid monoamide, glutamic acid, glutamine, histidine, arginine, lysine, 5-hydroxylysine, ornithine, 3-aminopropanoic acid, a/y-di-aminobutyric acid and <x,P-diaminopropionic acid, especially the residue of an aliphatic amino acid selected from alanine, valine, norvaline, leucine, 3-aminopropionic acid, 2-aminobutyric acid, 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, 5-aminopentanoic acid, 3-aminohexanoic acid, 4-aminohexanoic acid, 5-aminohexanoic acid and isoleucine, or of an amino acid selected from glycine, asparagine, glutamine, methionine, lysine and phenylalanine, it being possible for each of the mentioned amino acids to be in the D-, L- or (DJL)-form, preferably in the L-form (except in cases where there is no asymmetric carbon atom, for example in the case of glycine), an a-amino group, if present, is unsubstituted or is mono- or di-N-alkylated by lower alkyl, such as methyl, n-propyl or n-butyl, by amino-lower alkyl, such as 3-aminopropyl, by phenyl- or naphthyl-amino-lower alkyl, such as 3-phenylaminopropyl, by phenyl-lower alkyl, such as benzyl, by diphenylmethyl, by trityl and/or by heterocyclyl-lower alkyl wherein heterocyclyl is as defined above for substituted lower alkanoyl Rj, especially by heterocyclylmethyl, for example furanyl-lower alkyl, such as 2-furylmethyl, thienyl-lower alkyl, such as 2-thienylmethyl, or 2-, 3- or 4-pyridyl-lower alkyl, such as 2-, 3- or 4-pyridylmethyl, and/or is N-acylated, for example, by the unsubstituted or substituted lower alkanoyl radicals mentioned above in the definition of Rlt especially by acetyl, propionyl, pivaloyl, heterocyclyl-lower alkanoyl, as defined above for substituted lower alkanoyl Rx, for example furan-2-ylcarbonyl, 5-hydroxymethyl-furan-2-ylcarbonyl, 2-, 3-or 4-pyridylcarbonyl, morpholinocarbonyl, thiomorpholinocarbonyl, indolylacetyl or benzofuranylacetyl, aryl-lower alkanoyl, such as benzoyl or phenylacetyl, lower alkoxycarbonyl, such as tert-butoxycarbonyl, or aryl-lower alkoxycarbonyl as defined above, for example phenyl-lower alkoxycarbonyl, such as benzyloxycarbonyl, a carboxy group of the side chain is present in free form, in ti e form of a lower alkyl ester group, such as methoxycarbonyl or tert-butoxycarbonyl, an aiyl ester group or an aryl-lower alkyl ester group, wherein aryl is phenyl, 4-nitrophenyl, naphthyl, fluorenyl or biphenylyl, for example in the form of a 4-nitrophenoxycarbonyl, benzyloxycarbonyl or 9-fluorenylmethoxycarbonyl group, or in the form of a carbamoyl, a lower alkyl- -30- carbamoyl, such as methylcarbamoyl, a di-lower alkylcarbamoyl, such as dimethyl-carbamoyl, a mono- or di-(hydroxy-lower alkyl)carbamoyl, such as hydroxymethyl-carbamoyl or di(hydroxym.ethyl)carbamoyl, or a mono- or di-(carboxy-lower alkylcarbamoyl group, such as a carboxymethylcaibamoyl or di(carboxymethyl)carbamoyl group, an amino group of the side chain that is not in the a-position is present in free form, in the form of mono- or di-lower alkylamino, such as n-butylamino or dimethylamino, lower alkanoylamino, such as acetylamino or pivaloylamino, amino-lower alkanoylamino, such as 3-amino-3,3-dimethylpropionylamino, aryl-lower alkanoylamino wherein aryl has from 6 to 14 carbon atoms, for example phenyl, naphthyl or fluorenyl, and is unsubstituted or substituted by lower alkyl, hydroxy, lower alkoxy, carboxy, carbamoyl or by sulfamoyl, such as 4-hydroxyphenylbutyryl, lower alkoxycarbonylamino, such as tert-butoxy-carbonylamino, arylmethoxycarbonylamino wherein aryl has from 6 to 14 carbon atoms, such as benzyloxycarbonylamino or 9-fluorenylmethoxycaibonylamino, piperidyl-1-carbonyl, morpholinocarbonyl, thiomorpholinocarbonyl or S ,S-dioxothiomorpholino-carbonyl, and/or a hydroxy group of the side chain is present in free form or in the form of a lower alkoxy, such as methoxy or tert-butoxy, phenyl-lower alkoxy, such as benzyloxy, lower alkanoyloxy, such as acetoxy, or lower alkoxycarbonyloxy group, for example a tert-butoxycarbonyloxy group, and to salts of those compound*, especially pharmaceutically acceptable salts thereof. Preference may also be given to the compounds of formula I, and salts thereof, wherein Rj is aminocarbonyl or an aminocarbonyl radical wherein the amino group carries one or two substituents selected independently of one another from unsubstituted or substituted lower alkyl, the substituents of which are selected from hydroxy, lower alkoxy, phenoxy, naphthyloxy, lower alkanoyloxy, phenyl-lower alkanoyloxy, such as benzoyloxy or phenylacetoxy, halogen, such as fluorine, chlorine, bromine or iodine, especially fluorine or chlorine, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, such as benzyloxycarbonyl, carbamoyl, lower alkylcarbamoyl, hydroxy-lower alkylcarbamoyl, di-lower alkylcarbamoyl, bis(hydroxy-lower alkyl)carbamoyl, cyano, oxo and C6-C12aryl, for example phenyl, naphthyl, such as 1- or 2-naphthyl, indanyl, such as 1- or 2-indanyl, indenyl, such as inden-l-yl, or fluorenyl, such as fluoren-9-yl, aryl being unsubstituted or mono- or poly-substituted, preferably mono-substituted, for example, by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower 25 0 0 1 j -31- alkoxy, such as methoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, such as trifluoromethyl, cyano and/or by nitro, especially phenyl substituted in the p-position by one of the mentioned radicals; especially unsubstituted lower alkyl, such as methyl or ethyl; and from aryl which has from 6 to 14 carbon atoms and is unsubstituted or mono- or poly-substituted, preferably mono-substituted, by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, such as trifluoromethyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above as a substituent of lower alkanoyl, especially heterocyclylmethyl wherein heterocyclyl is bonded via a ring nitrogen atom, for example piperidinomethyl, piperazin-l-ylmethyl, 4-lower aikyIpiperazin- 1-ylmethyl, such as 4-methyl- or4-ethyl-piperazin-l-ylmethyl, 4-lower alkanoyl-piperazin-l-ylmethyl, such as 4-acetyl-piperazin-1 -ylmethyl, morpholinomethyl or thiomorpholinomethyl, cyano and/or by nitro, preferably correspondingly substituted phenyl or 1- or 2-naphthyl, not more than one of the substituents of the aminocarbonyl radical being aryl; especially aminocarbonyl, mono- or di-lower alkylaminocarbonyl, such as N-methyl-, N-ethyl-, N,N-dimethyl- or N,N-diethyl-aminocarbonyl, or phenyl-lower alkylaminocarbonyl wherein phenyl is unsubstituted or substituted by the radicals mentioned in the definition of aryl, for example by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl or trifluoromethyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, carboxy and/or by cyano, pi durably by up to three of those substituents selected independently of one another, especially by one of those substituents, for example in the p-position, such as in N-benzyl-, N-(4-fluoro-benzyl)-, N-(4-chlorobenzyl)-, N-(4-trifluoromethylbenzyl)- orN-(4-cyanobenzyl)-amino-carbonyl; especially aminocarbonyl substituted by only one radical at the nitrogen atom, for example N-lower alkylaminocarbonyl, such as N-methyl- or N-ethyl-aminocarbonyl, or phenyl-lower alkylaminocarbonyl wherein phenyl is unsubstituted or substituted by the radicals mentioned in the definition of aryl, for example by lower alkyl, such as methyl, halo-lower alkyl, such as chloro- or bromo-methyl or trifluoromethyl, halogen, such as fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, carboxy and/or by cyano, preferably by up to three of those substituents selected independently of one another, especially by one of those substituents, for example in the p-position, such as in 15 0 0 1 7 -32- N-benzyl-, N-(4-fluorobenzyl)-, N-(4-chlorobenzyl)-, N-(4-trifIi! "romethylbenzy 1)- or N- (4-cyanobenzyl)-aminocarbonyl. Greater preference is given to compounds of formula I wherein Rj is octanoyl, decanoyl, dodecanoyl, palmitoyl, unsubstituted or substituted lower alkanoyl, wherein the substituents are selected from one to three radicals, especially from one radical or also two radicals selected from the group consisting of hydroxy, lower alkoxy, lower alkoxy-lower alkoxy, lower alkoxy-lower alkoxy-lower alkoxy, phenoxy, naphthyloxy, phenyl-lower alkoxy, 2-halo-lower alkanoyl, such as 2-chloroacetyL, amino-, lower alkylamino- or di-lower alkylamino-lower alkoxy-2-lower alkanoyl, such as dimethylamino-lower alkoxyacetyl, amino-, lower alkylamino- or di-lower alkyl-amino-lower alkoxy-lower alkoxy-2-lower alkanoyl, such as dime thylamino- (2-lower alkoxyethoxy)acetyl, lower alkanoyloxy, phenyl-lower alkanoyloxy, such as benoyloxy or phenylacetoxy, halogen, such as fluorine, chlorine, bromine or iodine, especially fluorine or chlorine, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, such as benzyloxycarbonyl, carbamoyl, lower alkylcarbamoyl, hydroxy-lower alkylcarbamoyl, di-lower alkylcarbamoyl, bis(hydroxy-lower alkylcarbamoyl, cyano, oxo, C3-Cgcycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, C4-Cgcycloalkenyl, such as 1-cyclohexenyl or 1,4-cyclohexadienyl, pyrrolyl, 2,5-di-hydropyrrolyl, furanyl, thienyl, tetrahydrofuranyl, pyrrolidinyl, imidazolyl, imidazo-lidinyl, pyrazolyl, pyrazolidinyl, tetrahydro-oxazolyl, tetrahydro-isoxazolyl, tetrahydro-thiazolyl, tetrahydro-isothiazolyl, indolyl, isoindolyl, quinolyl, isoquinolyl, benzimidazolyl, benzofuranyl, pyridyl, pyiimidinyl, piperidinyl, piperazin-l-yl, mor-pholino, thiomorpholino, S,S-dioxothiomorpholino, 1,2-dihydro- or 1,2,3,4-tetrahydro-quinolyl or 1,2-dihydro- or 1,2,3,4-tetrahydio-isoquinolyl, the said heterocyclic radicals being unsubstituted or substituted by lower alkyl, lower alkanoyl, hydroxy, lower alkoxy, phenyl-lower alkoxy, such as benzyloxy, hydroxy-lower alkyl, such as hydroxymethyl, halogen, cyano and/or by trifluoromethyl, especially by lower alkyl, for example as in 4-lower alkyl-piperazin-1-yl, such as 4-methyl- or 4-ethyl-piperazin-1-yl, by lower alkanoyl, for example as in 4-lower alkanoyl-piperazin-l-yl, such as 4-acetyl-piper-azin- 1-yl, or by hydroxy-lower alkyl, for example as in 5-hydroxymethyl-furan-2-yl-caibonyl, and aryl selected from phenyl, naphthyl, such as 1- or 2-naphthyl, indanyl, such as 1- or 2-indanyl, indenyl, such as inden-l-yl, and fluorenyl, such as fluoren-9-yl, those radicals being unsubstituted or mono- or poly-substituted, preferably mono-substituted, for example, by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower -33- alkoxy, such as methoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, such as trifluoromethyl, piperidinomethyl, piperazin-l-ylmethyl, 4-lower alkyl-piperazin-1-ylmethyl, such as 4-methyl- or 4-ethyl-piperazin-l-ylmethyl, 4-lower alkanoyl-piperazin-l-ylmethyl, such as 4-acetyl-piperazin-1-ylmethyl, moipholinomethyl, thiomorpholinomethyl, cyano and/or by nitro, especially phenyl substituted in the p-position by one of the mentioned radicals; or the residue, bonded via its a-carbonyl group, of an amino acid selected from glycine, alanine, 2-aminobutyric acid, 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, S-aminopentanoic acid, 3-aminohexanoic acid, 4-aminohexanoic acid, 5-aminohexanoic acid, valine, norvaline, leucine, isoleucine, norleucine, serine, homoserine, threonine, methionine, cysteine, phenylalanine, tyrosine, 4-amino-phenylalanine, 4-chiorophenylalanine, 4-carboxyphenylalanine, j}-phenylserine, phenyl-glycine, a-naphthylalanine, cyclohexylalanine, cyclohexylglycine, tryptophan, aspartic acid, asparagine, aminomalonic acid, aminomalonic acid monoamide, glutamic acid, glutamine, histidine, arginine, lysine, 5-hydroxylysine, ornithine, 3-aminopropanoic acid, a/y-diaminobutyric acid and a,fJ-diaminopropionic acid, especially the residue of an aliphatic amino acid selected from alanine, valine, norvaline, leucine, 3-aminopropionic acid, 2-aminobutyric acid and isoleucine or of an amino acid selected from glycine, asparagine, glutamine, methionine, lysine and phenylalanine, or of an amino acid selected from 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, S-aminopentanoic acid, 3-aminohexanoic acid, 4-aminohexanoic acid and 5-amino-hexanoic acid, it being possible in all cases for each of the mentioned amino acids to be in the D-, L- or (D,L)-form, preferably in the L-form (except in cases where there is no asymmetric carbon mom, for example in the case of glycine), an a-amino group, if present, is unsubstituted or is mono- or di-N-alkylated by lower alkyl, such as methyl, n-propyl or n-butyl, by amino-lower alkyl, such as 3-aminopropyl, by phenyl- or naphthyl-amino-lower alkyl, such as 3-phenylaminopropyl, by phenyl-lower alkyl, such as benzyl, by diphenylmethyl, by trityl, by furanyl-lower alkyl, such as 2-furyl-methyl, by thienyl-lower alkyl, such as 2-thienylmethyl, by imidazolyl-lower alkyl, such as imidazol-4-ylmethyl, and/or by 2-, 3- or 4-pyridyl-lower alkyl, such as 2-, 3- or 4-pyridylmethyl, and/or is N-acylated by the unsubstituted or substituted lower alkanoyl radicals mentioned above in the definition of Rj, especially by acetyl, propionyl, pivaloyl, furan-2-ylcarbonyl, 5-hydroxymethyl-furan-2-ylcarbonyl, 2-, 3- or 4-pyridylcarbonyl, morpholinocarbonyl, thiomorpholinocarbonyl, indolylacetyl or benzofuranylacetyl, phenyl-lower alkanoyl, such as benzoyl or phenylacetyl, lower alkoxycarbonyl, such as 25 0 0 1 -34- tert-butoxycarbonyl, or phenyl-lower alkoxycarbonyl, such as benzyloxycarbonyl, and to pharmaceutical^ acceptable salts thereof. Greater preference may also be given to the compounds of formula I and the salts thereof wherein Rx is aminocarbonyl, mono- or di-lower alkylaminocarbonyl, such as N-methyl-, N-ethyl-, N,N-dimethyl- or N,N-diethyl-aminocarbonyl, preferably mono-lower alkylaminocarbonyl, or phenyl-lower alkylaminocarbonyl wherein phenyl is unsubstituted or substituted by the radicals mentioned in the definition of aryl, for example by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl or trifluoromethyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, carboxy and/or by cyano, preferably by up to three of those substituents selected independently of one another, especially one of those substituents, for example in the p-position, such as in N-benzyl-, N-(4-fluorobenzyl)-, N- (4-chlorobenzy 1) N-(4-trifluoromethylbenzyl)- or N-(4-cyano-benzyl)-aminocarbonyl. Preference is given more especially to compounds of formula I wherein Rx is unsubstituted or substituted lower alkanoyl, wherein the substituents are selected from one to three radicals, especially from one radical selected from the group consisting of hydroxy, lower alkoxy, phenoxy, naphthyloxy, lower alkanoyloxy, phenyl-lower alkanoyloxy, such as benzoyloxy or phenylacetoxy, halogen, such as fluorine, chlorine, bromine or iodine, especially fluorine or chlorine, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, such as benzyloxycarbonyl, carbamoyl, lower alkylcarbamoyl, hydroxy-lower alkylcarbamoyl, di-lower alkylcarbamoyl, bis(hydroxy-lower alkylcarbamoyl, cyano, oxo, C3-C8cyclo-alkyl, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, C4-Cgcycloalkenyl, such as 1-cyclohexenyl or 1,4-cyclohexadienyl, pyrrolyl, 2,5-dihydropyrrolyl, furanyl, thienyl, tetrahydrofuranyl, pyrrolidinyl, imidazolyl, imidazolidinyl, pyrazolinyl, pyrazol-idinyl, tetrahydro-oxazolyl, tetrahydro-isoxazolyl, tetrahydro- thiazolyl, tetrahydro-isothiazolyl, indolyl, isoindolyl, quinolyl, isoquinolyl, benzimidazolyl, benzofuranyl, pyridyl, pyiimidinyl, piperidinyl, piperazin-l-yl, morpholino, thiomoipholino, S,S-dioxothiomoipholino, 1,2-dihydro- or 1,2,3,4-tetrahydro-quinolyl or 1,2-dihydro- or 1,? 3,4-tetrahydro-isoquinolyl, the said heterocyclic radicals being unsubstituted or substituted by lower alkyl, lower alkanoyl, hydroxy, lower alkoxy, phenyl-lower alkoxy, such as benzyloxy, hydroxy-lower alkyl, such as hydroxymethyl, halogen, cyano and/or by trifluoromethyl, especially by lower alkyl, for example as in 4-lower alkyl-piperazin-1-yl, such as 4-methyl- or 4-ethyl-piperazin-1-yl, by lower alkanoyl, for example as in 4-lower alkanoyl-piperazin-l-yl, such as 4-acetyl-piperazin-1-yl, or by hydroxy-lower -35- alkyl, for example as in 5-hydroxymethyl-furan-2-ylcarbonyl, and aryl selected from phenyl, naphthyl, such as 1- or 2-naphthyl, indanyl, such as 1- or 2-indanyl, indenyl, such as inden-l-yl, and fluorenyl, such as fluoren-9-yl, those radicals being unsubstituted or mono- or poly-substituted, preferably mono-substituted, for example, by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, such as trifluoromethyl, piperidinomethyl, piperazin-l-ylmethyl, 4-lower alkyl-piperazin-1-ylmethyl, such as 4-methyl- or 4-ethyl-piperazin-1-ylmethyl, 4-lower alkanoyl-piperazin-l-ylmethyl, such as 4-acetyl-piperazin-1 -ylmethyl, morpholinomethyl, thiomorpholinomethyl, cyano and/or by nitro, especially phenyl substituted in the p-position by one of the mentioned radicals; or the residue, bonded via its a-carbonyl group, of an amino acid selected from glycine, alanine, 2-aminobutyric acid, 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, 5-aminopentanoic acid, 3-aminohexanoic acid, 4-aminohexanoic acid, 5-aminohexanoic acid, valine, norvaline, leucine, isoleucine, norleucine, serine, homoserine, threonine, methionine, cysteine, phenylalanine, tyrosine, 4-amino-phenylalanine, 4-chlorophenylalanine, 4-carboxyphenylalanine, {3-phenylserine, phenyl-glycine, a-naphthylalanine, cyclohexylalanine, cyclohexylglycine, tryptophan, aspartic acid, asparagine, aminomalonic acid, aminomalonic acid monoamide, glutamic acid, glutamine, histidine, arginine, lysine, 5-hydroxylysine, ornithine, 3-aminopropanoic acid, a,7-diaminobutyric acid and a,p-diaminopropionic acid, especially the residue of an aliphatic amino acid selected from alanine, valine, norvaline, leucine, 3-aminopropionic acid, 2-aminobutyric acid and isoleucine or of an amino acid selected from glycine, asparagine, glutamine, methionine, lysine and phenylalanine, or of an amino acid selected from 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, 5-aminopentanoic acid, 3-aminohexanoic acid, 4-aminohexanoic acid and 5-aminohexanoic acid, it being possible in all cases for each of the mentioned amino acids to be in the D-, L- or (D,L)-form, preferably in the L-form (except in cases where there is no asymmetric carbon atom, for example in the case of glycine), an a-amino group, if present, is unsubstituted or is mono- or di-N-alkylated by lower alkyl, such as methyl, n-propyl or n-butyl, by amino-lower alkyl, such as 3-aminopropyl, by phenyl- or naphthyl-amino-lower alkyl, such as 3-phenylaminopropyl, by phenyl-lower alkyl, such as benzyl, by diphenylmethyl, by trityl, by furanyl-lower alkyl, such as 2-furyl-methyl, by thienyl-lower alkyl, such as 2-thienylmethyl, and/or by 2-, 3- or 4-pyridyl- -36- lower alkyl, such as 2-, 3- or 4-pyridylmethyl, and/or is N-acylated by the unsubstituted or substituted lower alkanoyl radicals mentioned above in the definition of Rj, especially by acetyl, propionyl, pivaloyl, furan-2-ylcarbonyl, 5-hydroxymethyl-furan-2-ylcarbonyl, 2-, 3- or 4-pyridylcarbonyl, morpholinocarbonyl, thiomorpholinocarbonyl, indolylacetyl or benzofuranylacetyl, phenyl-lower alkanoyl, such as benzoyl or phenylacetyl, lower alkoxycarbonyl, such as tert-butoxycarbonyl, or phenyl-lower alkoxycarbonyl, such as benzyloxycarbonyl, and to pharmaceutically acceptable salts thereof. Special preference may also be given to the compounds of formula I and salts thereof wherein Rx is aminocarbonyl, mono- or di-lower alkylaminocarbonyl, such as N-methyl-, N-ethyl-, N,N-di-methyl- or N,N-diethyl-aminocarbonyl, preferably mono-lower alkylaminocarbonyl, or phenyl-lower alkylaminocarbonyl wherein phenyl is unsubstituted or substituted by the radicals mentioned in the definition of aryl, for example by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl or trifluoromethyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, carboxy and/or by cyano, preferably by up to three of those substituents selected independently of one another, especially one of those substituents, for example in the p-position, such as in N-benzyl-, N-(4-fluorobenzyl) -, N-(4-chlorobenzyl)-, N-(4-trifluoromethylbenzyl)- or N-(4-cyanobenzyl)-aminocarbonyl. Still greater preference is given to compounds of formula I wherein Rj is octanoyl, decanoyl, dodecanoyl, palmitoyl, lower alkanoyl, such as formyl, acetyl, propionyl, butyryl, methylpropionyl, n-pentanoyl, pivaloyl, hexanoyl or heptanoyl, hydroxy-lower alkanoyl, for example fi-hydroxypropionyl, lower alkoxy-lower alkanoyl, for example lower alkoxyacetyl or lower alkoxypropionyl, such as methoxyacetyl, 3-methoxypropionyl or n-butoxyacetyl, lower alkoxy-lower alkoxy-lower alkanoyl, such as 2-(2-methoxy-ethoxy)acetyl, lower alkoxy-lower alkoxy-lower alkoxy-lower alkanoyl, such as 2-(2-(2-methoxyethoxy)ethoxy)acetyl, phenoxy-lower alkanoyl, for example phenoxy-acetyl, phenyl-lower alkoxy-lower alkanoyl, such as benzyloxyacetyl, 2-halo-lower alkanoyl, such as 2-chloroacetyl, amino-, lower alkylamino- or di-lower alkylamino-lower alkoxy-2-lower alkanoyl, such as dimethylamino-lower alkoxyacetyl, amino-, lower alkyl-amino- or di-lower alkylamino-lower alkoxy-lower alkoxy-2-lower alkanoyl, such as dimethylamino-(2-lower alkoxyethoxy)acetyl, lower alkanoyloxy-lower alkanoyl, for example lower alkanoyloxy acetyl or lower alkanoyloxypropionyl, such as acetoxyacetyl or P-acetoxypropionyl, car boxy-lower alkanoyl, such as carboxy acetyl or 3-carboxy-propionyl, oxo-lower alkanoyl, for example acetoacetyl or propionylacetyl, 5-hydroxy-methyl-furan-2-ylcarbonyl, 2- or 3-pyrrolylcarbonyl, furylcarbonyl, for example 2-furyl- -37- carbonyl, thienylcarbonyl, for example 2-thienylcaibonyl, pyridyl-lower alkanoyl, such as pyridylcarbonyl, for example 2-, 3- or 4-pyridylcarbonyl, pyridylacetyl, for example 2-pyridylacetyl, or pyridylpropionyl, for example 3-(2-pyridyl)propionyl, quinolyl-carbonyl, such as quinolin-2-ylcarbonyl, isoquinolinylcarbonyl, such as isoquinolin- 3-ylcarbonyl, 2-, 3- or 5-mdolylcarbonyl, pyrrolidinyl-(2- or 3-)carbonyl, 2-, 3- or 4-piperidinylcaibonyl, l,2,3,4-tetrahydroquinolyl-2-, -3- or -4-caibonyl, 1,2,3,4-tetra-hydroisoquinolyl-1-, -3- or -4-carbonyl, imidazolyl-lower alkanoyl, such as imidazolyl-carbonyl, for example imidazol-1 -ylcarbonyl or imidazol-4-ylcarbonyl, imidazolylacetyl, for example 4-imidazolylacetyl, or imidazolylpropionyl, for example 3-(4-imidazolyl)-propionyl, pyrazolyl-lower alkanoyl, such as 1-pyrazolylcarbonyl, morpholinocarbonyl, thiomorpholinocarbonyl, morpholinoacetyl, thiomorpholinoacetyl, 4-lower alkyl-1-piper-azinoacetyl, such as 4-methylpiperazinoacetyl, indolylacetyl, benzofuranylacetyl, phenyl-lower alkanoyl, for example benzoyl, phenylacetyl or 3-phenylpropionyl, that is unsubstituted or mono- or poly-substituted in the phenyl radical by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, for example methoxy, piperidinomethyl, piperazin-l-ylmethyl, 4-lower alkyl-piperazin-1-ylmethyl, such as 4-methyl- or 4-ethyl-piperazin- 1 -ylmethyl, morpholinomethyl, thiomorpholinomethyl, cyano and/or by nitro, for example 4-chloromethy 1-, 4-bromomethyl-, 4-fluoro-, 4-chloro-, 4-methoxy-, 4-morpholinomethyl-, 4-thiomorpholinomethyl-, 4-cyano- or 4-nitro-benzoyl, 4-methyl-phenylacetyl, 4-methoxyphenylacetyl, 3-(p-hydroxyphenyl)-propionyl or 2-lower alkoxy-2-phenylacetyl, such as (R)- or (S)-2-methoxy-2-phenylacetyl; or is the residue, bonded via thea-carbonyl group, of an aliphatic amino acid selected from alanine, valine, norvaline, leucine, 3-aminopropionic acid, 2-aminobutyric acid and isoleucine or of an amino acid selected from glycine, asparagine, glutamine, methionine, lysine and phenylalanine, or of an amino acid selected from 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, 5-aminopentanoic acid, 3-aminohexanoic acid, 4-aminohexanoic acid and 5-aminohexanoic acid, it being possible for each of the mentioned amino acids to be in the D-, L- or (D,L)-form, preferably in the L-form (except where there are no asymmetric carbon atoms, for example in the case of glycine); an a-amino group, if present, is unsubstituted or is mono- or di-N-alkylated by lower alkyl, such as methyl, n-propyl or n-butyl, by phenyl-lower alkyl, such as benzyl, by imidazolyl-lower alkyl, such as imidazol-4-ylmethyl, and/or by 2-, 3- or 4-pyridyl-lower alkyl, such as 2-, 3- or 4-pyridylmethyl, and/or is N-acylated by lower alkoxycarbonyl, such as tert-butoxycarbonyl, or by benzyloxycarbonyl, for example as in alanyl, N-lower alkylalanyl, such as N-methylalanyl, phenylalanyl, aminoacetyl (glycyl), N-lower alkyl- -38- aminoacetyl or N,N-di-lower alkylaminoacetyl, such as N-methylaminoacetyl, N,N-dimethylaminoacetyl or N-methyl-N-(n-butyl)aminoacetyl, N-lower alkyl-N-phenyl-lower alkylaminoacetyl, such as N-methyl-N-benzylaminoacetyl, N-lower alkyl-N-pyridyl-lower alkylaminoacetyl, for example N-methyl-N-[(2-, 3- or 4-)pyridyl-methyl]-aminoacetyl, such as N-methyl-N-(2- or 3-pyridylmethyl)aminoacetyl, N- (imidazolyl-lower alkyl)-N-lower alkylaminoacetyl, such as N-(imidazol-4-yl-methyl)-N -methylaminoacetyl, N-phenyl-lower alkoxy c axbonyl-N -lower alkylaminoacetyl, such as N-benzyloxycarbonyl-N-methylaminoacetyl, 2-aminobutyryl, 4-(N,N-dimethylamino)butyryl, valyl, norvalyl, leucyl, isoleucyl, methionyl, lysyl, glutamyl or asparagyl, wherein the amino acid residues (with the exception of glycine) are preferably in the (L)-form, and to pharmaceutically acceptable salts thereof. Greater preference may also be given to the compounds of formula I and salts thereof wherein is aminocarbonyl, mono- or di-lower alkylaminocarbonyl, such as N-methyl-, N-ethyl-, N,N-dimethyl- or N,N-diethyl-aminocarbonyl, preferably mono-lower alkylaminocarbonyl, or phenyl-lower alkylaminocarbonyl wherein phenyl is unsubstituted or substituted by the radicals mentioned in the definition of aryl, for example by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl or trifluoromethyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, carboxy and/or by cyano, preferably by up to three of those substituents selected independently of one another, especially by one of those substituents, for example in the p-position, such as in N-benzyl-, N-(4-fluorobenzyl)-, N-(4-chlorobenzyl)-, N-(4-trifluoro-methylbenzyl)- or N-(4-cyanobenzyl)-aminocarbonyl. Still greater preference is given especially to compounds of formula 1 wherein Rx is lower alkanoyl, such as acetyl, propionyl, butyryl, pivaloyl, hexanoyl or heptanoyl, hydroxy-lower alkanoyl, for example fi-hydroxypropionyl, lower alkoxy-lower alkanoyl, for example lower alkoxyacetyl or lower alkoxypropionyl, such as methoxyacetyl or fj-methoxypropionyl, phenoxy-lower alkanoyl, for example phenoxyacetyl, lower alkanoyloxy-lower alkanoyl, for example lower alkanoyloxyacetyl or lower alkanoyloxy-propionyl, such as acetoxyacetyl or (5-acetoxypropionyl, oxo-lower alkanoyl, for example acetoacetyl or propionylacetyl, 5-hydroxymethyl-furan-2-ylcarbonyl, 2- or 3-pyrrolyl-carbonyl, furylcarbonyl, for example 2-furylcarbonyl, thienylcarbonyl, for example 2-thienylcarbonyl, pyridylcarbonyl, for example 2-, 3- or 4-pyridylcarbonyl, 2-, 3- or 5-indolylcarbonyl, pyrrolidinyl-3-carbonyl, 2-, 3- or 4-piperidinylcarbonyl, 1,2,3,4-tetra-hydroquinolyl-2-, -3- or -4-carbonyl, 1,2,3,4-tetrahydroisoquinolyl-1 -3- or -4-carbonyl, imidazolylcarbonyl, such as imidazol-1 -ylcarbonyl, morpholinocarbonyl, thiomorpholino- £ V \J u -39- carbonyl, morpholinoacetyl, thiomorpholinoacetyl, 4-lower alkyl- 1-piperazinoacetyl, such as 4-methyl-piperazinoacetyl, indolylacetyl, benzofuranylacetyl, phenyl-lower alkanoyl, for example benzoyl, phenylacetyl or 3-phenylpropionyl, that is unsubstituted or mono- or poly-substituted in the phenyl radical by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, for example methoxy, piperidinomethyl, piperazin-l-ylmethyl, 4-lower alkyl-piperazin-1-ylmethyl, such as 4-methyl- or 4-ethyl-piperazin-1-ylmethyl, morpholinomethyl, thiomorpholinomethyl, cyano and/or by nitro, for example 4-chloro-methyl-, 4-bromomethyl-, 4-fluoro-, 4-chloro-, 4-methoxy-, 4-morpholinoraethyl-, 4-thiomorpholinomethyl-, 4-cyano- or 4-nitro-benzoyl, 4-methylphenylacetyl, 4-methoxy-phenylacetyl or 3-(p-hydroxyphenyl)-propionyl; or is the residue, bonded via its a-carbonyl group, of an aliphatic amino acid selected from alanine, valine, norvaline, leucine, 3-aminopropionic acid, 2-aminobutyric acid and isoleucine or of an amino acid selected from glycine, asparagine, glutamine, methionine, lysine and phenylalanine, or of an amino acid selected from 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, 5-aminopentanoic acid, 3-aminohexanoic acid, 4-aminohexanoic acid and 5-aminohexanoic acid, it being possible for each of the mentioned amino acids to be in the D-, L- or (DJL)-form, preferably in the L-form (except where there are no asymmetric carbon atoms, for example in the case of glycine); an a-amino group, if present, is unsubstituted or is mono- or di-N-alkylated by lower alkyl, such as methyl, n-propyl or n-butyl, by phenyl-lower alkyl, such as benzyl, and/or by 2-, 3- or 4-pyridyl-lower alkyl, such as 2-, 3- or 4-pyridylmethyl, and/or is N-acylated by lower alkoxycarbonyl, such as tert-butoxycarbonyl, or by benzyloxycarbonyl, for example as in alanyl, N-lower alkylalanyl, such as N-methylalanyl, phenylalanyl, aminoacetyl (glycyl), N-lower alkylaminoacetyl or N,N-di-lower alkylaminoacetyl, such as N-methylaminoacetyl, N,N-dimethylaminoacetyl or N-methyl-N-(n-butyl)aminoacetyl, N-lower alkyl-N-phenyl-lower alkylaminoacetyl, such as N-methyl-N-benzylaminoacetyl, N-lower alkyl-N-pyridyl-lower alkylaminoacetyl, for example N-methyl-N-[(2-, 3- or 4-)pyridylmethyl]-aminoacetyl, such as N-methyl-N-(3-pyridylmethyl)aminoacetyl, N-phenyl-lower alkoxycarbonyl-N-lower alkylaminoacetyl, such as N-benzyloxycarbonyl-N-methylaminoacetyl, 2-aminobutyryl, valyl, norvalyl, leucyl, isoleucyl, methionyl, lysyl, glutamyl or asparagyl, wherein the amino acid residues (with the exception of glycine) are preferably in the (L)-form, and pharmaceutical^ acceptable salts thereof. Greater preference may also be given to compounds of formula I and salts thereof wherein Rj is aminocarbonyl, mono- or di-lower alkylaminocarbonyl, such as N-methyl-, N-ethyl-, N,N-dimethyl- or N,N-diethyl-aminocarbonyl, preferably mono- ^0 fJQ -40- lower alkylaminocarbonyl, or phenyl-lower alkylaminocarbonyl wherein phenyl is unsubstituted or substituted by the radicals mentioned in the definition of aryl, for example by lower alkyl, for example methyl, halo-lower alkyl, such as chloro- or bromo-methyl or trifluoromethyl, halogen, for example fluorine or chlorine, hydroxy, lower alkoxy, such as methoxy, carboxy and/or by cyano, preferably by up to three of those substituents selected independently of one another, especially by one of those substituents, for example in the p-position, such as in N-benzyl-, N-(4-fluorobenzyl)-, N-(4-chloroben-zyl)-, N-(4-trifluoromethylbenzyl)- or N-(4-cyanobenzyl)-aminocarbonyL Preference is given especially to compounds of formula I wherein Ri is octanoyl, decanoyl, dodecanoyl, palmitoyl, lower alkanoyl, such as acetyl, propionyl, butyryl, methylpropionyl, n-pentanoyl, pivaloyl, hexanoyl or heptanoyl, lower alkoxy-lower alkanoyl, such as methoxyacetyl, 3-methoxypropionyl or 4-butoxyacetyl, lower alkoxy-lower alkoxy-lower alkanoyl, such as 2-(2-methoxyethoxy)ethoxyacetyl, lower alkoxy-lower alkoxy-lower alkanoyl, such as 2-(2-(2-methoxyethoxy)ethoxy)acetyl, phenoxy-lower alkanoyl, such as phenoxyacetyl, phenyl-lower alkoxy-lower alkanoyl, such as benzyloxyacetyl, 2-halo-lower alkanoyl, such as 2-chloroacetyl, amino-, lower alkylamino- or di-lower alkylamino-lower alkoxy-2-lower alkanoyl, such as dimethylamino-lower alkoxyacetyl, amino-, lower alkylamino- or di-lower alkylamino-lower alkoxy-lower alkoxy-2-lower alkanoyl, such as dimethylamino-(2-lower alkoxyethoxy)acetyl, 2-lower alkoxy-2-phenylacetyl, such as (R)- or (S)-2-metlioxy-2-phenylacetyl, furyl-carbonyl, for example furan-2-ylcarbonyl, pyridyl-lower alkanoyl, for example pyridyl-carbonyl, such as 2-, 3- or 4-pyridylcarbonyl, pyridylacetyl, such as 2-pyridylacetyl, or pyridylpropionyl, such as 3-(pyridin-2-yl)propionyl, quinolylcarbonyl, such as quinolin-2-ylcarbonyl, isoquinolylcarbonyl, such as isoquinolin-3-ylcaxbonyl, pyrrolidinyl-2-carbonyl, especially L- or D-prolyl, imidazolyl-lower alkanoyl, such as 4-imidazolyl-carbonyl, imidazolylacetyl, for example 4-imidazolylacetyl, or imidazolylpropionyl, such as 3-(4-imidazolyl)propionyl, pyrazolyl-lower alkanoyl, such as 1-pyrazolylcarbonyl, phenyl-lower alkanoyl, for example benzoyl, phenylacetyl or 3-phenylpropionyl, 4-chloro-methylbenzoyl, 4-morpholinomethylbenzoyl, 4-thiomorpholinomethylbenzoyl, amino-acetyl, N-lower alkylaminoacetyl or N,N-di-lower alkylaminoacetyl, such as N-methyl-aminoacetyl, N,N-dimethylaminoacetyl or N-methyl-N-(n-butyl)aminoacetyl, N-lower alkyl-N-phenyl-lower alkylaminoacetyl, such as N-methyl-N-benzylaminoacetyl, N-lower alkyl-N-benzyloxycarbonylaminoacetyl, such as N-methyl-N-benzyloxyaminoacetyl, N-imidazolyl-lower alkyl-N-lower alkylaminoacetyl, such as N-(imidazol-4-ylmethyl)-N-methylaminoacetyl, N-lower alkyl-N-pyridyl-lower alkylaminoacetyl, for example -41- N-methyl-N-[(2-, 3- or 4-)pyridylmethyl]-aminoacetyl, such as N-methyl-N-(2- or 3-pyri-dylmethyl)aminoacetyl, or 4-(NJSf-dimethylamino)butyryl, and to pharmaceutical^ acceptable salts thereof. Preference is given more especially to compounds of formula I wherein Ri is lower alkanoyl, such as acetyl, propionyl, butyryl, pivaloyl, hexanoyl orheptanoyl, furylcar-bonyl, for example furan-2-ylcarbonyl, pyridylcarbonyl, for example 2-, 3- or 4-pyridyl-carbonyl, phenyl-lower alkanoyl, for example benzoyl, phenylacetyl or 3-phenylpropionyl, 4-morpholinomethylbenzoyl, 4-thiomorpholinomethylbenzoyl, aminoacetyl, N-lower alkylaminoacetyl, N,N-di-lower alkylaminoacetyl, such as N-methylaminoacetyl, N ,N-dimethylaminoacetyl, N-methyl-N-(n-butyl)aminoacetyl, N-lower alkyl-N-phenyl-lower alkylaminoacetyl, such as N-methyl-N-benzylaminoacetyl, or N-lower alkyl-N-pyridyl-lower alkylaminoacetyl, for example N-methyl-N- [(2-, 3- or 4-)pyridyl-methyl]-aminoacetyl, such as N-methyl-N-(3-pyridylmethyl)aminoacetyl, and to pharma-ceutically acceptable salts thereof. Very special preference is given to compounds of formula I wherein Rj is lower alkanoyl, such as acetyl, lower alkoxy-lower alkanoyl, such as methoxyacetyl, pyridylcarbonyl, such as pyridin-2-ylcarbonyl, or furylcarbonyl, such as furan-2-ylcarbonyl, and to pharmaceut-ically acceptable salts thereof. Preference is given more especially to compounds of formula I wherein Rj is lower alkanoyl, such as acetyl, or furylcarbonyl, such as furan-2-ylcarbonyl, and to pharmaceutical^ acceptable salts thereof. Preference is given very especially also to compounds of formula I wherein Rx is lower alkoxy-lower alkanoyl, such as methoxyacetyl, or pyridylcarbonyl, such as pyridin-2-yl-carbonyl, and to pharmaceutically acceptable salts thereof. Preference is given most especially to compounds of formula I wherein Rj^ is lower alkanoyl, especially acetyl, and to pharmaceutically acceptable salts thereof. Special preference is given to the compounds of formula I mentioned in the Examples and to the pharmaceutically acceptable salts thereof. The compounds of the formula I and salts of such compounds having at least one V \J -42- salt-forming group are obtained in accordance with processes known per se, for example: a) by reacting a compound of formula II, as defined above, with a carboxylic acid of formula in wherein Rj is as defined, or with a reactive derivative thereof, free functional groups in the starting materials of formulae II and m that are not intended to participate in the reaction being if necessary in protected form, and removing any protecting groups present, or b) by amidating an amino compound of formula IV wherein Rj is as defined, or a reactive derivative thereof, with a carboxylic acid of formula V RrOH m O II (V) or with a reactive acid derivative thereof, free functional groups in the starting materials of formulae IV and V that are not intended to participate in the reaction being if necessary in -43- protected form, and removing any protecting groups present, or c) by amidating an amino compound of formula VI wherein Rx is as defined, or a reactive derivative thereof, with a carboxylic acid of formula VII or with a reactive acid derivative thereof, free functional groups in the starting materials of formulae VI and VII that are not intended to participate in the reaction being if necessary in protected form, and removing any protecting groups present, and, if desired, converting a compound of formula I obtainable in accordance with the above process having at least one salt-forming group into its salt and/or converting an -44- obtainable salt into the free compound or into a different salt and/or separating any isomeric mixtures of compounds of formula I that are obtainable and/or converting a compound of formula I according to the invention into a different compound of formula I according to the invention. The processes defined above are described in detail below: Process al Preparation of an acvlated compound The preparation of an ester is effected, for example, in a manner known per se using an acid of formula III wherein Ri is as defined with the exception of aminocarbonyl and the radical of an N-substituted carbamic acid, or using a reactive derivative thereof. A suitable reactive derivative is, for example, a compound of formula ma Ri-Zi (Ma), wherein Rx is as last defined and Zj is especially reactively activated hydroxy. The free carboxylic acid of formula III can be activated, for example, by strong acids, such as a hydrohalic, sulfuric, sulfonic or carboxylic acid, or by acidic ion exchangers, for example hydrochloric, hydrobromic or hydriodic acid, sulfuric acid, an unsubstituted or substituted, for example halo-substituted, alkanecarboxylic acid, or by an acid of formula m, preferably using an excess of the acid of formula HI, if necessary with the binding of resulting water of reaction by water-binding agents, with removal of the water of reaction by azeotropic distillation or with extractive esterification, by acid anhydrides, especially inorganic acid anhydrides, such as carboxylic acid anhydrides, such as lower alkanecarboxylic acid anhydrides (with the exception of formic acid anhydride), for example acetic anhydride, or by suitable activating or coupling reagents of the type listed below, especially also in situ. Rj-Zj may also be a carboxylic acid azide (obtainable, for example, by reaction of a corresponding acid ester via the corresponding hydrazide and treatment thereof with nitrous acid); a carboxylic acid halide, especially an acid chloride or bromide, obtainable, for example, by reaction with organic acid halides, especially with oxalyl dihalides, such as oxalyl dichloride, or especially with inorganic acid halides, for example with acid halides of phosphorus or sulfur, such as phosphorus trichloride, phosphorus tribromide, phosphorus pentachloride, phosphorus pentabromide, phosphorus oxychloride, phosphorus oxybromide, thionyl chloride or thionyl bromide, or especially under mild conditions with tetra-lower alkyl-a-halo-enamines, such as tetramethyl-a-halo-enamines, especially l-chloro-N,N,2-trimethyl- 1-propenamine (preferably by -45- reaction in inert solvents, especially chlorinated hydrocarbons, such as methylene chloride or chloroform, or ethers, such as diethyl ether, dioxane or tetrahydrofuran, at preferred temperatures of from -78 to 50°C, especially from -60 to 30°C, for example from -10°C to room temperature (cf. Devos, A., et al., J. C. S. Chem. Commun. 1979,1180-1181, and Haveaux, B., et aL, Org. Synth. 59,26 (1980)), it being possible for the resulting acid halide, for example the acid chloride of formula ma wherein Zi is chlorine, also to be further processed in situ, for example by reaction with the compound of formula II in the presence of tertiary nitrogen bases, such as pyridine and/or 4-dimethylaminopyridine (DMAP, which is preferably added in catalytic amounts), at preferred temperatures of from -20 to 50°C, especially from 0°C to room temperature); an activated ester wherein Zj is especially cyanomethoxy, nitrophenoxy, such as 4-nitrophenoxy or 2,4-dinitrophenoxy, or poly-halophenoxy, such as pentachlorophenoxy; or a symmetrical or, preferably, asymmetrical acid anhydride which can be obtained, for example, by the reaction of a salt, for example an alkali metal salt, such as the sodium or potassium salt, of an acid of formula in or its co-reactant, preferably a lower alkanecarboxylic acid, such as acetic acid, with a corresponding complementary acid halide, especially, in the case of the reaction of a salt of a carboxylic acid of formula IH, a carboxylic acid halide, for example chloride, such as acetyl chloride, and, in the case of the reaction of a carboxylic acid halide of formula ma wherein Zt is halogen, for example chlorine or bromine, with a salt of a lower alkanecarboxylic acid, especially sodium or potassium acetate. There may be used as activating and coupling reagents for activating carboxylic acids of formula HI in situ especially carbodiimides, for example NJN'-di-C1-C4alkyl- or N,N'-di-C5-C7cyclo-alkyl-carbodiimide, such as diisopropylcarbodiimide or N,N' -dicyclohexylcarbodiimide, advantageously with the addition of an activating catalyst, such as N-hydroxysuccinimide or unsubstituted or substituted, for example halo-, Cj-C^alkyl- or Cj-C^alkoxy-substituted, N-hydroxy-benzotriazole or N-hydroxy-5-norbomene-2,3-dicarboxamide, C1-C4alkylhalo-formate, for example isobutyl chloroformate, suitable carbonyl compounds, for example N,N-carbonyldiimidazole, suitable 1,2-oxazolium compounds, for example 2-ethyl-5-phenyl-l,2-oxazolium 3'-sulfonate or 2-tert-butyl-5-methyl-isoxazolium perchlorate, suitable acylamino compounds, for example 2-ethoxy-l-ethoxycarbonyl-l,2-dihydro-quinoline, or suitable phosphoryl cyanamides or azides, for example diethylphosphoryl cyanamide or diphenylphosphoryl azide, also triphenylphosphinc disulfide or l-Ci-C4alkyl-2-halopyridinium halides, for example l-methyl-2-chloropyridinium iodide. Zj is preferably halogen, such as chlorine or bromine, and acyloxy, for example lower alkanoyloxy, such as acetoxy. -46- For the specific case of the introduction of an acyl radical of a semiester of carbonic acid linked via its carbonyl group to the bonding oxygen atom there are suitable especially the compounds of formula TTTa wherein Zj is halogen, such as chlorine, which can be prepared, for example, by reaction of the complementary alcohols, for example unsubstituted or substituted alkyl alcohols, aryl-lower alkyl alcohols or heterocyclyl-lower alkyl alcohols wherein the radicals are as defined in the definition of unsubstituted or substituted alkoxycarbonyl, aryl-lower alkoxycarbonyl or heterocyclyl-lower alkoxycarbonyl R5, with phosgene or with analogues thereof that contain other halogen atoms, especially bromine, instead of chlorine, preferably in the presence of tertiary nitrogen bases, such as pyridine or triethylamine, and in inert solvents, for example chlorinated hydrocarbons, such as methylene chloride or chloroform, ethers, such as diethyl ether, tetrahydrofuran or dioxane, or carboxylic acid amides, such as dimethyl-formamide. Also suitable are corresponding N-caibonyl azolides of formula IQa (Z1 = an N-containing heterocycle, such as 1-imidazolido) which are obtained, for example, by reaction with the corresponding N,N'-carbonyl diazolides, such as N,N-carbonyl diimidazole, under conditions such as those just described for phosgene and analogues with other halogen atoms. The reaction of compounds of formula H with corresponding compounds of formula ma then likewise takes place under those conditions (cf. Staab, H. A., Angew. Chemie 74,407 (1962)). For the specific case of the introduction of aminocarbonyl Rx or of an N-substituted carbamic acid radical as acyl group Rj there is suitable as activated acid derivative especially the corresponding isocyanate of formula nib Q-N=C=0 (nib) wherein Q is a protecting group, for example trihaloacetyl, such as trifluoro- or trichloro-acetyl, or one of the unsubstituted or substituted lower alkyl radicals or aryl radicals mentioned above in the definition of an aminocarbonyl radical R} wherein the amino group carries 1 or 2 substituents, it being possible, when Q is an amino-protecting group, to obtain after the reaction with the compound of formula n the corresponding compound of formula I wherein R1 is free aminocarbonyl by removal of a protecting group Q as described below for the freeing of amino protected by acyl, especially by acid hydrolysis, or, when Q is one of the mentioned substituted or unsubstituted lower alkyl or aryl radicals, a corresponding compound of formula I having aminocarbonyl mono-substituted -47- at the nitrogen atom. Both aminocarbonyl and N-mono-substituted aminocarbonyl can be converted into N-disubstituted aminocarbonyl by alkylation, as described below in the "Additional Process Steps". The reactions can be carried out under reaction conditions known per se, at customary temperatures, in the presence or, especially when lower alkanoyl anhydrides are used to activate the carboxylic acid of formula m, in the absence of inert solvents or diluents, for example in acid amides, for example carboxylic acid amides, such as dimethylformamide, dimethylacetamide or l,3-dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidinone (DMPU), or amides of inorganic acids, such as hexamethylphosphoric acid triamide, ethers, for example cyclic ethers, such as tetrahydrofuran or dioxane, or acyclic ethers, such as diethyl ether or ethylene glycol dimethyl ether, halogenated hydrocarbons, such as halo-lower alkanes, for example methylene chloride or chloroform, ketones, such as acetone, nitriles, such as acetonitrile, acid anhydrides, such as acetic anhydride, esters, such as ethyl acetate, bisalkane sulfines, such as dimethyl sulfoxide, nitrogen hetero-cycles, such as pyridine, or mixtures of those solvents, especially in anhydrous solvents or solvent mixtures, it being possible to select for the above-mentioned reactions the particular solvents that are suitable in each case, there being used, as appropriate and expedient, salts of the compounds used, especially metal salts of carboxylic acids that are used, such as the alkali metal or alkaline earth metal salts, for example sodium or potassium salts, in the absence or the presence of catalysts, condensation agents or neutralising agents and, depending on the nature of the reaction and/or the reactants, under atmospheric pressure or in a closed vessel, under normal pressure or under elevated pressure, for example at the pressure produced in the reaction mixture under the reaction conditions in a closed tube, and/or in an inert atmosphere, for example under an argon or nitrogen atomsphere. Preference is given to reaction conditions that are analogous to those mentioned in the Examples. Furthermore, the acylating agent, for example a carboxylic acid halide or a carboxylic acid anhydride, can itself serve as solvent The course of the reaction is advantageously monitored using customary methods of analysis, especially using thin-layer chromatography. Unless otherwise indicated, the reaction according to the invention is preferably carried out under mild conditions, especially at temperatures of from 0°C to 60°C, for example at room temperature or at slightly elevated temperatures up to about 45°C, for example approximately at room temperature. If the reaction is carried out with a compound of formula Ri-Zj wherein is halogen, or with an activated derivative of a compound of 9 ^ n c <j> \j i) ! -48- formula II, such as the corresponding chlonocarbonic acid ester, then, for the preparation of a compound of formula I wherein Rj is aminocarbonyl or the radical of an N-substituted carbamic acid, the reaction is advantageously carded one in the presence of an acid-binding agent, such as a non-acylatable base, especially a tertiary nitrogen base, such as N-methylmorpholine, 4-dimethylaminqpyridine, triethylamine or ethyl diisopropylamine. Both in the case of the reaction with a carboxylic acid halide of formula Hla wherein Zj is halogen, such as chlorine or bromine, and in the case of the reaction with an anhydride, especially a symmetrical anhydride (Z1 = O-Rj), there is used especially an excess of the corresponding compound of formula ma (halide and R^O-R^ respectively), for example a more than 1.05-fold excess. Reaction conditions that axe specifically mentioned in each case are preferred. The protecting groups for functional groups in starting materials the reaction of which is to be avoided, especially carboxy, amino, hydroxy and/or mercapto groups, include especially those protecting groups (conventional protecting groups) which are customarily used in the synthesis of peptide compounds, and also in the synthesis of cephalosporins and penicillins as well as nucleic acid derivatives and sugars. Those protecting groups may already be present in the precursors and are intended to protect the functional groups in question against undesired secondary reactions, such as acylation, etherification, esterification, oxidation, solvolysis, In certain cases the protecting groups can additionally cause the reactions to proceed selectively, for example stereoselectively. It is a characteristic of protecting groups that they tan be removed easily, i.e. without undesired secondary reactions talcing place, for example by solvolysis, reduction, photolysis, and also enzymatically, for exaffiple also under physiological conditions. Only those radicals that are not present in the end products are referred to as protecting groups. The protection of functional groups by such protecting groups, the protecting groups themselves and the reactions for their removal are described, for example, in standard works such as J. F. W. McOmie, "Protective Groups in Organic Chemistry", Plenum Press, London and New York 1973, in Th. W. Greene, "Protective Groups in Organic Synthesis", Wiley, New York 1981, in "The Peptides", Volume 3 (E. Gross and J. Meienhofer, eds.), Academic Press, London and New York 1981, in "Methoden der organischen Chemie", Houben-Weyl, 4th edition, Volume 15/1, Georg Thieme Verlag, Stuttgart 1974, in H.-D. Jakubke and H. Jescheit, "Aminos&uren, Peptide, Proteine" ("Amino acids, peptides, proteins"), Verlag Chemie, Weinheim, Deerfield Beach and Basle 1982, and in Jochen Lehmann, "Chemie der Kohlenhydrate: Monosaccharide und Derivate" ("The Chemistry 2 5 0 0 1 -49- of Carbohydrates: monosaccharides and derivatives"), Georg Thieme Verlag, Stuttgart 1974. A carboxy group is protected, for example, in the form of an ester group which can be cleaved selectively under mild conditions. A carboxy group protected in esterified form is esterified especially by a lower alkyl group that is preferably branched in the 1-position of the lower alkyl group or substituted in the 1- or 2-position of the lower alkyl group by suitable substituents. A protected carboxy group esterified by a lower alkyl group is, for example, methoxy-carbonyl or ethoxycarbonyl. A protected carboxy group esterified by a lower alkyl group that is branched in 'he 1-posidon of the lower alkyl group is, for example, tert-lower alkoxycarbonyl, for example tert-butoxycarbonyl. A protected carboxy group esterified by a lower alkyl group that is substituted in the 1- or 2-position of the lower alkyl group by suitable substituents is, for example, arylmethoxy-carbonyl having one or two aryl radicals, wherein aryl is phenyl that is unsubstituted or mono-, di- or tri-substituted, for example, by lower alkyl, for example tert-lower alkyl, such as tert-butyl, lower alkoxy, for example methoxy, hydroxy, halogen, for example chlorine, and/or by nitro, for example benzyloxycarbonyl, benzyloxycarbonyl substituted by the mentioned substituents, for example 4-nitrobenzyloxycarbonyl or 4-methoxy-benzyloxycarbonyl, diphenylmethoxycarbonyl or diphenylmethoxycarbonyl substituted by the mentioned substituents, for example di(4-methoxyphenyl)methoxycarbonyl, and also carboxy esterified by a lower alkyl group, the lower alkyl group being substituted in the 1-or 2-position by suitable substituents, such as 1-lower alkoxy-lower alkoxycarbonyl, for example methoxymethoxycarbonyl, 1 -methoxychoxycarbonyl or 1-ethoxyethoxy-carbonyl, 1-lower alkylthio-lower alkoxycarbonyl, for example 1 -methyl thiomethoxy-carbonyl or 1-ethylthioethoxycarbonyl, aroylmethoxycarbonyl wherein the aroyl group is benzoyl that is unsubstituted or substituted, for example, by halogen, such as bromine, for example phenacyloxycarbonyl, 2-halo-lower alkoxycarbonyl, for example 2,2,2-trichloro-ethoxycarbonyl, 2-bromoethoxycarbonyl or 2-iodcethoxycarbonyl, as well as 2-(tri-substi-tuted silyl)-lower alkoxycarbonyl wherein t**e substituents are each independently of the others an aliphatic, araliphatic, cycloaliphatic or aromatic hydrocarbon radical that is unsubstituted or substituted, for example, by lower alkyl, lower alkoxy, aryl, halogen -50- and/or by nitro, for example lower alkyl, phenyl-lower alkyl, cycloalkyl or phenyl each of which is unsubstituted or substituted as above, for example 2-tri-lower alkylsilyl-lower alkoxycarbonyl, such as 2-tri-lower alkylsilylethoxycarbonyl, for example 2-trimethyl-silylethoxycarbonyl or 2-(di-n-butyl-methyl-silyl)-ethoxycarbonyl, or 2-triarylsilylethoxy-carbonyl, such as triphenylsilylethoxycarbonyl. A carboxy group is also protected in the form of an organic silyloxycarbonyl group. An organic silyloxycarbonyl group is, for example, a tri-lower alkylsilyloxycarbonyl group, for example trimethylsilyloxycarbonyl. The silicon atom of the silyloxycarbonylgroup can also be substituted by two lower alkyl groups, for example methyl groups, and an amino group or carboxy group of a second molecule of formula L Compounds having such protecting groups can be prepared, for example, using dimethylchlorosilane as silylating agent A carboxy group is also protected in the form of an internal ester by a hydroxy group that is present in the molecule at a suitable distance from the carboxy group, for example in the y-position relative to the carboxy group, i.e. in the form of a lactone, preferably a Y-lactone. A protected carboxy group is preferably tert-lower alkoxycarbonyl, for example tert-butoxycarbonyl, benzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 9-fluorenylmethoxycarbonyl or diphenylmethoxycarbonyl. A protected amino group is protected by an ammo-protecting group, for example in the form of an acylamino, arylmethylamino, etherified mercaptoamino, 2-acyl-lower alk-1-enylamino or silylamino group or in the form of an azido group. In an acylamino group, acyl is, for example, the acyl radical of an organic carboxylic acid having, for example, up to 18 carbon atoms, especially an unsubstituted or substituted, for example halo- or aryl-substituted, lower alkanecarboxylic acid or an unsubstituted or substituted, for example halo-, lower alkoxy- or nitro-substituted, benzoic acid, or, preferably, of a carbonic acid semiester. Such acyl groups are preferably lower alkanoyl, such as formyl, acetyl, propionyl or pivaloyl, halo-lower alkanoyl, for example 2-halo-acetyl, such as 2-chloro-, 2-bromo-, 2-iodo-, 2,2,2-trifluoro- or 2,2,2-trichloro-acetyl, unsubstituted or substituted, for example halo-, lower alkoxy- or nitro-substituted, benzoyl, such as benzoyl, 4-chlorobenzoyl, 4-methoxybenzoyl or 4-nitrobenzoyl, lower -51- alkoxycarbonyl, preferably lower alkoxycarbonyl that is branched in the 1-position of the lower alkyl radical or suitably substituted in the 1- or 2-position, for example tert-lower alkoxycarbonyl, such as tert-butoxycarbonyl, arylmethoxycarbonyl having one, two or three aryl radicals which arc phenyl that is unsubstituted or mono- or poly-substituted, for example, by lower alkyl, especially tert-lower alkyl, such as tert-butyl, lower alkoxy, such as methoxy, hydroxy, halogen, such as chlorine, and/or by nitro, for example benzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, diphenylmethoxycarbonyl, 9-fluorenylmethoxy-carbonyl or di(4-methoxyphenyl)methoxycarbonyl, aroylmethoxycarbonyl wherein the aroyl group is preferably benzoyl that is unsubstituted or substituted, for example, by halogen, such as bromine, for example phenacyloxycarbonyl, 2-halo-lower alkoxycarbonyl, for example 2,2,2-trichloroethoxycarbonyl, 2-bromoethoxycarbonyl or 2-iodo-ethoxycarbonyl, 2-(tri-substituted silyl)-lower alkoxycarbonyl, for example 2-tri-lower alkylsilyl-lower alkoxycarbonyl, such as 2-trimethylsilylethoxycarbonyl or 2-(di-n-butyl-methyl-silyl)-ethoxycaibonyl, or triarylsilyl-lower alkoxycarbonyl, for example 2-triphenylsilylethoxycarbonyl. In an arylmethylamino group, for example a mono-, di- or especially tri-arylmethylamino group, the aryl radicals are especially unsubstituted or substituted phenyl radicals. Such groups are, for example, benzyl-, diphenylmethyl- or especially trityl-amino. In an etherified mercaptoamino group the mercapto group is especially in the form of substituted arylthio or aryl-lower alkylthio, wherein aryl is, for example, phenyl that is unsubstituted or substituted, for example, by lower alkyl, such as methyl or tert-butyl, lower alkoxy, such as methoxy, halogen, such as chlorine, and/or by nitro, for example 4-nitrophenylthio. In a 2-acyl-lower alk-l-enyl radical that can be used as an amino-protecting group, acyl is, for example, the corresponding radical of a lower alkanecarboxylic acid, of a benzoic acid that is unsubstituted or substituted, for example, by lower alkyl, such as methyl or tert-butyl, lower alkoxy, such as methoxy, halogen, such as chlorine, and/or by nitro, or especially of a carbonic acid semiester, such as a carbonic acid lower alkyl semiester. Corresponding protecting groups are especially 1-lower alkanoyl-lower alk-l-en-2-yl, for example 1-lower alkanoylprop-l-en-2-yl, such as l-acetylprop-l-en-2-yJ, or lower alkoxycarbonyl-lower alk-l-en-2-yl, for example lower alkoxycarbonylprop-l-en-2-yl, such as l-ethoxycarbonylprop-l-en-2-yl. -52- A silylamino group is, for example, a tri-lower alkylsilylamino group, for example trimetfaylsilylamino or tert-butyl-dimethylsilylamino. The silicon atom of the silylamino group can also be substituted by only two lower alkyl groups, for example methyl groups, and by the amino group or carboxy group of a second molecule of formula I. Compounds having such protecting groups can be prepared, for example, using the corresponding chlorosilanes, such as dimethylchlorosilane, as silylating agents. An amino group can also be protected by conversion into the protonated form; suitable corresponding anions are especially those of strong inorganic acids, such as sulfuric acid, phosphoric acid or hydrohalic acids, for example the chlorine or bromine anion, or of organic sulfonic acids, such as p-toluenesulfonic acid. Preferred amino-protecting groups are lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, fluorenyl-lower alkoxycarbonyl, 2-lower alkanoyl-lower alk-l-en-2-yl and lower alkoxycarbonyl-lower alk-l-en-2-yl, especially tert-butoxycarbonyl and benzyloxycarbonyl. A hydroxy group can be protected, for example, by an acyl group, for example lower alkanoyl that is unsubstituted or substituted by halogen, such as chlorine, such as acetyl or 2,2-dichloroacetyl, or especially by an acyl radical of a carbonic acid semiester mentioned for protected amino groups. A preferred hydroxy-protecting group is, for example, 2,2,2-trichloroethoxycarbonyl, 4-nitrobenzyloxycarbonyl, diphenylmethoxycarbonyl or triphenylmethoxycarbonyl. A hydroxy group can also be protected by tri-lower alkylsilyl, for example trimethylsilyl, triisopropylsilyl or tert-butyl-dimethylsilyl, a readily removable etherifying group, for example an alkyl group, such as tert-lower alkyl, for example tert-butyl, an oxa- or a thia-aliphatic or -cycloaliphatic, especially 2-oxa- or 2-thia-aliphatic or -cycloaliphatic, hydrocarbon radical, for example 1-lower alkoxy-lower alkyl or 1-lower alkylthio-lower alkyl, such as methoxymethyl, 1-methoxyethyl, 1-ethoxy-ethyl, methylthiomethyl, 1-methylthioethyl or 1-ethylthioethyl, or 2-oxa- or 2-thia-cyclo-alkyl having from 5 to 7 ring atoms, such as 2-tetrahydrofuryl or 2-tetrahydropyranyl, or a corresponding thia analogue, and also by 1-phenyl-lower alkyl, such as benzyl, diphenyl-methyl or trityl, wherein the phenyl radicals can be substituted, for example, by halogen, for example chlorine, lower alkoxy, for example methoxy, and/or by nitro. Two hydroxy groups, especially adjacent hydroxy groups, occurring in a molecule, or a hydroxy group and an amino group that are adjacent to one another, can be protected, for -53- example, by bivalent protecting groups, such as a methylene group that is preferably substituted, for example, by one or two lower alkyl radicals or by oxo, for example unsubstituted or substituted alkylidene, for example lower alkylidene, such as isopropyl-idene, cycloalkylidene, such as cyclohexylidene, a carbonyl group or benzylidene. A hydroxy group in a position adjacent to a carboxy group can be protected by the formation of an internal ester (lactone), especially a y-lactone. Preference is given to a protected hydroxy group protected by tri-lower alkylsilyl or in the form of a lactone, especially by tert-butyl-dimethylsilyl. A mercapto group, for example in cysteine, can be protected especially by S-alkylation with unsubstituted or substituted alkyl radicals, by silylation, by thioacetal formation, by S-acylation or by the formation of asymmetric disulfide groupings. Preferred mercapto-protecting groups are, for example, benzyl that is unsubstituted or substituted in the phenyl radical, for example by methoxy or by nitro, such as 4-methoxybenzyl, diphenylmethyl that is unsubstituted or substituted in the phenyl radical, for example by methoxy, such as di(4-methoxyphenyl)methyl, triphenylmethyl, pyridyldiphenylmethyl, trimethylsilyl, benzylthiomethyl, tetrahydropyranyl, acylaminomethyl, such as acetamidomethyl, iso-butyrylacetamidomethyl or 2-chloroacetamidomethyl, benzoyl, benzyloxycarbonyl or alkyl-, especially lower alkyl-aminocarbonyl, such as ethylaminocarbonyl, and also lower alkylthio, such as S-ethylthio or S-tert-butylthio, or S-sulfo. The removal of protecting groups that are not constituents of the desired end product of formula I, for example the carboxy-, amino-, hydroxy- and/or mercapto-protecting groups, is effected in a manner known per se, for example by means of solvolysis, especially hydrolysis, alcoholysis or acidolysis, or by means of reduction, especially hydrogenolysis or by means of other reducing agents, as well as by photolysis, as desired stepwise or simultaneously, it being possible also to use enzymatic methods. The removal of the protecting groups is described, for example, in the standard works mentioned above in the section relating to protecting groups. For example, protected carboxy, for example tert-lower alkoxycarbonyl, lower alkoxycarbonyl substituted in the 2-position by a trisubstituted silyl group or in the 1-position by lower alkoxy or by lower alkylthio, or unsubstituted or substituted diphenylmethoxycarbonyl can be converted into free caiboxy by treatment with a suitable acid, such as * w U !! / -54- formic acid, hydrogen chloride or trifluoroacetic acid, where appropriate with the addition of a nucleophilic compound, such as phenol or anisole. Unsubstituted or substituted benzyloxycarbonyl can be freed, for example, by means of hydrogenolysis, i.e. by treatment with hydrogen in the presence of a metal hydrogenation catalyst, such as a palladium catalyst In addition, suitably substituted benzyloxycarbonyl, such as 4-nitrobenzyloxycarbonyl, can be converted into free carboxy also by reduction, for example by treatment with an alkali metal dithionite, such as sodium dithionite, or with a reducing metal, for example zinc, or a reducing metal salt, such as a chromium(II) salt, for example chromium(II) chloride, customarily in the presence of a hydrogen-yielding agent that, together with the metal, is capable of producing nascent hydrogen, such as an acid, especially a suitable carboxylic acid, such as an unsubstituted or substituted, for example hydroxy-substituted, lower alkanecarboxylic acid, for example acetic acid, formic acid, glycolic acid, diphenylglycolic acid, lactic acid, mandelic acid, 4-chloromandelic acid or tartaric acid, or in the presence of an alcohol or thiol, water preferably being added. By treatment with a reducing metal or metal salt, as described above, 2-halo-lower alkoxycarbonyl (where appropriate after conversion of a 2-bromo-lower alkoxycarbonyl group into a corresponding 2-iodo-lower alkoxycarbonyl group) or aroylmethoxycarbonyl can also be converted into free carboxy. Aroylmethoxycarbonyl can be cleaved also by treatment with a nucleophilic, preferably salt-foiming, reagent, such as sodium thio-phenolate or sodium iodide. 2-(tri-substituted silyl)-lower alkoxycarbonyl, such as 2-tri-lower alkylsilyl-lower alkoxycarbonyl, can be converted into free carboxy also by treatment with a salt of hydrofluoric acid that yields the fluoride anion, such as an alkali metal fluoride, for example sodium or potassium fluoride, where appropriate in the presence of a macrocyclic polyether ("crown ether"), or with a fluoride of an organic quaternary base, such as tetra-lower alkylammonium fluoride or tri-lower alkylaryl-lower alkylammonium fluoride, for example tetraethylammonium fluoride or tetrabutyl-ammonium fluoride, in the presence of an aprotic, polar solvent, such as dimethyl sulfoxide or N,N-dimethylacetamide. Carboxy protected in the form of organic silyloxycarbonyl, such as tri-lower alkylsilyloxycarbonyl, for example trimethylsilyloxycarbonyl, can be freed in customary manner by solvolysis, for example by treatment with water, an alcohol or an acid, or, furthermore, a fluoride, as described above. Esterified carboxy can also be freed enzymatically, for example by means of esterases or suitable peptidases, for example esterified arginine or lysine, such as lysine methyl ester, using trypsin. Carboxy protected in the form of an internal ester, such as Y-lactone, can be freed by hydrolysis in the presence of a hydroxide-containing base, such as an alkaline earth metal hydroxide or especially an alkali metal hydroxide, for example NaOH, KOH or LiOH, especially LiOH, the correspondingly protected hydroxy group being freed at the same time. A protected amino group is freed in a manner known per se and, according to the nature of the protecting groups, in various ways, preferably by solvolysis or reduction. Lower alkoxycarbonylamino, such as tert-butoxycarbonylamino, can be cleaved in the presence of acids, for example mineral acids, for example a hydrogen halide, such as hydrogen chloride or hydrogen bromide, especially hydrogen bromide, or sulfuric or phosphoric acids, preferably hydrogen chloride, in polar solvents, such as water or a carboxylic acid, such as acetic acid, or ethers, preferably cyclic ethers, such as dioxane, and 2-halo-lower alkoxycarbonylamino (where appropriate after conversion of a 2-bromo-lower alkoxycarbonylamino group into a 2-iodo-lower alkoxycarbonylamino group), aroylmethoxy-carbonylamino or 4-nitrobenzyloxycarbonylamino can be cleaved, for example, by treatment with a suitable reducing agent, such as zinc in the presence of a suitable carboxylic acid, such as aqueous acetic acid. Aroylmethoxycarbonylamino can be cleaved also by treatment with a nucleophilic, preferably salt-forming, reagent, such as sodium thiophenolate, and 4-nitrobenzyloxycarbonylamino also by treatment with an alkali metal dithionite, for example sodium dithionite. Unsubstituted or substituted diphenylmethoxy-carbonylamino, tert-lower alkoxycarbonylamino or 2-(tri-substituted silyl)-lower alkoxycarbonylamino, such as 2-tri-lower alkylsilyl-lower alkoxycarbonylamino, can be freed by treatment with a suitable acid, for example formic acid or trifluoroacetic acid; unsubstituted or substituted benzyloxycarbonylamino can be freed, for example, by means of hydrogenolysis, i.e. by treatment with hydrogen in the presence of a suitable hydrogenation catalyst, such as a palladium catalyst, preferably in polar solvents, such as di-lower alkyl-lower alkanoylamides, for example dimethylformamide, ethers, such as cyclic ethers, for example dioxane, or alcohols, such as methanol, ethanol or propanol, methanol being especially preferred; unsubstituted or substituted triarylmethylamino or formylamino can be freed, for example, by treatment with an acid, such as a mineral acid, for example hydrochloric acid, or an organic acid, for example formic, acetic or trifluoroacetic acid, where appropriate in the presence of water; and an amino group protected in the form of silylamino can be freed, for example, by means of hydrolysis or alcoholysis. An amino group protected by 2-haloacetyl, for example 2-chloroacetyl, can be freed by treatment with thiourea in the presence of a base, or with a thiolate salt, such as an alkali metal thiolate of thiourea, and subsequent solvolysis, such as alcoholysis or hydrolysis, of the resulting substitution product An amino group protected by 2-(tri-substituted silyl)-lower alkoxycarbonyl, such as 2-tri-lower alkylsilyl-lower alkoxycarbonyl, can be converted into the free amino group also by treatment with a salt of hydrofluoric acid that -56- yields fluoride anions, as indicated above in connection with the freeing of a correspondingly protected carboxy group. Likewise, silyl, such as trimethylsilyl, bonded directly to a hetero atom, such as nitrogen, can be removed using fluoride ions. Amino protected in the form of an azido group is converted into free amino, for example, by reduction, for example by catalytic hydrogenation with hydrogen in the presence of a hydrogenation catalyst, such as platinum oxide, palladium or Raney nickel, by reduction using mercapto compounds, such as dithiothreitol or mercaptoethanol, or by treatment with zinc in the presence of an acid, such as acetic acid. The catalytic hydrogenation is preferably carried out in an inert solvent, such as a halogeoated hydrocarbon, for example methylene chloride, or in water or in a mixture of water and an organic solvent, such as an alcohol or dioxane, at approximately from 20°C to 25°C, or with cooling or heating. A hydroxy or mercapto group protected by a suitable acyl group, by a tri-lower alkylsilyl group or by unsubstituted or substituted 1-phenyl-lower alkyl is freed analogously to a correspondingly protected amino group. A hydroxy or mercapto group protected by 2,2-dichloroacetyl is freed, for example, by basic hydrolysis, and a hydroxy or mercapto group protected by tert-lower alkyl or by a 2-oxa- or 2-thia-aliphatic or 2-oxa- or 2-thia-cycloaliphatic hydrocarbon radical is freed by acidolysis, for example by treatment with a mineral acid or a strong carboxylic acid, for example trifluoroacetic acid. Mercapto protected by pyridyldiphenylmethyl can be freed, for example, using mercury(II) salts at pH 2-6 or by zinc/acetic acid or by electrolytic reduction; mercapto protected by acetamidomethyl and isobutyrylamidomethyl can be freed, for example, by reaction with mercury(II) salts at pH 2-6; mercapto protected by 2-chloroacetamidomethyl can be freed, for example, using 1-piperidinothiocarboxamide; and S-ethylthio, S-tert-butylthio and S-sulfo can be freed, for example, by thiolysis with thiophenol, thioglycolic acid, sodium thiophenolate or 1,4-dithiothrcitol. Two hydroxy groups or an adjacent amino and hydroxy group that are protected together by means of a bivalent protecting group, preferably, for example, by a methylene group mono- or di-substituted by lower alkyl, such as lower alkylidene, for example isopropylidene, cycloalkylidene, for example cyclo-hexylidene, or benzylidene, can be freed by acid solvolysis, especially in the presence of a mineral acid or a strong organic acid. A tri-lower alkylsilyl group is likewise removed by acidolysis, for example by a mineral acid, preferably hydrofluoric acid, or a strong carboxylic acid. 2-halo-lower alkoxycarbonyl is removed using the above-mentioned reducing agents, for example a reducing metal, such as zinc, reducing metal salts, such as chromium(II) salts, or by sulfur compounds, for example sodium dithionite or preferably -57- sodium sulfide and carbon disulfide. Esterified hydroxy groups, for example lower alkanoyloxy, such as acetoxy, can be freed also by esterases, and acylated amino, for example, by suitable peptidases. The temperatures for freeing the protected functional groups are preferably from -80 to 100°C, especially from -20 to 50°C, for example from 10 to 35°C, such as in the region of room temperature. When several protected functional groups are present, if desired the protecting groups can be so selected that more than one such group can be removed simultaneously, for example by acidolysis, such as by treatment with trifluoroacetic acid, or with hydrogen and a hydrogenation catalyst, such as a palladium-on-carbon catalyst Conversely, the groups can also be so selected that they cannot all be removed simultaneously, but rather can be removed in a desired sequence, the corresponding intermediates being obtained. The starting compound of formula II is obtainable ftom 2-[3(S)-amino-2(R)-hydroxy-4-phenylbutyl]-N-tert-butyl-decahydro-(4aS,8aS)-isoquinoline-3(S)-carboxamide (which can be prepared analogously to EP 0 432 695, Example 33) which can also be obtained, for example, by reacting a compound of formula VIII wherein Pj is an amino-protecting group, as defined above under Process a), especially tert-butoxycarbonyl or benzyloxycarbonyl, that can be prepared in accordance with Evans et aL, J. Org. Chem. 50,4615-4625 (1985), with N-tert-butyldecahydro-(4aS,8aS)-iso-quinoline-3(S)-carboxamide (prepared in accordance with EP 0 432 694), for example in a polar solvent, such as an alcohol, for example methanol or ethanol, at elevated temperature, for example from 40 to 90°C, such as reflux temperature, there being obtained a compound of formula IX -58- wherein Pi is as last defined, and subsequently removing the amino-pro tec ting group Pi, for example in the case where Pi is tert-butoxycarbonyl by removal with an acid, such as a mineral acid, for example a hydrohalic acid, such as hydrochloric acid, or in the presence of a strong organic acid, such as formic acid, in organic solvents, for example an ether, for example a cyclic ether, such as dioxane, or in the case of a liquid organic acid, such as formic acid, without a solvent; or in the case where Pi is benzyloxycarbonyl by hydrogenation in the presence of a catalyst, for example a noble metal catalyst, for example bonded to a carrier, such as carbon, silica gel or aluminium oxide, preferably palladium on active carbon, under normal pressure or elevated pressure, preferably approximately under normal pressure, in a polar solvent, for example an alcohol, such as methanol or ethanol, at from 0 to 50°C, preferably approximately at room temperature; the resulting compound {N-tert-butyl-decahydro-2-[[2(R)-hydioxy-4-phenyl-3(S)-amino]butyl]-(4aS,8aS)-iso-quinoline-3(S)-carboxamide}, or a salt thereof, for example the salt of one of the last-mentioned acids, is amidated either with L-asparagine N-protected by an ammo-pro tcc ting group P2, for example a-(N-benzyloxycarbonyl)-L-asparagine, or with a reactive acid derivative thereof, especially the p-nitrophenyl ester, as described for the amidation under Process b), preferably in the presence of a tertiary nitrogen base, such as triethylamine or N-ethyldiisopropylamine, especially in an acid amide, for example dimethylformamide, at temperatures of from 0 to 50°C, preferably approximately at room temperature, there being obtained the compound of formula X -59- wherein P2 is an amino-pro tec ting group, as defined under Process a), especially benzyloxycarbonyl; the compound of formula X is then converted into the corresponding free amino compound by removal of the protecting groups, in the case where P2 is benzyloxycarbonyl, for example, by hydrogenation in the presence of a catalyst, for example a noble metal catalyst, for example bonded to a carrier, such as carbon, silica gel or aluminium oxide, preferably palladium on active carbon, under normal pressure or elevated pressure, preferably under normal pressure, in a polar solvent, for example an alcohol, such as methanol or ethanol, at from 0 to 50°C, preferably approximately at room temperature, which amino compound is then amidated by reaction with quinoline-2-carboxylic acid under reaction conditions analogous to those mentioned under Process b), to yield the compound of formula II. Alternatively, the compound of formula n can also be obtained in accordance with the preparation processes mentioned in EP 0 432 695 (published on 19.06.1991). The starting compounds of formula HI are commercially available or known, or they can be prepared in accordance with processes known per se. There may be mentioned by way of example the formation of aryl-lower alkanoyl substituted by heterocyclylmethyl, wherein heterocyclyl is bonded via a ring nitrogen atom, which is preferably effected by reacting an aryl-lower alkanoyl radical substituted by halomethyl, such as chloro- or bromo-methyl, such as chloromethylbenzoyl or bromo-methylbenzoyl, with a corresponding heterocyclic nitrogen base, such as piperidine, piperazine, 1-lower alkylpiperazine, 1-lower alkanoylpiperazine or especially morpholine -60- or thiomorpholine, with nucleophilic substitution of the halogen atom. Amino acid derivatives of formula m wherein the a-amino group is alkylated by a radical selected from phenyl-lower alkyl and heterocyclyl-lower alkyl can be prepared, for example, by reductive amination of the amino acid (protected, if necessary, at further groups that are not intended to participate in the reaction) having a primary or secondary a-amino group, with a phenyl-lower alkyl ketone or aldehyde, such as benzaldehyde, or heterocyclyl-lower alkyl ketone or aldehyde, for example heterocyclyl aldehyde, for example furan aldehyde, such as furan-2-aldehyde, or pyridine aldehyde, such as pyridine-3-aldehyde, or imidazolyl aldehyde, such as imidazol-4-yl aldehyde (if necessary N-protected, for example by trityl which can be removed as described above in the compound of formula HI or the protected end product of formula I, as described above), for example with catalytic hydrogenation, for example in the presence of a heavy metal catalyst, such as Raney nickel, under normal pressure or under pressures of from 1 to 100 bar, preferably at approximately 100 bar, or with reduction by means of complex boron hydrides, such as sodium cyanoboron hydride. The isocyanates of formula nib can be prepared, for example, from the corresponding amine precursors by conversion of the amino group into the isocyanato group, for example by reaction with phosgene with heating, for example under reflux conditions, or by the dropwise addition of the primary, secondary or tertiary amine, in liquid form or dissolved in a solvent, to an excess of phosgene in a suitable solvent (toluene, xylene, ligroin, chlorobenzene, a-chloronaphthalene, etc.) with cooling (for example at from -50 to 0°C), there being formed as intermediate a mixture of carbamoyl chloride and amine hydrochloride which is then phosgenated further at elevated temperature (for example at from 50°C to the reflux temperature) until complete dissolution is obtained, HQ being eliminated. Process b) Amidation (Condensation to form an amide bond) In starting materials of formulae IV and/or V, functional groups that are not intended to participate in the reaction are protected if necessary by protecting groups. The protecting groups and the introduction thereof are as described above under Process a). The carboxylic acid of formula V is either in a form having a free carboxy group or is in the form of a reactive derivative thereof, for example in the form of an activated ester u 0 17 -61- derived from the free carboxy compound, in the form of a reactive anhydride, or in the form of a reactive cyclic amide. The reactive derivatives can also be formed in situ. Activated esters of the compound of formula V having a carboxy group are especially esters unsaturated at the linking carbon atom of the esterifying radical, for example of the vinyl ester type, such as vinyl esters (obtainable, for example, by transesterification of a corresponding ester with vinyl acetate; activated vinyl ester method), carbamoyl esters (obtainable, for example, by treatment of the corresponding acid with an isoxazolium reagent; 1,2-oxazolium or Woodward method), or 1-lower alkoxyvinyl esters (obtainable, for example, by treatment of the corresponding acid with a lower alkoxyacetylene; ethoxy-acetylene method), or esters of the amidino type, such as N,N'-disubstituted amidino esters (obtainable, for example, by treatment of the corresponding acid with a suitable N,N'-disubstituted carbodiimide, for example N,N'-dicyclohexylcarbodiimide; carbo-diimide method), or N,N-disubstituted amidino esters (obtainable, for example, by treatment of the corresponding acid with an N,N-disubstituted cyanamide; cyanamide method), suitable aryl esters, especially phenyl esters substituted by electron-attracting substituents (obtainable, for example, by treatment of the corresponding acid with a suitably substituted phenol, for example 4-nitrophenol, 4-methylsulfonylphenol, 2,4,5-tri-chlorophenol, 2,3,4,5,6-pentachlorophenol or 4-phenyldiazophenol, in the presence of a condensation agent, such as N.N'-dicyclohexylcarbodiimide; activated aryl esters method), cyanomethyl esters (obtainable, for example, by treatment of the corresponding acid with chloroacetonitrile in the presence of a base; cyanomethyl esters method), thio-esters, especially unsubstituted or substituted, for example nitro-substituted, phenylthio esters (obtainable, for example, by treatment of the corresponding acid with unsubstituted or substituted, for example nitro-substituted, thiophenols, inter alia by the anhydride or carbodiimide method; activated thiol esters method), or especially amino or amido esters (obtainable, for example, by treatment of the corresponding acid with an N-hydroxyamino or N-hydroxyamido compound, for example N-hydroxysuccinimide, N-hydroxypiperidine, N-hydroxyphthalimide, N-hydroxy-5-norbomene-2,3-dicarboxylic acid imide, 1-hydroxy-benzotriazole or 3-hydroxy-3,4-dihydro-l,2,3-benzotriazin-4-one, for example by the anhydride or carbodiimide method; activated N-hydroxy esters method). Internal esters, for example y-lactones, can also be used. Anhydrides of the acid may be symmetric or preferably mixed anhydrides of that acid, for example anhydrides with inorganic acids, such as acid halides, especially acid chlorides (obtainable, for example, by treatment of the corresponding acid with thionyl chloride, Q fi. !"■, <■; ^ V' \J , -62- phosphorus pentachlori.de or oxalyl chloride; acid chloride method), azides (obtainable, for example, from a corresponding acid ester via the corresponding hydrazide by treatment thereof with nitrous acid; azide method), anhydrides with carbonic acid semiesters, for example carbonic acid lower alkyl semiesters (obtainable, for example, by treatment of the corresponding acid with chloroformic acid lower alkyl esters or with a 1-lower alkoxy-carbonyl-2-lower alkoxy-1,2-dihydroquinoline; mixed O-alkylcarbonic acid anhydrides method), or anhydrides with dihalogenated, especially dichlorinated, phosphoric acid (obtainable, for example, by treatment of the corresponding acid with phosphorus oxy-chloride; phosphorus oxychloride method), anhydrides with other phosphoric acid derivatives (for example those obtainable with phenyl-N-phenylphosphoramidochloridate or by reaction of alkylphosphoric acid amides in the presence of sulfonic acid anhydrides and/or racemisation-reducing additives, such as N-hydroxybenzotriazole, or in the presence of cyanophosphonic acid diethyl ester) or with phosphorous acid derivatives, or anhydrides with organic acids, such as mixed anhydrides with organic carboxylic acids (obtainable, for example, by treatment of the corresponding acid with an unsubstituted or substituted lower alkane- or phenyl-lower alkane-carboxylic acid halide, for example phenylacetic acid chloride, pivalic acid chloride or trifluoroacetic acid chloride; mixed carboxylic acid anhydrides method) or with organic sulfonic acids (obtainable, for example, by tieatment of a salt, such as an alkali metal salt, of the corresponding acid with a suitable organic sulfonic acid halide, such as lower alkane- or aryl-, for example methane- or p-toluene-sulfonic acid chloride; mixed sulfonic acid anhydrides method) and symmetric anhydrides (obtainable, for example, by condensation of the corresponding acid in the presence of a carbodiimide or 1-diethylaminopropyne; symmetric anhydrides method). Suitable cyclic amides arc especially amides having five-membereddiazacycles of aromatic character, such as amides with imidazoles, for example imidazole (obtainable, for example, by treatment of the corresponding acid with N,N' -carbonyldiimidazole; imidazole method), or pyraz»le, for example 3,5-dimethylpyrazole (obtainable, for example, via the acid hydrazide by tieatment with acetylacetone; pyrazolide method). As mentioned, carboxylic acid derivatives that are used as acylating agents can also be formed in situ. For example, N,N'-disubstituted amidino esters can be formed in situ by reacting a mixture of the starting material of formula IV and the acid of formula V used as acylating agent, in the presence of a suitable NjN'-disubstituted carbodiimide, for example N,N'-cyclohexylcarbodiimide, the reaction being carried out, for example, in the presence -63- of a suitable base, such as triethylamine. In addition, amino or amido esters of the acids used as acylating agents can be formed in the presence of the starting material of formula IV to be acylated, by reacting a mixture of the corresponding acid and amino starting materials in the presence of an N^N'-disubstituted carbodiimide, for example N,N'-dicyclohexylcarbodiimide, and of an N-hydroxyamine or N-hydroxyamide, for example N-hydroxysuccinimide, where appropriate in the presence of a suitable base, for example 4-dimethylamino-pyridine. Moreover, activation in situ can be achieved by reaction with N,N,N',N'-tetraalkyluxonium compounds, such as O-benzotriazol-1 -yl-N,N,N' ,N'-tetramethyluronium hexafluorophosphate. Finally, phosphoric acid anhydrides of the carboxylic acids of formula V can be prepared in situ by reacting an alkyl-phosphoric acid amide, such as hexamethylphosphoric acid triamide, in the presence of a sulfonic acid anhydride, such as 4-toluenesulfonic acid anhydride, with a salt, such as a tetrafluoroborate, for example sodium tetrafluoroborate, or with another derivative of hexamethylphosphoric acid triamide, such as benzotriazol- lyloxy-tris(dimethylamino)-phosphonium hexafluoridc, preferably in the presence of a racemisation-reducing additive, such as N-hydroxybenzotriazole. The amino group of compounds of formula IV that participates in the reaction preferably carries at least one reactive hydrogen atom, especially when the carboxy group reacting therewith is in reactive form; the compound of formula IV may, however, itself be in the form of a reactive derivative, i.e. with the amino group in reactive form, for example by reaction with a phosphite, such as diethyl chlorophosphite, 1,2-phenylene chlorophosphite, ethyl dichlorophosphite, ethylene chlorophosphite or tetraethyl pyrophosphite. A derivative of such a compound having an amino group is, for example, also a carbamic acid halide, the amino group participating in the reaction being substituted by halo-carbonyl, for example chlorocarbonyl. Condensation to form an amide bond can be carried out in a manner known per se, for example as described in standard works such as "Houben-Weyl, Methoden der organischen Chemie", 4th edition, Volume 15/n (1974), Volume IX (1955) Volume E 11 (1985), Georg Thieme Verlag, Stuttgart, "The Peptides" (E. Gross and J. Meienhofer, eds.), Volumes 1 and 2, Academic Press, London and New York, 1979/1980, or M. Bodansky, "Principles of Peptide Synthesis", Springer-Verlag, Berlin 1984. The condensation of a free carboxylic acid with the corresponding amine can be carried out preferably in the presence of one of the customary condensation agents. Customary -64- '15 0 0 1 7 condensation agents are, for example, carbodiimides, for example diethyl-, dipropyl-, N-ethyl-N *-(3Klimethylaminopropyl)-caTbodiimide or especially dicyclohexylcarbo-diimide, also suitable carbonyl compounds, for example carbonylimidazole, 1,2-oxazol-ium compounds, for example 2-ethyl-5-phenyl-1,2-oxazolium 3'-sulfonate and 2-tert-butyl-S-methylisoxazolium perchlorate, or a suitable acylamino compound, for example 2-ethoxy-1 -ethoxycarbonyl-1,2-dihydroquinoline, N,N,N\N'-tetraalkyluronium compounds, such as O-benzotriazol-1 -yl-N,N,N* ,N'-tetramethyluronium hexafluoro-phosphate, also activated phosphoric acid derivatives, for example diphenylphosphoryl azide, diethylphosphoryl cyanide, phenyl-N-phenylphosphoroamidochloridate, bis(2-oxo- 3-oxazolidinyl)phosphinic acid chloride or 1 -benzotriazolyloxy-tris(dimethylamino) -phosphonium hexafluorophosphate. If desired, an organic base is added, for example a tri-lower alkylamine having bulky radicals, for example ethyl diisopiopylamine, and/or a heterocyclic base, for example pyridine, 4-dimethylaminopyridine or preferably N-methylmorpholine. The condensation of activated esters, reactive anhydrides or reactive cyclic amides with the corresponding amines is customarily carried out in the presence of an organic base, for example simple tri-lower alkylamines, for example triethylamine or tributylamine, or one of the above-mentioned organic bases. If desired, a condensation agent is additionally used, for example as described for free carboxylic acids. Hie condensation of acid anhydrides with amines can be effected, for example, in the presence of inorganic carbonates, for example ammonium or alkali metal carbonates or hydrogen carbonates, such as sodium or potassium carbonate or hydrogen carbonate (customarily together with a sulfate), and the reaction of sulfonic acid halides, such as sulfonic acid chlorides, can be effected in the presence of hydroxides, for example alkali metal hydroxides, such as sodium hydroxide or potassium hydroxide. Carboxylic acid halides, for example the chlorocarbonic acid derivative derived from the acid of formula V, are condensed with the corresponding amines preferably in the presence of an organic amine, for example the above-mentioned tri-lower alkylamines or heterocyclic bases, where appropriate in die presence of a hydrogen sulfate. The condensation is preferably carried out in an inert, aprotic, preferably anhydrous, solvent or solvent mixture, for example in a carboxylic acid amide, for example -65- farm amide or dimethylfonnamide, a halogenated hydrocarbon, for example methylene chloride, carbon tetrachloride or chlorobenzene, a ketone, for example acetone, a cyclic ether, for example tetrahydrofuran, an ester, for example ethyl acetate, or a nitrile, for example acetonitrile, or in a mixture thereof, as appropriate at reduced or elevcti^d temperature, for example in a temperature range of from approximately -40°C to approximately +100°C, preferably from approximately -10°C to approximately +50°C, and without an inert gas or under an inert gas atmosphere, for example a nitrogen or argon atmosphere. Aqueous, for example alcoholic, solvents, for example ethanol, or aromatic solvents or mixtures of solvents, for example benzene or toluene, may also be used. When alkali metal hydroxides are present as bases, acetone may also be added where appropriate. The condensation can also be carried out in accordance with the technique known as solid phase synthesis which originates from R. Merrifield and is described, for example, in Angew. Chem. 97,801 - 812 (1985), Naturwissenschaften 71,252 - 258 (1984) or in R. A. Houghten, Proc. Natl. Acad. Sci. USA 82,5131 - 5135 (1985). Functional groups protected by protecting groups in the resulting compounds of formula I having protected functions are freed where appropriate in accordance with one or more of the methods mentioned under Process a). A starting compound of formula IV is preferably prepared from a compound of formula VI, which can be prepared as described under Process c), by amidation either with L-asparagine N-protected by an amino-protecting group P2, for example a-(N-benzyloxy-caxbonyl)-L-asparagine, or with a reactive acid derivative thereof, especially the p-nitro-phenyl ester, preferably in the presence of a tertiary nitrogen base, such as triethylamine or N-ethyldiisopropylamine, as described above, especially in an acid amide, for example dimethylfonnamide, at temperatures of from 0 to 50°C, preferably at room temperature, there being obtained the compound of formula IV N-protected by P2, which compound is converted into the compound of formula IV by removal of the protecting group P2 under the conditions mentioned for the removal of protecting groups from a compound of formula IX. 25 0 0 1 -66- Process c) Amidation (Condensation to form an amide bond) In starting materials of formulae VI and/or VII, functional groups that are not intended to participate in the reaction are protected if necessary by protecting groups. The protecting groups and the introduction thereof are as described above under Process a). The free carboxylic acids and die reactive derivatives thereof and the processes used for amidation (condensation) are totally analogous to those described under Process b), except that amino compounds of formula VI are used instead of those of formula IV and carboxylic acids of formula VII are used instead of those of formula V. Functional groups protected by protecting groups in the resulting compounds of formula I having protected functions are freed where appropriate in accordance with one or more of the methods mentioned under Process a). It should be noted that this reaction may possibly be obstructed by acyl migration of the radical to the free amino group in the compound of formula VL The process variant is therefore preferably restricted to those starting materials and reaction conditions that allow reaction to take place without troublesome acyl migration. A starting compound of formula VI is preferably prepared by reacting a compound of the above-defined formula IX with a carboxylic acid of formula HI, which is likewise defined above, or with a reactive derivative thereof, under reaction conditions analogous to those described for Process a), there being obtained a Pj-protected derivative of a compound of formula VI from which the protecting group, for example tert-butoxycarbonyl or benzyloxycarbonyl, is removed, preferably as described for the removal of protecting groups from a compound of formula IX, to yield the compound of formula VI. A starting compound of formula VII is obtained, for example, by amidating with quinoline-2-carboxylic acid a carboxy-protected derivative of L-asparagine (protected, for example, by one of the protecting groups for protected carboxy mentioned under Process a)) under the above-mentioned amidation conditions, preferably the conditions mentioned above for the preparation of compounds of formula II from a compound of formula X after removal of the protecting group P2, and removing the carboxy-protecting group to yield the compound of formula VII. 61- Process variant c) is preferably not used to obtain compounds of formula I; one of Processes a) and b) is preferably used instead. All the other starting compounds mentioned for one of the above-mentioned processes are commercially available or known, or can be prepared in accordance with processes known per se. All the reactions mentioned can be carried out under reaction conditions known per se, preferably under the conditions mentioned above, at customary temperatures, in the presence or absence of inert solvents or diluents, for example in acid amides, for example carboxylic acid amides, such as dimethylfonnamide, dimethylacetamide or 1,3-dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidinone (DMPU), or amides of inorganic acids, such as hexamethylphosphoric acid triamide, ethers, for example cyclic ethers, such as tetrahydrofuran or dioxane, or cyclic ethers, such as diethyl ether or ethylene glycol dimethyl ether, halogenated hydrocarbons, such as halo-lower alkanes, for example methylene chloride or chloroform, ketones, such as acetone, nitriles, such as acetonitrile, acid anhydrides, such as acetic anhydride, esters, such as ethyl acetate, bisalkane sulfines, such as dimethyl sulfoxide, nitrogen heterocycles, such as pyridine, or mixtures of those solvents, especially in anhydrous solvents or solvent mixtures, it being possible to select for the above-mentioned reactions the particular solvents that are suitable in each case, there being used, where appropriate and expedient, salts of the compounds used, especially metal salts of carboxylic acids that are used, such as the alkali metal or alkaline earth metal salts, for example sodium or potassium salts, in the absence or presence of catalysts, condensation agents or neutralising agents and, depending on the nature of the reaction and/or the reactants, under atmospheric pressure or in a closed vessel, under normal pressure or under elevated pressure, for example at die pressure produced in the reaction mixture under the reaction conditions in a closed tube, and/or in an inert atmosphere, for example under an argon or nitrogen atmosphere. Preference is given to reaction conditions that are analogous to those mentioned in the Examples. Furthermore, the acylating agent, for example a carboxylic acid halide or a carboxylic acid anhydride, can itself serve as solvent. The course of the reaction is advantageously monitored using customary methods of analysis, especially using thin-layer chromatography. Additional Process Steps In the additional process steps, which are optional, in the starting compounds functional -68- groups that are not intended to participate in the reaction may if necessary be in protected form, for example may be protected by one or more of the protecting groups mentioned above under Process a). The protecting groups may be removed according to the methods mentioned under Process a). Salts of compounds of formula I may be prepared in a manner known per se. For example salts of compounds of formula I having acid groups may be formed, for example, by treatment with metal compounds, such as alkali metal salts of suitable organic carboxylic acids, e.g. the sodium salt of 2-ethylhexanoic acid, with organic alkali metal or alkaline earth metal compounds, such as the corresponding hydroxides, carbonates or hydrogen carbonates, such as sodium or potassium hydroxide, carbonate or hydrogen carbonate, with corresponding calcium compounds or with ammonia or a suitable organic amine, there preferably being used stoichiometric amounts or only a small excess of the salt-forming agent The preferred acid addition salts of compounds of formula I are obtained in customary manner, e.g. by treatment with an acid, for example an organic acid or an inorganic acid, or with a suitable ion exchanger. Internal salts of compounds of formula I having acid and basic salt-forming groups, e.g. a free carboxy group and a free amino group, may be formed, for example, by the neutralisation of salts, such as acid addition salts, to the isoelectric point, e.g. with weak bases, or by treatment with ion exchangers. Salts can be converted into the free compounds in customary manner, metal and ammonium salts can be converted, for example, by treatment with suitable acids or acid ion exchangers, and acid addition salts, for example, by treatment with a suitable basic agent or basic ion exchangers. The conversion of a salt of a compound of formula I into a different salt is effected, for example, by converting a salt into the free compound, as last described, and subsequently converting the free compound into a different salt, as last described, or by converting a salt directly into a different salt, for example by converting one salt into another by means of chromatography, for example by means of gel permeation chromatography, or from a solution having an excess of the oppositely charged ion required for the formation of the new salt Stereoisomers mixtures, that is mixtures of diastereoisomers and/or enantiomers, such as, for example, racemic mixtures, can be separated in a manner known per se by suitable separating methods into the corresponding isomers. For example mixtures of diastereo- -69- isomers can be separated into the individual diastereoisomers by fractional crystallisation, chromatography, solvent partition etc.. Racemates can be separated, after conversion of the optical antipodes into diastereoisomers for example by reaction with optically active compounds, e.g. optically active acids or bases, by chromatography on column materials covered with optically active compounds or by enzymatic methods, e.g. by selective reaction of only one of the two enantiomers. This separation can be carried out either at the stage of one of the starting materials or with the compounds of formula I themselves. In an obtainable compound of formula I an amino or carboxamide group may be substituted, a carboxy group that is present in free form or in reactive form may be esterified or amidated, or an esterified or amidated carboxy group may be converted into a free carboxy group. The substitution of a carboxamide group or of a primary or secondary amino group, for example to form di-lower alkylcarbamoyl or mono- or di-hydroxy-lower alkylcarbamoyl, in compounds of formula I in which the nitrogen atom of the amino groups to be reacted is bonded to hydrogen, is effected e.g. by alkylation. Suitable agents for alkylating a carboxamide group in a compound of formula I are e.g. diazo compounds, e.g. diazomethane. Diazomethane can be decomposed in an inert solvent, the free methylene formed reacting with the carboxamide group in the compound of formula I. The decomposition of diazomethane is carried out preferably by catalysis, e.g. in the presence of a noble metal in finely divided form, e.g. copper, or a noble metal salt, e.g. copper(I) chloride or copper(II) sulfate. Alkylating agents are also mentioned in German Offenlegungsschrift 2 331133, e.g. alkyl halides, sulfonic acid esters, Meerwein salts or 1-substituted 3-aryltriazenes, which can be reacted under the reaction conditions mentioned therein with a compound of formula I having a carboxamide group. Further alkylating agents are selected from corresponding unsubstituted or substituted lower alkyl compounds that serve to introduce substituted or unsubstituted lower alkyl radicals, as mentioned above for the radical Rj of an N-substituted carbamic acid, carrying an additional substituent X wherein X is a leaving group. A leaving group is especially a nucleofugal leaving group selected from hydroxy esterified by a strong inorganic or organic acid, such as hydroxy esterified by a mineral acid, e.g. a hydrohalic acid, such as -70- hydrochloric, hydrobromic or hydriodic acid, or by a strong organic sulfonic acid, such as an unsubstituted or substituted, for example halo-substituted, such as fluoro-substituted, lower alkanesulfonic acid, or an aromatic sulfonic acid, e.g. a benzenesulfonic acid that is unsubstituted or substituted by lower alkyl, such as methyl, by halogen, such as bromine, and/or by nitro, e.g. a methanesulfonic, trimethanesulfonic or p-toluenesulfonic acid, and hydroxy esterified by hydrazoic acid. For example, one of the compounds having a substituent X wherein X is a leaving group with high polarisability of die electron shell, e.g. bromine or iodine, can be reacted in a polar apiotic solvent, e.g. acetone, acetonitrile, nitromethane, dimethyl sulfoxide or dimethylfonnamide. The substitution reaction is carried out if desired at reduced or elevated temperature, e.g. in a temperature range of from approximately -40° to approximately 100°C, preferably from approximately -10° to approximately 50°C, and if desired under an inert gas, e.g. under a nitrogen or argon atmosphere. For the esterification or amidation of a carboxy group in a compound of formula I, for example for the amidation of a free carboxy group of an amino acid, such as Glu or Asp, with ammonia, lower alkylamine or di-lower alkylamine, if desired the free acid can be used or the free acid can be converted into one of the above-mentioned reactive derivatives and reacted with an alcohol, with ammonia, or with a primary or secondary amine, or, for the purpose of esterification, the free acid or a reactive salt, e.g. the caesium salt, can be reacted with a reactive derivative of an alcohol. For example the caesium salt of a carboxylic acid can be reacted with a halide or sulfonic acid ester corresponding to the alcohol. The esterification of the carboxy group can also be carried out with other customary alkylating agents, e.g. with diazomethane, alkyl halides, sulfonic acid esters, Meerwein salts or 1-substituted 3-aryltriazenes, etc.. In order to convert an esterified or amidated carboxy group into the free carboxy group, it is possible to use one of the methods described above for the removal of carboxy-protecting groups or, if desired, alkaline hydrolysis under customary reaction conditions, such as those mentioned in Qrganikum, 17th edition, VEB Deutscher Verlag der Wissen-schaften, Berlin 1988. In a compound of formula I a free amino group can be acylated, for example in order to introduce one of the radicals mentioned for Rj with the exception of hydrogen. The acylation is effected in accordance with the methods mentioned above under Process a) or ^ u (J 1 7 -71- one of the methods mentioned for protecting groups or, for example, in accordance with one of the processes mentioned in Organikum, 17th edition, VEB Deutscher Verlag der Wissenschaften, Berlin (East) 1988. In a compound of formula I wherein Rx is an aminoacyl radical having a primary or secondary a-amino group, the a-amino group can be alkylated by a radical selected from lower alkyl, phenyl-lower alkyl and heterocyclyl-lower alkyl, for example by reductive amination of the amino group of the amino acid residue (protected, if necessary, at further groups that are not intended to participate in the reaction) with a lower alkyl aldehyde or ketone, a phenyl-lower alkyl aldehyde or ketone or a heterocyclyl-lower alkyl aldehyde or ketone, for example formaldehyde, a heterocyclyl aldehyde, for example furan aldehyde, such as furan-2-aldehyde, pyridine aldehyde, such as pyridine-3-aldehyde, or imidazolyl aldehyde, such as imidazol-4-yl aldehyde (if necessary N-protected, for example by trityl which can be removed as described above from the protected compound of formula 1), for example with catalytic hydrogenation, for example in the presence of a suitable heavy metal catalyst, such as Roney nickel, under normal pressure or under pressures of from 1 to 100 bar, preferably at approximately 100 bar, or with reduction by means of complex boron hydrides, such as sodium cyanoboron hydride. In a compound of formula I wherein Rx is 2-halo-lower alkanoyl, such as chloroacetyl, the halogen atom may if necessary, especially in the case of chlorine or bromine, be converted by the Finkelstein reaction in a polar aprotic solvent, especially a ketone, such as acetone, with sodium iodide into the corresponding compound of formula I containing 2-iodo-lower alkanoyl, especially 2-iodoacetyl. A compound of formula I containing 2-halo-lower alkanoyl, especially 2-iodoacetyl, can then be converted by reaction with an amino-, Iowa: alkylamino- or di-lower alkylamino-lower alkanol or an amino-, lower alkylamino-or di-lower alkylamino-lower alkoxy-lower alkanol, preferably in the presence of bases, such as carbonates or hydrogen carbonates, for example alkali metal carbonates or hydrogen carbonates, such as sodium or potassium carbonate or sodium or potassium hydrogen carbonate, in the solvents last mentioned, or (especially in the case of 2-chloro-or 2-bromo-lower alkanoyl) the corresponding (if necessary N-protected) alkali metal alcoholates of the amino-, lower alkylamino- or di-lower alkylamino-lower alkanols or amino-, lower alkylamino- or di-lower alkylamino-lower alkoxy-lower alkanols (which can be prepared, for example, from the corresponding alcohol and an alkali metal, such as sodium or potassium, in a suitable, halogen-free aprotic solvent) into the compound of formula I wherein Rx is amino-, lower alkylamino- or di-lower alkylamino-lower alkoxy- -72- 2-lower alkanoyl, such as dimethylamino-lower alkoxyacetyl, or amino-, lower alkylamino- or di-lower alkylamino-lower alkoxy-lower alkoxy-2-lower alkanoyl, such as dimethylamino-(2-lower alkoxyethoxy) acetyL In an obtainable compound of formula 1 wherein the substituents are as defined and at least one free hydroxy group is present and the remaining functional groups are in protected form, the free hydroxy group can be acylated or etherified. The acylation can be carried out using acylating reagents in accordance with one of the methods mentioned under Processes a) to e) or in accordance with one of the methods mentioned for protecting groups, or in accordance with one of the processes mentioned in Qrganikum, 17th edition, VEB Deutscher Verlag der Wissenschaften, Berlin (East) 1988. The etherification can be carried out using the above-mentioned alkylating agents and under the same reaction conditions, for example with diazomethane, alkyl halides, sulfonic acid esters, Meerwein salts, 1-substituted 3-aryltriazines, etc.. The above-mentioned reactions can be carried out under reaction conditions that are known per se, in the absence or customarily in the presence of solvents or diluents, preferably those solvents and diluents that are inert towards the reagents used and are solvents therefor, in the absence or presence of catalysts, condensation agents or neutralising agents, depending on the nature of the reaction and/or the reactants at reduced, normal or elevated temperature, e.g. in a temperature range of from approximately -80°C to approximately 200°C, preferably from approximately -20°C to approximately 150°C, for example from room temperature to the reflux temperature, in the case of melts at up to 220°C, under atmospheric pressure or in a closed vessel, if desired undo- pressure, for example at the pressure produced in the reaction mixture under the reaction conditions in a closed tube, and/or in an inert atmosphere, e.g. under an argon or nitrogen atmosphere. The reaction conditions specifically mentioned in each case are preferred. Solvents and diluents are, for example, water, alcohols, for example lower alkyl hydroxides, such as methanol, ethanol or propanol, diols, such as ethylene glycol, triols, such as glycerol, or aryl alcohols, such as phenol, acid amides, for example carboxylic acid amides, such as dimethylfonnamide, dimethylacetamide or 1,3-dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidinone (DMPU), or amides of inorganic acids, such as hexamethylphosphoric acid triamide, ethers, for example cyclic ethers, such as tetrahydro- £ ** <j \j '§ -73- fuian or dioxane, or acyclic ethers, such as diethyl ether or ethylene glycol dimethyl ether, halogenated hydrocarbons, such as halo-lower alkanes, for example methylene chloride or chloroform, ketones, such as acetone, nitriles, such as acetonitrile, acid anhydrides, such as acetic anhydride, esters, such as ethyl acetate, bisalkane sulfines, such as dimethyl sulfoxide, nitrogen heterocycles, such as pyridine, hydrocarbons, for example lower alkanes, such as heptane, or aromatic compounds, such as benzene or toluene, or mixtures of those solvents, it being possible to select die particular solvents that are suitable for each of the above-mentioned reactions. In view of the close relationship between the compounds of formula 1 and the precursors thereof in free form and in the form of salts, hereinbefore and hereinafter any reference to the compounds and intermediates should be understood as including the corresponding salts and free compounds, respectively, as appropriate and expedient, provided that the compounds contain one or more salt-forming groups. Starting compounds and intermediates may also be present in protected form, where necessary, it being possible for the protecting groups to be removed at suitable times. Protecting groups and their removal are especially as defined above. The compounds, including their salts, may also be obtained in the form of hydrates, or their crystals may include, for example, the solvent used for crystallisation. The invention relates also to those forms of the process in which a compound obtainable as intermediate at any stage is used as starting material and the remaining steps are carried out, or the process is interrupted at any stage, or a starting material is formed under the reaction conditions or is used in the form of a reactive derivative or salt, or in which a compound obtainable according to the process of the invention is produced under the process conditions and further processed in situ. The starting materials used are preferably those that result in the compounds described above as preferred. Pharmaceutical Compositions: The invention relates also to pharmaceutical compositions comprising compounds of formula I (referred to as active ingredient). The pharmacologically acceptable compounds of the present invention may be used, e.g., for the preparation of pharmaceutical compositions that comprise an effective amount of -74- tfae active ingredient together or in admixture with a significant amount of inorganic or organic, solid or liquid, pharmaceutically acceptable carriers. The pharmaceutical compositions according to the invention are those for enteral, such as nasal, buccal, rectal or oral, or parenteral, such as intramuscular or intravenous, administration to warm-blooded animals (humans and animals), comprising an effective dose of the pharmacological active ingredient alone or together with a significant amount of a pharmaceutically acceptable carrier. The dose of the active ingredient depends on the species of warm-blooded animal, the body weight, the age and the individual condition, individual pharmacokinetic data, the disease to be treated and the method of administration. The invention relates also to pharmaceutical compositions and to a method for treating diseases caused by retroviruses, for example AIDS, especially when the disease is caused by HIV-1 or HIV-2, which comprises administering an antiretrovirally effective amount of a compound of formula 1 according to the invention, especially to a warm-blooded animal, for example a human, who requires such treatment on account of one of the mentioned diseases, especially AIDS. Hie dose to be administered to warm-blooded animals, for example humans of approximately 70 kg body weight, is from approximately 3 mg to approximately 10 g, preferably from approximately 10 mg to approximately 4 g, for example approximately from 25 mg to 2.0 g per person per day, divided preferably into 1 to 5, especially 1 to 3, single doses which may, for example, be of the same size. Usually, children receive half of the adult dose. The pharmaceutical compositions comprise from approximately 1 % to approximately 95 %, preferably from approximately 20 % to approximately 90 %, active ingredient Pharmaceutical compositions according to the invention may be, for example, in unit dose form, such as in the form of ampoules, vials, suppositories, drag6es, tablets or capsules. The pharmaceutical compositions of the present invention are prepared in a manner known per se, for example by means of conventional dissolving, lyophilising, mixing, granulating or confectioning processes. It is preferable to use solutions of the active ingredient, and also suspensions or dispersions, and especially isotonic aqueous solutions, dispersions or suspensions, it being possible, for example in the case of lyophilised compositions that comprise the active -75- ingredient alone or together with a carrier, e.g. mannitol, for such solutions, dispersions or suspensions to be prepared prior to use. The pharmaceutical compositions may be sterilised and/or may comprise excipients, e.g. preservatives, stabilisers, wetting agents and/or emulsifying agents, solubilisers, salts for regulating the osmotic pressure and/or buffers, and are prepared in a manner known per se, e.g. by means of conventional dissolving or lyophilising processes. The said solutions, dispersions or suspensions may comprise viscosity-increasing substances, such as sodium carboxymethylcellulose, carbox>methylcellulose, dextran, polyvinylpyrrolidone or gelatin. Suspensions in oil comprise as the oil component the vegetable, synthetic or semisynthetic oils customary for injection purposes. There may be mentioned as such especially liquid fatty acid esters that contain as the acid component a long-chained fatty acid having from 8 to 22, especially from 12 to 22, carbon atoms, e.g. lauric acid, tridecylic acid, myristic acid, pentadecylic acid, palmitic acid, margaric acid, stearic acid, arachidic acid, behenic acid or corresponding unsaturated acids, e.g. oleic acid, elaidic acid, erucic acid, brassidic acid or linoleic acid, if desired with the addition of antioxidants, e.g. vitamin E, P-carotene or 3,5-di-tert-butyl-4-hydroxytoluene. The alcohol component of those fatty acid esters has a maximum of 6 carbon atoms and is a mono- or poly-hydric, e.g. a mono-, di- or tri-hydric, alcohol, e.g. methanol, ethanol, propanol, butanol or pentanol or the isomers thereof, but especially glycol and glycerol. The following examples of fatty acid esters are therefore to be mentioned: ethyl oleate, isopropyl myristate, isopropyl palmitate, "Labrafil M 2375" (polyoxyethylene glycerol trioleate, Gattefoss6, Paris), "Miglyol 812" (triglyceride of saturated fatty acids with a chain length of Cg to C^. Hiils AG, Germany), but especially vegetable oils, such as cottonseed oil, almond oil, olive oil, castor oil, sesame oil, soybean oil and more especially groundnut oil The injection compositions are prepared in customary manner under sterile conditions; the same applies also to introducing the compositions into ampoules or vials and sealing the containers. Pharmaceutical compositions for oral administration can be obtained by combining the active ingredient with solid carriers, if desired granulating a resulting mixture, and processing the mixture, if desired or necessary, after the addition of appropriate excipients, into tablets, dragee cores or capsules, or by preparing dispersions, preferably with phospholipids, which are introduced into vials. It is also possible for the active ingredients -76- to be incorporated into plastics carriers that permit the active ingredients to be diffused or released in measured amounts. Suitable carriers are especially fillers, such as sugars, e.g. lactose, saccharose, mannitol or sorbitol, cellulose preparations and/or calcium phosphates, e.g. tricalcium phosphate or calcium hydrogen phosphate, and binders, such as starch pastes using e.g. com, wheat, rice or potato starch, gelatin, tragacanth, methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidone, and/or, if desired, disintegrators, such as the above-mentioned starches, also carboxymethyl starch, crosslinked polyvinylpyrrolidone, agar, alginic acid or a salt thereof, such as sodium alginate. Excipients are especially flow conditioners and lubricants, e.g. silicic acid, talc, stearic acid or salts thereof, such as magnesium or calcium stearate, and/or polyethylene glycol. Drag6e cores are provided with suitable, optionally enteric, coatings, there being used, inter alia, concentrated sugar solutions which may comprise gum arabic, talc, polyvinylpyrrolidone, polyethylene glycol and/or titanium dioxide, or coating solutions in suitable organic solvents, or, for the preparation of enteric coatings, solutions of suitable cellulose preparations, such as ethylcellulose phthalate or hydroxypropylmethylcellulose phthalate. Capsules are dry-filled capsules made of gelatin and soft sealed capsules made of gelatin and a plasticiser, such as glycerol or sorbitol. The dry-filled capsules may comprise the active ingredient in the form of granules, e.g. with fillers, such as lactose, binders, such as starches, and/or glidants, such as talc or magnesium stearate, and if desired with stabilisers. In soft capsules the active ingredient is preferably dissolved or suspended in suitable oily excipients, such as fatty oils, paraffin oil or liquid polyethylene glycols, it likewise being possible for stabilisers and/or antibacterial agents to be added. Dyes or pigments may be added to the tablets or drag6e coatings or the capsule casings, e.g. for identification purposes or to indicate different doses of active ingredient. Especially preferred as pharmaceutical compositions are phospholipid-stabilised dispersions of the active ingredient, preferably for oral administration, comprising a) a phospholipid or several phospholipids of the formula -77- 3CH2—o— P—O — (A) O .© (CnHzn)—N—Rb N wherein RA is Cio_2oacyl» Rg is hydrogen or C10_2(>acyl, R^, Rb and R<. are hydrogen or Chalky 1 and n is an integer from two to four, if desired b) a further phospholipid or several further phospholipids c) the active ingredient and d) a pharmaceutically acceptable carrier liquid and if desired further excipients and/or preservatives. The process for the preparation of those dispersions is as follows: a solution or suspension of components a) and c) or a), b) and c), but preferably of a) and b) in a ratio by weight of from 20:1 to 1:5, especially from 5 : 1 to 1:1, is converted into a dispersion by dilution with water and the organic solvent is then removed, for example by centrifugation, gel filtration, ultrafiltration or especially by dialysis, for example tangential dialysis, preferably against water, and then, preferably after the addition of excipients or preservatives and if necessary with the establishment of an acceptable pH-value by the addition of pharmaceutically acceptable buffers, such as phosphate salts or organic acids (pure or dissolved in water), such as acetic acid or citric acid, preferably from pH 3 to 6, for example pH 4 - 5, the dispersion obtained is concentrated (unless it already has the correct active ingredient concentration) preferably to an active ingredient concentration of from 2 to 30 mg/ml, especially from 10 to 20 mg/ml, concentration preferably being effected in accordance with the methods last mentioned for the removal of an organic solvent, especially by ultrafiltration, for example using an apparatus for carrying out tangential dialysis and ultrafiltration. The phospholipid-stabilised dispersion that can be prepared in accordance with that process is stable for at least several hours at room temperature, is reproducible as regards the proportions of the components and is toxicologically acceptable and is therefore especially suitable for oral administration to humans. The size of the particles obtained in the dispersion is variable and is preferably from W \J * ■; a -78- approx. 1.0 x 10"8 to approx. 1.0 x 10"5 m, especially from approximately 10"7 to approximately 2 x 10"6 m. The nomenclature for the phospholipids of formula I and. the numbering of the carbon atoms are in accordance with the recommendations of the IUPAC-IUB Commission on Biochemical Nomenclature (CBN) (sn-nomenclature, stereospecific numbering) given in the Eur. J. of Biochem. 79,11-21 (1977) "Nomenclature of Lipids". In a phospholipid of formula A, RA and RB having the definitions Cio-20acyl816 preferably straight-chained C10.2oalkanoyl having an even number of carbon atoms and straight-chained C^oalkenoyl having a double bond and an even number of carbon atoms. Straight-chained Cj^joalkanoyl RA and Rb having an even number of carbon atoms are, for example, n-dodecanoyl, n-tetradecanoyl, n-hexadecanoyl or n-octadecanoyL Straight-chained Cio.2oalkenoyl RA and RB having a double bond and an even number of carbon atoms are, for example, 6-cis-, 6-trans-, 9-cis- or 9-trans-dodecenoyl, -tetra-decenoyl, -hexadecenoyl, -octadecenoyl or -icosenoyl, especially 9-cis-octadecenoyl (oleoyl). In a phospholipid of formula A, n is an integer from two to four, preferably two. The group of the formula -(CqEI^- is unbranched or branched alkylene, for example 1,1-ethyl-ene, 1,1-, 1,2- or 1,3-propylene or 1,2-, 1,3- or 1,4-butylene. 1 ^-Ethylene (n=2) is preferred. Phospholipids of formula A are, for example, naturally occurring cephalins wherein Ra> Rb and Rc are hydrogen, or naturally occurring lecithins wherein R*, Rb and R<. are methyl, for example cephalin or lecithin from soybeans, bovine brain, bovine liver or hen's eggs having different or identical acyl groups RA and RB or mixtures thereof. / Synthetic, substantially pure phospholipids of formula A having different or identical acyl groups Ra and RB are preferred. The term "synthetic" phospholipid of formula A defines phospholipids that have a uniform composition as regards RA and RB. Such synthetic phospholipids are preferably the 25 0 0 1 -79- lecithins and cephalins defined below, the acyl groups RA and Rg of which have a defined structure and are derived from a defined fatty acid having a degree of purity higher than approx. 95 %. RA and Rg may be identical or different and may be unsaturated or saturated. RA is preferably saturated, for example n-hexadecanoyl, and RB is preferably unsaturated, for example 9-cis-ottadecenoyl (= oleoyl). The term "naturally occurring" phospholipids of formula A defines phospholipids that do not have a uniform composition as regards RA and RB. Such natural phospholipids are likewise lecithins and cephalins the acyl groups RAand RB of which are structurally undefinable and are derived from naturally occurring fatty acid mixtures. The term "substantially pure" phospholipid defines a degree of purity of more than 70 % (by weight) of the phospholipid of formula A, which can be detected by suitable determination methods, for example by paper chromatography. Special preference is given to synthetic, substantially pure phospholipids of formula A wherein RA is straight-chained Cio.2oalkanoyl having an even number of carbon atoms and Rb is straight-chained C^ioalkenoyl having a double bond and an even number of carbon atoms. R*, Rj, and R<. are methyl and n is two. In an especially preferred phospholipid of formula A, RA is n-dodecanoyl, n-tetra-decanoyl, n-hexadecanoyl or n-octadecanoyl and RB is 9-cis-dodecenoyl, 9-cis-tetra-decenoyl, 9-cis-hexadecenoyl, 9-cis-octadecenoyl or 9-cis-icosenoyl. R,, Rb and Rc are methyl and n is two. A very especially preferred phospholipid of formula A is synthetic 1-n-hexadecanoyl-2-(9-cis-octadecenoyl)-3-sn-phosphatidyl choline having a purity of more than 95 %. Preferred natural, substantially pure phospholipids of formula A are especially lecithin (L-a-phosphatidyl choline) from soybeans or hen's eggs. The terms given in brackets are also customarily used for the acyl radicals in the phospholipids of formula A: 9-cis-dodecenoyl (lauroleoyl), 9-cis-tetradecenoyl (myrist-oleoyl), 9-cis-hexadecenoyl (palmitoleoyl), 6-cis-octadecenoyI (petroseloyl), 6-trans-octa-decenoyl (petroselaidoyl), 9-cis-octadecenoyl (oleoyl), 9-trans-octadecenoyl (elaidoyl), 11-cis-octadecenoyl (vaccenoyl), 9-cis-icosenoyl (gadoleoyl), n-dodecanoyl (lauroyl), P R n r'l - *"• ^ w \J -80- n-tetradecanoyl (myristoyl), n-hexadecanoyl (palmitoyl), n-octadecanoyl (stearoyl), n-icosanoyl (aracMdoyl). Other phospholipids arc preferably asters of phosphatidic acid (3-sn-phosphatidic acid) with the mentioned acyl radicals, such as phosphatidyl serine and phosphatidyl ethanolamine. Sparingly soluble active ingredients may also be present in the form of water-soluble, pharmaceutically acceptable salts, as defined above. The carrier liquid d) comprises the components a), b) and c) or a) and c) as liposomes in such a manner that for a period of from several days up to several weeks no solids or solid aggregates, such as micelles, re-form and the liquid comprising the said components can be administered, preferably orally, if necessary after filtration. The carrier liquid d) may comprise pharmaceutically acceptable, non-toxic excipients, for example water-soluble excipients that are suitable for producing isotonic conditions, for example ionic additives, such as sodium chloride, or non-ionic additives (structure formers), such as sorbitol, mannitol or glucose, or water-soluble stabilisers for the liposome dispersion, such as lactose, fructose or sucrose. In addition to the water-soluble excipients, the carrier liquid may also comprise emulsifiers, wetting agents or surfactants that can be used for liquid pharmaceutical formulations, especially emulsifiers, such as oleic acid, non-ionic surfactants of the fatty acid polyhydroxy alcohol ester type, such as sorbitan monolaurate, monooleate, mono-stearate or monopalmitate, sorbitan tristearate or trioleate, polyoxyethylene adducts of fatty acid polyhydroxy alcohol esters, such as polyoxyethylene sorbitan monolaurate, monooleate, monostearate, monopalmitate, tristearate or trioleate, polyethylene glycol fatty acid esters, such as polyoxyethyl stearate, polyethylene glycol-400-stearate, polyethylene glycol-2000-stearate, especially ethylene oxide/propylene oxide block polymers of the Pluronic® type (Wyandotte Chem. Corp.) or the Synperonic® type (ICI). Preferred preservatives are, for example, antioxidants, such as ascorbic acid, or micro-bicides, such as sorbic acid or benzoic acid. The following Examples serve to illustrate the invention but do not limit the scope thereof -81- in any way. Temperatures are given in degrees Celsius (°C). Where no temperature is specified, the reaction takes place at room temperature. The Rf values, which indicate the ratio of the seepage propagation of the substance in question to the seepage propagat a of the eluant front, are determined on thin layer silica gel plates by thin layer chromatography (TLQ in the following solvent systems: A ethyl acetate B methylene chloride/ethanoVtriethylamine 90:10:2 C methylene chlorideAHF 1:1 The abbreviation "Rf(A)", for example, indicates that the Rf value was determined in solvent system A. The ratio of solvents and eluants to one another is always given in parts by volume. HPLC gradients: I 20 % -*■100 % a) in b) for 35 min. II 20 % -* 100 % a) in b) for 20 min. Eluant a): acetonitrile + 0.05 % TFA; eluant b): water + 0.05 % TFA. Column (250 x 4.6 mm) filled with "Reversed-Phase" material C18-Nucleosil® (5 jtm average particle size, silica gel covalently derivatised with octadecylsilanes, Macherey & Nagel, DUren, FRG). Detection by UV-absoiption at 215 nm. The retention times (tRet) are given in minutes. Flow rate 1 ml/min. The other short forms and abbreviations used have the following meanings: abs. absolute (indicates that the solvent is anhydrous) atm physical atmospheres (unit of pressure) - 1 atm corresponds to 1.013 bar Boc tert-butoxycarbonyl BOP benzotriazol-l-yloxy-tris(dimethylamino)- phosphonium hexafluorophosphate brine saturated sodium chloride solution 0 £ tmm V -82- DIPE diisopropyl ether DMAP 4-dimethylaminopyridine DMF dimethylfonnamide h hours HOBt 1 -hydroxybenzotriazole HPLC high-performance liquid chromatography HV high vacuum min minute(s) MS mass spectroscopy NMM N-methylmorpholine RT room temperature TFA trifluoroacetic acid THF tetrahydrofuran TLC thin-layer chromatography Z benzyloxycarbonyl Mass spectroscopic data are obtained either by conventional MS or according to the "Fast-Atom-Bombardment" (FAB-MS) method. The mass data refer in the former case to the unprotonated molecule ion (M)+ or to the protonated molecule ion (M+H)+. The values for proton nuclear resonance spectroscopy (*H-NMR) are given in ppm (parts per million) based on tetramethylsilane as the internal standard, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, dd = double doublet Example 1: N-tert-Butyl-decahvdro-2-f2(R)-acetvloxv-4-Dhenvl-3(S')-rrN-(2-qumolvl-carbonvl)-L-asparaginvnaminolbutvn-(4aS^aS)-isoauinoline-3(S)-carboxaniide Under a nitrogen atmosphere, at RT, 2 crystals of DMAP and 17 nl (0.18 mmol) of acetic anhydride are added to a solution of 81 mg (0.12 mmol) of N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide in 2 ml of abs. THF and 50 pi (0.36 mmol) of triethylamine. After 18 h the reaction mixture is poured onto ice and extracted with 3 portions of ethyl acetate; the organic phases are washed with saturated NaHCOj solution, water and brine, dried with Na2S04 and concentrated by evaporation. Digestion of the crude product in DIPE yields the title compound: TLC Rf(A)=0.44; tRet=18.9 min; FAB-MS (M+H)+=713; XH-NMR (200 MHz, CDjOD): 1.34 (s, (I^C^C), 1.2-2.0 (m, ca. 13 H), 2.08 (s, H3CCO), 2.2-2.44 (m, 2 H), 2.6-2.8 (m, 5 H), 2.95-3.13 (m, 2 H), 4.43 250017 -83- (m, HC), 5.30 (m, HC), 6.89 (m, 1H), 7.04 (t, J=7 Hz, 2 H), 7.24 (d, J=7 Hz, 2 H), 7.70 (m, 1H), 7.85 (m, 1H), 8.02 (d, J=7 Hz, 1H), 8.17 (m, 2 H), 8.47 (d, J=7 Hz, 1H). The starting materials are prepared as follows: la) N-tert-Butvl-decahvdro-2-r2(R)-hvdroxv-4-phenvl-3(S)-rtert-butoxvcarbonvI-amino1butvll-(4aS.8aS)-isoquinoline-3(S)-carboxamide Under a nitrogen atmosphere, in an ampoule, 1.105 g (4.195 mmol) of 2(S)-[l(S)-(Boc-amino)-2-phenylethyl]-oxirane (prepared analogously to B.K. Handa, P.J. Machin, S. Redshaw, G J. Thomas - European Patent Appln. 0 346 847 (1989), but using the tert-butoxycarbonyl group instead of the benzyloxycarbonyl protecting group, or in accordance with Evans et aL, J. Org. Chem. 50,4615-4625 (1985)) and 1.18 g (4.95 mmol) of N-tert-butyl-decahydro-(4aS,8aS)-isoquinoline-3(S)-carboxamide (for preparation see KJE.B. Parkes, S. Redshaw, G J. Thomas, European Patent Appln. 0 432 694 A2 (1990)) in 21 ml of ethanol are heated for 16 h at 90°C Column chromatography (SiOj, hexane/-ethyl acetate 5:1 + 2 % triethylamine) of the evaporation residue yields the title compound: ^=18.1 min; FAB-MS (M+H)+=502; *H-NMR (200 MHz, CD3OD): 1.1-2.23 (m, 14 H), 1.26 and 1.33 (2 s, 2 (H3Q3C), 2.57-2.70 (m, 2 H), 2.73-2.84 (m, 1H), 2.93-3.14 (m, 2 H), 3.73-3.90 (m, 2 H), 7.1-7.3 (m, HC^). lb) N-tert-Butvl-decahYdro-2-r2(R)-hvdroxv-4-phenvl-3(S)-aminobutvll-(4aS.8aS)-isoquinoHne-3(S)-carboxamide » HC1 Under a nitrogen atmosphere, 0.6 g (1.2 mmol) of N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[tert-butoxycarbonylamino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide is dissolved in 12 ml of dioxane; 12 ml of 4N HC1 solution in dioxane are added thereto and the reaction mixture is stirred for 2 h at RT. Lyophilisation yields the tide compound: XH-NMR (300 MHz, CD3OD): 1.37 (s, (H3Q3C), 1.2-1.9 (m, 10 H), 1.9-2.2 (m, 4 H), 2.81-3.03 (m, 2 H), 3.14-3.27 (m, 2 H), 3.44 (m, 1H), 4.07 (m, 1H), 4.53 (m,lH), 7.27-7.43 (m.HC^). Alternative method of synthesis: The title compound in free form (not the HC1 salt) is obtained by stirring 109 mg (0.217 mmol) of the title compound from Example la), dissolved in 0.75 ml of concentrated formic acid. After 16 h at RT the formic acid is evaporated off under a high vacuum and the residue is partitioned between 3 portions of ethyl acetate, saturated NaHCOj solution and brine. Drying of the organic phases with Na2S04 and concentration by evaporation yield the tide compound: 1H-NMR (200 MHz, 9 I! ft ft .1 C J U u | -84- CD3OD): inter alia 1.32 (s, 9H); 2,27 (d, 12 Hz, 1H); 2.37 (dd, 12 Hz, 4 Hz, 1H); 2.57-2.78 (m, 3H), 2.99 (d, 12 Hz, 1H), 3.1-3.4 (m, 2H), 3.68 (m, 1H). Ic) N-tert-ButvI-decahvdro-2-r2(R)-hvdroxY-4-phenyl-3(S)-frN-benzyIoxycarbonvl-L-asparaginyl1aminolbutvn-(4aS«8aS)-isoquinoline-3(S)-carboxamide Dissolved in 13 ml of NMM 0.3N in DMF and 2.24 ml (13 mmol) of N-ethyl diisopropyl-amine, 0.624 g (1.35 mmol) of N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide • HC1 is reacted for 4 h at RT with 0.762 g (1.97 mmol) of Z-asparagine-p-nitrophenyl ester (Bachem, Bubendorf/-Switzerland). The reaction mixture is concentrated by evaporation under HV and the residue is partitioned between 3 portions of methylene chloride, 2 portions of 5 % K2CO3 solution and brine. Renewed dissolution in a small amount of DMF and precipitation with ice-cold DIPE yield the title compound: tRCt=15.7 min; FAB-MS (M+H)+=650. Id) N-tert-Butvl-decahydro-2-f2(R)-hvdroxv-4-phenvl-3(S>-ffL-asparaginvnaminol-butvll-(4aS,8aS)-isoquinoline-3(S)-carboxamide Dissolved in 20 ml of methanol, 0.69 g (1.06 mmol) of N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[[N-benzyloxycarbonyl-L-asparaginyl]amino]butyl]-(4aS98aS)-isoquino!ine-3(S)-carboxamide is hydrogenated in the presence of 140 mg of 10 % palladium on carbon under 1 atm hydrogen pressure for 5 h at RT. Filtering off the catalyst and concentration by evaporation yield the title compound: JH-NMR (300 MHz, CD3OD): 1.33 (s, (H3C)3Q, 1.2-2.24 (m, 15 H), 2.45 (dd, ^=15 Hz, J2=5 Hz, 1H), 2.55-2.80 (m, 3 H), 3.02-3.14 (m, 2 H), 3.54 (dd, Jj=8 Hz, J2=5 Hz, 1 H), 3.87 (m, 1 H), 4.22-4.32 (m, 1H), 7.1-7.34 (m, HC^). le) N-tert-Butvl-decahydro-2-r2(R)-hvdroxv-4-phenvl-3(S)-rfN-(2-quinolvl-carbonvI)-L-asparaginvllaminolbutvl1-(4aS.8aS)-isoquinoIine-3(S)-carboxamide A solution of 246 mg (1.42 mmol) of quinaldic acid, 487 mg (0.945 mmol) of N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[[L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 627 mg (1.42 mmol) of BOP and 192 mg (1.42 mmol) of HOBT is dissolved at RT in 7.5 ml of 0.3M NMM in DMF and stirred for 18 h at RT. The reaction mixture is concentrated by evaporation under HV and the residue is partitioned between 3 portions of methylene chloride, 2 portions of saturated sodium bicarbonate solution and brine. Drying of the combined organic phases over sodium sulfate, concentration by evaporation and column chromatography (Si02, methylene chloride/ethanol/acetic acid 90:10:1 —*■ methylene chloride/ethanol/NH3aq -85- 90:10:1) of the residue yield the tide compound; TLC Rf(B)=0.50; tR^^.O min; FAB-MS (M+H)+=671, :H-NMR (300 MHz, CD3OD): 1.31 (s, (H3C)3Q, 1.1-2.4 (m, 14 H), 2.6-2.9 (m, 5 H), 3.04 (m, 2 H), 3.92 (m, 1H), 4.23 (m, 1H), 4.92 (t, J=7 Hz, 1H), 6.74 (t, J=7 Hz, 1H), 6.91 (t, J=8 Hz, 2 H), 7.19 (d, J=8 Hz, 2 H), 7.69 (m, 1H), 7.84 (m, 1H), 7.99 (t, J=8 Hz, 1 H), 8.14 (d, J=9 Hz, 1H), 8.17 (d, J=9 Hz, 1H), 8.48 (d, J=9 Hz, 1H). Alternatively, the tide compound can also be prepared as follows (analogously to EP 0 432 695, published 19.06.1991, Example 3): a solution of N-(2-quinolylcarbonyl-AfSM L-asparagine and N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-aminobutyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide (which can be prepared as described in the alternative process under 1 b)) in tetrahydrofuran is cooled to -10°C and 3-hydroxy-l,2,3-benzotriazin-4(3H)-one (Fluka, Switzerland) and dicyclohexylcarbodiimide are added thereto; the mixture is stirred at the mentioned temperature for 2 h and at 20°C for a further lb h and then diluted with ethyl acetate and filtered. Hie filtrate is then washed with saturated sodium bicarbonate solution and brine and concentrated by evaporation. The residue is purified ovt; a silica gel column with 4 percent by volume methanol in dichloromethane and the title compound is obtained. Example 2: N-tert-Butvl-decahvdro-2-r2(R)-(fiiran-2-carbonyloxv)-4-phenvi-3(S)- ITN-(2-quinolvlcarbonyl)-L-asparaginvIlaminolbutvn-(4aS.8aS)-isoquinoline- 3(S)-carboxamidc A solution of 8.8 pi (0.06 mmol) of furan-2-carboxylic acid chloride, 0.5 mg of DMAP and 34 pi (0.2 mmol) of N-ethyl diisopropylamine in 5 ml of dioxane is added to 40 mg (0.06 mmol) of N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(2-quinolyl-carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide (Example le). After 2 days at RT, the reaction mixture is partitioned between 3 portions of ethyl acetate, saturated NaHCOj solution and brine. Drying of the organic phases with sodium sulfate, concentration by evaporation and column chromatography (Si02, methylene chloride/THF 5:1) yield the title compound: tRet=19.0 min; FAB-MS (M+H)+=765. Example 3: The following acyl derivatives of N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-iso-quinoline- 3 (S) -c arboxamide can be prepared analogously to one of the Examples given above or in accordance with the mentioned processes: -86- 3a)N-tert-butyl-decahydio-2-[2(R)-pivaloyloxy-4-phenyl-3(S)-[[N-(2-quinolylcaibonyl)-L-aspaxaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 3b)N-tert-butyl-dccahydro-2-[2(R)-(N-methylaminoacetyloxy)-4-phenyl-3(S)-[[N- (2-quinolylcarbonyl)-L-asparaginyl]aiiiino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carbox- amide, 3c) N-tert-bulyl-decahydro-2-[2(R)-(N-benzyloxycarbonyl-N-methyIaminoacetyloxy)- 4-phenyl-3(S)-[[N-(2-quinolylcaibonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS>-isoquino- line-3(S)-carboxamidc, 3d) N-tert-butyl-decahydro-2-[2(R)-(N-dimethylaminoacetyloxy)-4-phenyl-3(S)-[[N- (2-quinolylcaibonyl)-L-asparaginyl]ainino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carbox- amide, 3e) N-tert-butyl-decahydxo-2-[2(R)-(N-n-butyl-N-methylaminoacetyloxy)-4-phenyl- 3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline- 3(S)-carboxamide, 3f) N-tert-butyl-decahydro-2- [2(R)-(N-methyl-N-benzylaiiiinoacetyloxy)-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]aminoJbutyl]-(4aS,8aS)-isoquinoliiic-3(S)-carboxamide, 3g) N-tert-butyl-decahydro-2-[2(R)-(N-mcthyl-N-3-pyridylmethyl-aminoacetyloxy)- 4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquino- line-3(S)-carboxamide, 3h)N-tert-butyl-decahydro-2-[2(R)-(3-pyridylcarbonyloxy)-4-phenyl-3(S)-[[N-(2-quinolylcaibonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-car-boxamide, and/or 3i) N-tert-butyl-decahydro-2-[2(R)-(4-(N-moipholinyl-methyl)-benzoyloxy)-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline- 3(S)-carboxamide. -87- Example 4: The following acyl derivatives of N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(2-quinolylcaxbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquino-line-3 (S) -carboxamide can be prepared analogously to one of the Examples given above or in accordance with the mentioned processes: 4a) N-tert-butyl-decahydro~2-[2(R)-propionyloxy-4-phenyl-3(S)-[[N-(2-quinolyl-carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide; 4b) N-tert-butyl-decahydro-2-[2(R)-butyryloxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 4c) N-tert-butyl-decahydro-2-[2(R)-methylpropionyloxy-4-phenyl-3(S)-[[N-(2-quinolyl-carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 4d) N-tert-butyl-decahydro-2-[2(R)-pentanoyloxy-4~phenyl-3(S)-[[N-(2-quinolyl-carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 4e) N-tert-butyl-decahydro-2-[2(R)-octanoyloxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 4f) N-tert-butyl-decahydro-2-[2CR>decanoyloxy-4-phenyl-3(S)-[[N -(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamidc, 4g) N-tert-butyl-decahydro-2-[2(R)-dodecanoyloxy-4-phenyl-3(S)-[[N-(2-quinolyl-carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide) 4h) N-tert-butyl-decahydro 2-[2(R)-palmitoyloxy-4-phenyl-3(S)-[[N-(2-quinolyl-carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 4i) N-tert-butyl-decahydro-2-[2(R)-(3-carboxypropionyloxy)-4-phenyl-3(S)-[[N-(2-quino-lylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 4j)N-tert-butyl-decahydro-2-[2(R)-(3-methoxypropionyloxy)-4-phenyl-3(S)-[[N-(2-quino-lylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-caiboxamide, 4k)N-tert-butyl-decahydro-2-[2(R)-benzyloxyacetyloxy-4-phenyl-3(S)-[[N-(2-quinolyl- ij g -88- carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 41) N-tert-butyl-decahydro-2-[2(R)-{(S)-a-methoxy-a-phenylacetyloxy}-4-phenyl-3(S)- [[N-(2-quinolylcaibonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-car- boxamide, 4m) N-tert-butyl-decahydro-2-[2(R)-{ (R)-a-methoxy-a-phenylacetyloxy}-4-phenyl-3(S)- [[N-(2-quinolylcaxbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-car- boxamide, 4n) N-tert-butyl-decahydro-2-[2(R)-{2-(2-methoxyethoxy)acetyloxy}-4-phenyl-3(S)-[[N- (2-quinolylcaibonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carbox- amide, 4o) N-tcrt-butyl-decahydro-2- [2(R) - {n-butoxyacetyloxy} -4-phenyl-3 (S H[N- ^Kiuinolyl-carbonyty-I^asparaginyyaminolbutyll-^aS.SaSHsoquinoline-S^-carboxaniide, 4p) N-tert-butyl-decahydro-2-[2(R)-{2-(2-(2-methoxyethoxy)ethoxy)acetyloxy} -4-phe-nyl-3(S)-[[N-(2-quinolylcarboayl)-L-aspaiaginyl]amino]butyl]-(4aS,8aS)-isoqmnoline-3(S)-carboxamide, 4q)N-tert-butyl-decahydro-2-[2(R)-{2-pyridylacetyloxy}-4-phenyl-3(S)-[[N-(2-quinolyl-carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 4r) N-tert-butyl-decahydro-2-[2(R>{3-(2-pyridyl)propionyloxy}-4-phenyl-3(S)-[[N- (2-quinolylcaibonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carbox- amide, 4s)N-tert-butyl-decahydro-2-[2(R)-{4-imidazolylcarbonyloxy}-4-phenyl-3(S)-[[N- (2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carbox- amide, 4t) N-tert-bulyl-decahydro-2- [2(R)- {4-imidazolylacetyloxy} -4-phenyl- 3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]bu- tyl]-(4aS,8aS)-isoquinoline-3(S)-caiboxamide, -89- 25 00 17 4u) N-tert-butyl-decahydro-2-[2(R)- {3-(4-imidazolyl)propionyloxy} -4-phenyl-3(S)-[[N- (2-quinolylcaibonyl)-L-asparaginyl]ainino]butyl]-(4aSJ8aS)-isoquinoline-3(S)-carbox- amide, 4v) N-tert-butyl-decahydro-2-[2(R)-quinoliii-2-ylcarbonyloxy-4-phenyl- 3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline- 3(S)-carboxamide, 4w) N-tert-butyl-decahydro-2-[2(R)-phenoxyacetyloxy-4-phenyl-3(S)-[[N-(2-quinolyl-caibonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 4x)N-tert-butyl-decahydro-2-[2(R)-pyridine-4-caibonyloxy-4-phenyl-3(S)-[[N-(2-qumo-lylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, and 4y) N-tert-butyl-decahydro-2-[2(R)-pyridine-2-carbonyloxy-4-phenyl-3(S)-[[N-(2-quino lylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-caiboxamide. Example 5: The following acyl derivatives of N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(2-quinolylcaitx)nyl)-L-aspaiaginyl]amino]butyl]-(4aS,8aS)-iso-quinoline-3(S)-carboxamide can be prepared analogously to one of the Examples given above or in accordance with the mentioned processes: 5a) N-tcrt-butyl-decahydro-2-[2(R)-{l-pyrazolylacetyloxy}-4-phenyl-3(S)-[[N-(2-quino-lylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 5b)N-tert-butyl-decahydro-2-[2(R)-pyrazin-2-ylcarbonyloxy-4-phenyl-3(S)-[[N-(2-quino-lylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 5c) N-tert-butyl-decahydro-2-[2(R)-isoquinoline-3-carbonyloxy-4-phenyl- 3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline- 3(S)-carboxamide, 5d) N-tert-butyl-decahydro-2-[2(R)-aminoacetyloxy-4-phenyl-3(S)-[[N-(2-quinolyl-carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 5e)N-tert-butyl-decahydro-2-[2(R)-{CL)-pyrrolidine-2-carbonyloxy}-4-phenyl-3(S)-[[N- 2 5 0 0 -90- (2-quinolylcaxbonyl)-L-asparaginyl]airiino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carbox-amide, 5f) N-tert-butyl-decahydro-2-[2(R)-{N-(imidazolyl-4-methyl)-N-methylaminoacetoxy}- 4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-aspaiaginyl]amino]butyl]-(4aS,8aS)-isoquino- line-3(S)-caxboxamide, 5g) N-tert-butyl-decahydro-2-[2(R)-{N-(pyridin-2-ylmethyl)-N-methylamiiioacetoxy-4- phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquino- line-3(S)-carboxamide, 5h) N-tert-butyl-decahydro-2-[2(R)- {N,N-(4-dimethylaminobutyryl)oxy} -4-phenyl-3(S)- [[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-car- boxamide, 5i) N-tert-butyl-decahydro-2-[2(R)-benzoyloxy-4-phenyl-3(S)-[[N-(2-quinolylcaiboayl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 5j) N-tert-butyl-decahydro-2-[2(R)- {4-chloromethylbenzoyloxy} -4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, 5k)N-tert-butyl-decahydro-2-[2(R)-{3-(N»N-dimethylaminopropyl)oxyacetyloxy}-4-phenyl-3(S)-[[N-(2-quinolylcaibonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-iso-quinoline-3(S)-carboxamide, and 51) N-tert-butyl-decahydro-2-[2(R)-{2-[3-(N^N-diraethylaminopropoxy)ethoxy]- acetyloxy}-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]bu- tyl]-(4aS,8aS)-isoquinoline-3(S)-caiboxamide. Example 6: N-tert-Butyl-decahvdro-2-r2(R)-methoxyacetvIoxv-4-phenvl-3(SVrrN-(2-auinolvlcarbonvl)-L-asparaginvllaminolbutvll-(4aS,8aSViso-quinoline-3(S)-carboxamide Under a nitrogen atmosphere, at 0°C, 4 pi (0.046 mmol) of methoxyacetic acid chloride and 0.2 mg (0.002 mmol) of DMAP are added to a solution of 10 mg (0.015 mmol) of N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide (Example le) in 9 £ ft n L Vf vv -91- 0.24 ml of dioxane/pyridine 5:1. Since after 18 h at RT some starting material is still found with HPLC, a total of 35 pi of pyridine and 35 pi of methoxyacetic acid chloride is added again in 2 portions. When according to HPLC all the starting material has reacted, the reaction mixture is partitioned between 3 portions of ethyl acetate, saturated NaHCOj solution, water and brine, and the organic phase is dried in Na2S04 and concentrated by evaporation. The residue is digested from hexane/diisopropyl ether in an ultrasound bath and left to stand at 0°C to yield the pure title compound: tRet(II)=l 3.1 min; FAB-MS (M+H)+=743. Example 7: N-tert-Butyl-decahvdro-2-f2(R)-(pyridine-2-carbonvloxy)-4-phenvl- 3(S)-rrN-(2-auinolylcarbonvI)"L-asparaginvnaminolbutvll-(4aS.8aS)-iso- quinoline-3(S)-earboxamide Under a nitrogen atmosphere, at 0°C, a solution of 30 mg (0.24 mmol) of 2-picolinic acid (pyridine-2-carboxylic acid) in 1.6 ml of methylene chloride is treated with 20 pi (0.144 mmol) of 1 -chloro-N,N ,2-trimethyl-1 -propenamine [B. Haveaux, A. Dekoker, M. Rens, A JR. Sidani, J. Toye, L. Ghosez, M. Murakami, M. Yoshioka, and W. Nagata, Organic Syntheses 59,26 (1980)7 and. in the course of 45 min, at RT, converted into the acid chloride. Then 0.4 ml of pyridine, a catalytic amount of 4-dimethylaminqpyridine and 40 mg (0.06 mmol) of N-tert-butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-[[N-(2-quino-lylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide (Example le) are added thereto and the reaction mixture is stirred for 18 h at RT. Since according to HPLC some starting material is still present, a further 0.12 mmol of 2-picolinic acid chloride in 0.8 ml of methylene chloride as prepared above, together with 0.2 ml of pyridine, is added thereto. After a further 18 h at RT, the reaction mixture is partitioned between 3 portions of methylene chloride, 2 portions of saturated NaHC03 solution, water and brine, and the organic phases are dried with Na2S04 and concentrated by evaporation. Column chromatography (SiOz, methylene chloride/THF 1:1) and digestion from diisopropyl ether yield the pure title compound: TLC Rf(C)=0.28; tRK(lI)=13.2 min; FAB-MS (M+H)+=776. Example 8: Gelatin solution A sterile-filtered aqueous solution comprising one of the compounds of formula I mentioned in preceding Examples 1 to 7, and an additional 20 % cyclodextrin, and a sterile gelatin solution preserved with phenol are mixed together with heating under aseptic conditions in such a manner that 1.0 ml of solution having the following composition is obtained: -92- active ingredient 3 mg gelatin 150.0 mg phenol 4.7 mg disL water with 20 % cyclodextrins 1.0 ml Example 9; Sterile dry substance for In jection 5 mg of one of the compounds of formula I mentioned in preceding Examples 1 to 7 are dissolved in 1 ml of an aqueous solution containing 20 mg of mannitol and 20 % cyclodextrins as solubiliser. The solution is sterile-filtered and under aseptic conditions introduced into a 2 ml ampoule, deep-frozen and lyophilised. Before use, the lyophilisate is dissolved in 1 ml of distilled water or 1 ml of physiological saline solution. The solution is administered intramuscularly or intravenously. This formulation can also be introduced into double-chamber disposable syringes. Example 10: Nasal spray 500 mg of finely ground powder (<5.0 pm) of one of the compounds of formula I mentioned in preceding Examples 1 to7 are suspended in a mixture of 3.5 mlofMyglyol 812® and 0.08 g of benzyl alcohol. The suspension is introduced into a container having a metering valve. 5.0 g of Freon 12® are introduced underpressure through the valve into the container. By shaking, the "Freon" is dissolved in the Myglyol/benzyl alcohol mixture. The spray container contains about 100 single doses which can be administered separately. Example 11: Film-coated tablets For the preparation of 10 000 tablets each comprising 100 mg of a compound of formula I, the following constituents are processed: active ingredient 1000 g corn starch 680 g colloidal silicic acid 200 g magnesium stearate 20 g stearic acid 50 g sodium carboxymethyl starch 250 g water quantum satis A mixture of one of the compounds of formula I mentioned in preceding Examples 1 to 7, -93- 50 g of com starch and the colloidal silicic acid is processed into a moist mass with a starch paste consisting of 250 g of corn starch and 2.2 kg of demineralised water. This mass is passed through a sieve of 3 mm mesh size and dried in a fluidised bed drier for 30 min at 45°. The dried granules are pressed through a sieve of 1 mm mesh size, mixed with a previously sieved mixture (1 mm sieve) of 330 g of corn starch, the magnesium stearate, the stearic acid and the sodium carboxymethyl starch and compressed to form slightly domed tablets. Example 12: Orally administrable dispersion 1 625 mg of one of the compounds of formula I mentioned in preceding Examples 1 to 7 and 625 mg of POPC (l-palmitoyl-2-oleoyl-phosphatidyl choline = 1 -hexadecanoyl-2-(9-cis-octadecenoyl)-3-sn-phosphatidyl choline) are dissolved in 25 ml of ethanol. The solution is diluted with ten times the amount of water. For that purpose, the ethanolic solution is added dropwise at room temperature to the required amount of water at a rate of 10 ml/min. The ethanol is removed from the mixture by tangential dialysis ("Cross Flow Filtration") against 1750 ml of water (system: Minitan®, 700 cm2 polyether sulphone membrane having an exclusion limit of 100 kD, Millipore (USA)). Using the same system, the mixture is concentrated to 15 mg of active ingredient by ultrafiltration. After the addition of 1.24 mg/ml of citric acid and 1.24 mg/ml of di sodium hydrogen phosphate • 2 H20 to adjust the mixture to pH 4.2 and 1 mg/ml of sorbic acid as antimicrobial preservative, the dispersion is again concentrated to 15 mg/ml and introduced into vials, for example 20 ml vials. The dispersion particles have a diameter of 0.1 - 2 urn. The dispersions are stable at from +2 to 8°C for at least six months and are suitable for oral administration. Example 13: Orally administrable dispersion 2 Preparation is effected analogously to Example 12, but using 25 mg of the compound of fonnula I and 50 mg of POPC to prepare the ethanolic solution. Example 14: Orally administrable dispersion 3 Preparation is effected analogously to Example 12, but using 25 mg of the compound of formula I and 125 mg of POPC to prepare the ethanolic solution. Example IS: Orally administrable dispersion 4 Preparation is effected analogously to Example 12, but using 50 mg of the compound of fonnula I and 50 mg of POPC to prepare the ethanolic solution. </div>

Claims

<div class="application article clearfix printTableText" id="claims"> -94- Example 16: Orally administrable dispersion 5 Preparation is effected analogously to one of Examples 12 to IS, but using the compound of formula I and phosphatidyl choline from soya or phosphatidyl choline from egg yolk (70-100 % pure) instead of POPC to prepare the ethanolic solution. If desired, an antioxidant, such as ascorbic acid, is added in a concentration of 5 mg/ml. -95- WHAT WE CLAIM IS:

1. A compound of formula I 4-19330/A £5 0 0.12 (1) wherein Rj is acyl, or a salt thereof.

2. A compound according to claim 1 of fonnula I wherein Rj is octanoyl, decanoyl, dode-canoyl, palmitoyl, unsubstituted or substituted lower alkanoyl, lower alkenoyl or lower alkynoyl, wherein the substituents are selected from one or more radicals selected from the group consisting of hydroxy; lower alkoxy; lower alkoxy-lower alkoxy; lower alkoxy-lower alkoxy-lower alkoxy; phenoxy; naphthyloxy; phenyl-lower alkoxy; 2-halo-lower alkanoyl; (amino-, lower alkylamino- or di-lower alkylamino-)lower alkoxy-2-lower alkanoyl; (amino-, lower alkylamino- or di-lower alkylamino-)lower alkoxy-lower alkoxy-2-lower alkanoyl; lower alkanoyloxy; phenyl-lower alkanoyloxy; halogen; carboxy; lower alkoxycarbonyl; phenyl-lower alkoxycarbonyl; carbamoyl; lower alkylcarbamoyl; hydroxy-lower alkylcarbamoyl; di-lower alkylcarbamoyl; bis(hydroxy-l alkyl)carbamoyl; carbamoyl the nitrogen atom of which is a constituent of a 5- tq 7-membered heterocyclic ring that may contain a further hetero atom selected frj £5 0 0 1 7 -96 oxygen, sulfur, nitrogen and lower alkyl-substituted nitrogen; cyano; oxo; cycloalkyl; bicycloslkyl; tricycloalkyl; cycloalkenyl; bicycloalkenyl; heterocyclyl, which is a saturated, partially saturated or unsaturated ring containing from 5 to 7 ring atoms and up to four hetero atoms selected from nitrogen, sulfur and oxygen, the ring either being present as such or in benzo-, cyclopenta-, cyclohexa- or cyclohepta-fused form, heterocyclyl being unsubstituted or substituted by lower alkyl, lower alkanoyl, hydroxy, lower alkoxy, phenyl-lower alkoxy, hydroxy-lower alkyl, halogen, cyano and/or by trifluoromethyl; and of C6-C12aryl, which is unsubstituted or is mono- or poly-substituted by lower alkyl, halo-lower alkyl, halogen, hydroxy, lower alkoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above, cyano and/or by nitro; lower alkoxycarbonyl, 2-halo-lower alkoxycarbonyl, aryl-lower alkoxycarbonyl wherein aryl has from 6 to 14 carbon atoms and is unsubstituted or is mono- or poly-substituted by lower alkyl, halo-lower alkyl, halogen, hydroxy, lower alkoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above as a substituent of lower alkanoyl, cyano and/or by nitro; heterocyclyl-lower alkoxycarbonyl wherein heterocyclyl is as defined above as a substituent of lower alkanoyl; aminocarbonyl; an aminocarbonyl radical wherein the amino group carries 1 or 2 substituents selected independently of one another (a) from unsubstituted or substituted lower alkyl wherein the substituents are selected from hydroxy, lower alkoxy, phenoxy, naphthyloxy, lower alkanoyloxy, phenyl-lower alkanoyloxy, halogen, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, hydroxy-lower alkylcarbamoyl, di-lower alkylcarbamoyl, bis(hydroxy-lower alkyl)carbamoyl, cyano, oxo and C6-C12aryl which is unsubstituted or is mono- or poly-substituted by lower alkyl, halo-lower alkyl, halogen, hydroxy, lower alkoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, cyano and/or by nitro, and (b) from aryl which has from 6 to 14 carbon atoms and is unsubstituted or is mono poly-substituted by lower alkyl, halo-lower alkyl, halogen, hydroxy, lower alkoxj^fltewer alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carl mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, |5 0 0 - 97 - lower alkyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above as a substituent of lower alkanoyl, cyano and/or by nitro, not more than one of the substituents of the aminocarbonyl radical being aryl; or the residue, bonded via the a-carbonyl group, of an amino acid selected from glycine, alanine, 2-aminobutyric acid, 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, 5-aminopentano<c acid, 3-aminohexanoic acid, 4-aminohexanoic acid or 5-aminohexanoic acid, valine, norvaline, leucine, isoleucine, norleucine, serine, homoserine, threonine, methionine, cysteine, phenylalanine, tyrosine, 4-amino-phenylalanine, 4-chlorophenylalanine, 4-carboxyphenylalanine, p-phenylserine, phenyl-glycine, a-naphthylalanine, cyclohexylalanine, cyclohexylglycine, tryptophan, aspartic acid, asparagine, aminomalonic acid, aminomalonic acid monoamide, glutamic acid, glutamine, histidine, arginine, lysine, 6-hydroxylysine, ornithine, 3-aminopropanoic acid, a,Y-diaminobutyric acid and a,(3-diaminopropionic acid, it being possible for each of the mentioned amino acids to be in the D-, L- or (D,L)-form (except in cases where there is no asymmetric carbon atom), an a-amino group, if present, is unsubstituted or is mono- or di-N-alkylated by lower alkyl, by amino-lower alkyl, by phenyl- or naphthyl-amino-lower alkyl, by phenyl-lower alkyl, by diphenylmethyl, by trityl and/or by heterocyclyl-lower alkyl wherein heterocyclyl is as defined above for substituted lower alkanoyl R], and/or is N-acylated by an unsubstituted or substituted lower alkanoyl radical mentioned above in the definition of R1} by lower alkoxycarbonyl or by phenyl-lower alkoxycarbonyl; a carboxy group of the side chain is present in free form, in the form of a lower alkyl ester group, an aryl ester group or an aryl-lower alkyl ester group, wherein aryl is phenyl, 4-nitrophenyl, naphthyl, fluorenyl or biphenylyl, or in the form of a carbamoyl, a lower alkylcarbamoyl, a di-lower alkylcarbamoyl, a mono- or di-(hydroxy-lower alkylcarbamoyl or a mono- or di-(carboxy-lower alkyl)carbamoyl group, an amino group of the side chain that is not in the a-position is present in free form or in the form of mono- or di-lower alkylamino, lower alkanoylamino, amino-lower alkanoylamino, aryl-lower alkanoylamino wherein aryl has from 6 to 14 carbon atoms and is unsubstituted or substituted by lower alkyl, hydroxy, lower alkoxy, carboxy, carbamoyl or by sulfamoyl, lower alkoxycarbonylamino, arylmethoxycarbonylamino wherein aryl has from 6 to 14 carbon atoms, piperidyl-l-carbonyl, morpholinocarbonyl, thiomorpholino-carbonyl or S,S-dioxothiomorpholinocarbonyl, and/or a hydroxy group of the side chain is present in free form or in the form of a lowe alkoxy, phenyl-lower alkoxy, lower alkanoyloxy or lower alkoxycarbonyloxy or a salt thereof. 25 0 0 1 7 -98- 3. A compound according to claim 1 of formula I wherein Rj is unsubstituted or substituted lower alkanoyl, lower alkenoyl or lower alkynoyl, wherein the substituents are selected from one or more radicals selected from the group consisting of hydroxy; lower alkoxy; phenoxy; naphthyloxy; lower alkanoyloxy; phenyl-lower alkanoyloxy; halogen; carboxy; lower alkoxycarbonyl; phenyl-lower alkoxycarbonyl; carbamoyl; lower alkylcarbamoyl; hydroxy-lower alkylcarbamoyl; di-lower alkylcarbamoyl; bis(hydroxy-lower alkyl)carbamoyl; carbamoyl the nitrogen atom of which is a constituent of a 5 to 7-membered heterocyclic ring that may contain a further hetero atom selected from oxygen, sulfur, nitrogen and lower alkyl-substituted nitrogen; cyano; oxo; cycloalkyl; bicycloalkyl; tricycloalkyl; cycloalkenyl; bicycloalkenyl; heterocyclyl, which is a saturated, partially saturated or unsaturated ring containing from 5 to 7 ring atoms and up to four hetero atoms selected from nitrogen, sulfur and oxygen, the ring either being present as such or in benzo-, cyclopenta-, cyclohexa- or cyclohepta-fused form, heterocyclyl being unsubstituted or substituted by lower alkyl, lower alkanoyl, hydroxy, lower alkoxy, phenyl-lower alkoxy, hydroxy-lower alkyl, halogen, cyano and/or by trifluoromethyl; and of C6-C12aryl which is unsubstituted or is mono- or poly-substituted by lower alkyl, halo-lower alkyl, halogen, hydroxy, lower alkoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above, cyano and/or by nitro; lower alkoxycarbonyl, 2-halo-lower alkoxycarbonyl, aryl-lower alkoxycarbonyl wherein aryl has from 6 to 14 carbon atoms and is unsubstituted or is mono- or poly-substituted by lower alkyl, halo-lower alkyl, halogen, hydroxy, lower alkoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above as a substituent of lower alkanoyl, cyano and/or by nitro; heterocyclyl-lower alkoxycarbonyl wherein heterocyclyl "s as defined above as a substituent of lower alkanoyl; aminocarbonyl, an aminocarbonyl radical wherein the amino group carries 1 or 2 substituents selected independently of one another (a) from unsubstituted or substituted lower alkyl, wherein the substituents are selected from hydroxy, lower alkoxy, phenoxy, naphthyloxy, lower alkanoyloxy, phenyl-lo^f^TrTJv alkanoyloxy, halogen, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarb carbamoyl, lower alkylcarbamoyl, hydroxy-lower alkylcarbamoyl, di-lower alk *5QQ 17 -99- amoyl, bis(hydroxy-lower alkyl)carbamoyl, cyano, oxo and C6-C12aryl, which is unsubstituted or is mono- or poly-substituted by lower alkyl, halo-lower alkyl, halogen, hydroxy, lower alkoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, cyano and/or by nitro; and (b) from aryl which has from 6 to 14 carbon atoms and is unsubstituted or is mono- or poly-substituted by lower alkyl, halo-lower alkyl, halogen, hydroxy, lower alkoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, heterocyclyl-lower alkyl wherein heterocyclyl is as defined above as a substituent of lower alkanoyl, cyano and/or by nitro, not more than one of the substituents of the aminocarbonyl radical being aryl; or the residue, bonded via the a-carbonyl group, of an amino acid selected from glycine, alanine, 2-aminobutyric acid, 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, 5-aminopentanoic acid, 3-aminohexanoic acid, 4-aminohexanoic acid or 5-aminohexanoic acid, valine, norvaline, leucine, isoleucine, norleucine, serine, homoserine, threonine, methionine, cysteine, phenylalanine, tyrosine, 4-amino-phenylalanine, 4-chlorophenylalanine, 4-carboxyphenylalanine, p-phenylserine, phenyl-^ lycine, a-naphthylalanine, cyclohexylalanine, cyclohexylglycine, tryptophan, aspartic acid, asparagine, aminomalonic acid, aminomalonic acid monoamide, glutamic acid, glutamine, histidine, arginine, lysine, 8-hydroxylysine, ornithine, 3-aminopropanoic acid, a,Y-diaminobutyric acid and a,f}-diaminopropionic acid, it being possible for each of the mentioned amino acids to be in the D-, L- or (D,L)-form (except in cases where there is no asymmetric carbon atom), an a-amino group, if present, is unsubstituted or is mono- or di-N-alkylated by lower alkyl, by amino-lower alkyl, by phenyl- or naphthyl-amino-lower alkyl, by phenyl-lower alkyl, by diphenylmethyl, by trityl and/or by heterocyclyl-lower alkyl wherein heterocyclyl is as defined above for substituted lower alkanoyl Rj, and/or is N-acylated by an unsubstituted or substituted lower alkanoyl radical mentioned above in the definition of Rj, by lower alkoxycarbonyl or by phenyl-lower alkoxycarbonyl; a carboxy group of the side chain is present in free form, in the form of a lower allrvl _ ester group, an aryl ester group or an aryl-lower alkyl ester group, wherein aryl is offerf^,* £ Jr ^ 4-nitrophenyl, naphthyl, fluorenyl or biphenylyl, or in the form of a carbamoyl, sfjpwer ^ alkylcarbamoyl, a di-lower alkylcarbamoyl, a mono- or di-(hydroxy-lower alkylfl- ? „ o carbamoyl or a mono- or di-(carboxy-lower alkyl)carbamoyl group, \ an ammo group of the side chain that is not in the a-position is present in free fowgcfffiy t 25 0 0 1 7 100 the form of mono- or di-lower alkylamino, lower alkanoylamino, amino-lower alkanoylamino, aryl-lower alkanoylamino wherein aryl has from 6 to 14 carbon atoms and is unsubstituted or substituted by lower alkyl, hydroxy, lower alkoxy, carboxy, carbamoyl or by sulfamoyl, lower alkoxycarbonylamino, arylmethoxycarbonylamino wherein aryl has from 6 to 14 carbon atoms, piperidyl-1-carbonyl, morpholinocarbonyl, thiomorpholino-carbonyl or S,S-dioxothiomorpholinocarbonyl; and/or a hydroxy group of the side chain is present in free form or in the form of a lower alkoxy, phenyl-lower alkoxy, lower alkanoyloxy or lower alkoxycarbonyloxy group; or a salt of such a compound. 4. A compound according to claim 1 of formula I wherein Rj is octanoyl, decanoyl, dode-canoyl, palmitoyl, unsubstituted or substituted lower alkanoyl, wherein the substituents are selected from one to three radicals selected from the group consisting of hydroxy; lower alkoxy; lower alkoxy-lower alkoxy; lower alkoxy-lower alkoxy-lower alkoxy; phenoxy; naphthyloxy; phenyl-lower alkoxy; lower alkanoyloxy; phenyl-lower alkanoyloxy; (amino-, lower alkylamino- or di-lower alkylamino-)lower alkoxy-2-lower alkanoyl; (amino-, lower alkylamino- or di-lower alkylamino-)lower alkoxy-lower alkoxy-2-lower alkanoyl; halogen; carboxy; lower alkoxycarbonyl; phenyl-lower alkoxycarbonyl; carbamoyl; lower alkylcarbamoyl; hydroxy-lower alkylcarbamoyl; di-lower alkylcarbamoyl; bis(hydroxy-lower alkyl^rbamoy1, cyano; oxo; Cj-Cgcycloalkyl; C4-C8cycloalkenyl; pyrrolyl, 2,5-dihydropyrrolyl, furanyl, ttoienyl, tetrahydrofuranyl, pyrrolidinyl, imidazolyl, imidazolidinyl, pyrazolyl, pyrazolidinyl, tetrahydro-oxazolyl, tetrahydro-isoxazolyl, tetrahydro-thiazolyl, tetrahydro-isothiazolyl, indolyl, isoindolyl, quinolyl, isoquinolyl, benzimida -olyl, benzofuranyl, pyridyl, pyrimidinyl, piperidinyl, piperazin-l-yl, morphc';;>, thiomorpholino, S,S-di-oxothiomorpholino, 1,2-dihydro- or 1,2,3,4-tetrahydro-quinolyl or 1,2-dihydro- or 1,2,3,4-tetrahydro-isoquinolyl, said heterocyclic radicals being unsubstituted or substituted by lower alkyl, lower alkanoyl, hydroxy, lower alkoxy, phenyl-lower alkoxy, hydroxy-lower alkyl, halogen, cyano and/or by trifluoromethyl; and of aryl selected from phenyl, naphthyl, indanyl, indenyl and fluorenyl, those radicals being unsubstituted or mono- or poly-substituted by lower alkyl, halo-lower alkyl, halogen, hydroxy, lower alkoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, piperidinomethyl, piperazin-l-ylmethyl, 4-lower j piperazin-l-ylmethyl, 4-lower alkanoyl-piperazin-l-ylmethyl, morpholinom| morpholinomethyl, cyano and/or by nitro; 25 0 0 17 -101 - or the residue, bonded via the a-carbonyl group, of an amino acid selected from glycine, alanine, 2-aminobutyric acid, 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, 5-aminopentanoic acid, 3-aminohexanoic acid, 4-aminohexanoic acid or 5-aminohexanoic acid, valine, norvaline, leucine, isoleucine, norleucine, serine, homoserine, threonine, methionine, cysteine, phenylalanine, tyrosine, 4-amino-phenylalanine, 4-chlorophenylalanine, 4-carboxyphenylalanine, p-phenylserine, phenyl-glycine, a-naphthylalanine, cyclohexyialanine, cyclohexylglycine, tryptophan, aspartic acid, asparagine, aminomalonic acid, aminomalonic acid monoamide, glutamic acid, glutamine, histidine, arginine, lysine, 8-hydroxylysine, ornithine, 3-aminopropanoic acid, a,y-diaminobutyric acid and a,p-diaminopropionic acid, it being possible for each of the mentioned amino acids to be in the D-, L- or (D,L)-configuration (except in cases where there is no asymmetric carbon atom), an a-amino group, if present, is unsubstituted or is mono- or di-N-alkylated by lower alkyl, by amino-lower alkyl, by phenyl- or naphthyl-amino-lower alkyl, by phenyl-lower alkyl, by diphenylmethyl, by trityl, by furanyl-lower alkyl, by thienyl-lower alkyl, by imidazolyl-<ower alkyl and/or by 2-, 3- or 4-pyridyl-lower alkyl, and/or is N-acylated by an unsubstituted or substituted lower alkanoyl radical mentioned above in the definition of Rj, by lower alkoxycarbonyl or by phenyl-lower alkoxycarbonyl; or a pharmaceutically acceptable salt thereof. 5. A compound according to claim 1 of formula I wherein Rj is unsubstituted or substituted lower alkanoyl, wherein the substituents are selected from one to three radicals selected from the group consisting of hydroxy; lower alkoxy; phenoxy; naphthyloxy; lower alkanoyloxy; phenyl-lower alkanoyloxy; halogen; carboxy; lower alkoxycarbonyl; phenyl-lower alkoxycarbonyl; carbamoyl; lower alkylcarbamoyl; hydroxy-lower alkylcarbamoyl; di-lower alkylcarbamoyl; bis(hydroxy-lower alkyl)carbamoyl; cyano; oxo; C3-C8cyclo-alkyl; C4-C8cycloalkenyl; pyrrolyl, 2,5-dihydropyrrolyl, furanyl, thienyl, tetrahydrofuranyl, pyrrolidinyl, imidazolyl, imidazolidinyl, pyrazolyl, pyrazolidinyl, tetrahydro-oxazolyl, tetrahydro-isoxazolyl, tetrahydro-thiazolyl, tetrahydro-isothiazolyl, indolyl, isoindolyl, quinolyl, isoquinolyl, benzimidazolyl, benzofuranyl, pyridyl, pyrimidinyl, piperidinyl, piperazin-l-yl, morpholino, thiomorpholino, S,S-di-oxothiomorpholino, 1,2-dihydro- or 1,2,3,4-tetrahydro-quinolyl or 1,2-dihydro- or 1,2,3,4-tetrahydro-isoquinolyl, said heterocyclic radicals being unsubstituted or substituted by lower alkyl, lower alkanoyl, hydroxy, lower alkoxy, phenyl-lower a hydroxy-lower alkyl, halogen, cyano and/or by trifluoromethyl; and of aryl selected 25 0 0 1 7 -102- phenyl, naphthyl, indanyl, indenyl and fluorenyl, those radicals being unsubstituted or mono- or poly-substituted by lower alkyl, halo-lower alkyl, halogen, hydroxy, lower alkoxy, lower alkanoyloxy, carboxy, lower alkoxycarbonyl, phenyl-lower alkoxycarbonyl, carbamoyl, mono- or di-lower alkylcarbamoyl, mono- or di-hydroxy-lower alkylcarbamoyl, halo-lower alkyl, piperidinomethyl, piperazin-l-ylmethyl, 4-lower alkyl-piperazin-l-ylmethyl, 4-lower alkanoyl-piperazin-l-ylmethyl, morpholinomethyl, thiomorpholinomethyl, cyano and/or by nitro; or the residue, bonded via the a-carbonyl group, of an amino acid selected from glycine, alanine, 2-aminobutyric acid, 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, 5-aminopentanoic acid, 3-aminohexanoic acid, 4-amino-hexanoic acid or 5-aminohexanoic acid, valine, norvaline, leucine, isoleucine, norleucine, serine, homoserine, threonine, methionine, cysteine, phenylalanine, tyrosine, 4-amino-phenylalanine, 4-chlorophenylalanine, 4-carboxyphenylalanine, p-phenylserine, phenyl-glycine, a-naphthylalanine, cyclohexylalanine, cyclohexylglycine, tryptophan, aspartic acid, asparagine, aminomalonic acid, aminomalonic acid monoamide, glutamic acia, glutamine, histidine, arginine, lysine, 5-hydroxylysine, ornithine, 3-aminopropanoic acid, а,Y-diaminobutyric acid and a,p-diaminopropionic acid, it being possible for each of the mentioned amino acids to be in the D-, L- or (D,L)-configuration (except in cases where there is no asymmetric carbon atom), wherein an a-amino group, if present, is unsubstituted or is mono- or di-N-alkylated by lower alkyl, by amino-lower alkyl, by phenyl- or naphthyl-amino-lower alkyl, by phenyl-lower alkyl, by dipheay'imethyl, by trityl, by furanyl-lower alkyl, by thienyl-lower alkyl and/or by 2-, 3- or 4-pyridyl-Lower alkyl, and/or is N-acylated by an unsubstituted or substituted lower alkano.; ? radical mentioned above in the definition of Rj, by lower alkoxycarbonyl or by phenyl-lower alkoxycarbonyl; or a pharmaceutically acceptable salt thereof. б. A compound of formula I according to claim 1 wherein Rj is octanoyl, decanoyl, dode-canoyl, palmitoyl, lower alkanoyl, hydroxy-lower alkanoyl, lower alkoxy-lower alkanoyl, lower alkoxy-lower alkoxy-lower alkanoyl, lower alkoxy-lower alkoxy-lower alkoxy-lower alkanoyl, phenoxy-lower alkanoyl, phenyl-lower alkoxy-lower alkanoyl, (amino-, lower alkylamino- or di-lower alkylamino-)lower a'ioxy-2-lower alkanoyl, (amino-, lower alkylamino- or di-lower alkylamino-lower alkoxy-lower alkoxy-2-lower alkanoyl, lowe alkanoyloxy-lower alkanoyl, carboxy-Iower alkanoyl, oxo-lower alkanoyl, 5-hydn methyl-furan-2-ylcarbonyl, 2- or 3-pyrrolylcarbonyl, furylcarbonyl, thienylcarbo] pyridyl-lower alkanoyl, quinolylcarbonyl, isoquinolylcarbonyl, 2-, 3- or 5-indol 25 0 0 1 7 - 103 - pyrrolidinyl-(2- or 3-)carbonyl, 2-, 3- or 4-piperidinylcarbonyl, 1,2,3,4-tetrahydro-quinolyl-2-, -3- or -4-carbonyl, 1,2,3,4-tetrahydroisoquinolyl-l-, -3- or -4-carbonyl, imidazolyl-lower alkanoyl, pyrazolyl-lower alkanoyl, morpholinocarbonyl, thiomorpho-linocarbonyl, morpholinoacetyl, thiomorpholinoacetyl, 4-lower alkyl-1-piperazinoacetyl, indolylacetyl, benzofuranylacetyl, phenyl-lower alkanoyl that is unsubstituted or mono- or poly-substituted in the phenyl radical by lower alkyl, halo-lower alkyl, halogen, hydroxy, lower alkoxy, piperidinomethyl, piperazin-l-ylmethyl, 4-lower alkylpiperazin-l-ylmethyl, morpholinomethyl, thiomorpholinomethyl, cyano and/or by nitro; or the residue, bonded via the a-carbonyl group, of an aliphatic amino acid selected from alanine, valine, norvaline, leucine, 3-aminopropionic acid, 2-aminobutyric acid and isoleucine. or of an amino acid selected from glycine, asparagine, glutamine, methionine, lysine, phenylalanine, 3-aminobutyric acid, 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, 5-aminopentanoic acid, 3-aminohexanoic acid, 4-aminohexanoic acid and 5-aminohexanoic acid, it being possible for each of the mentioned amino acids to be in the D-, L- or (D,L)-form (except where there are no asymmetric carbon atoms), and an a-amino group, if present, is unsubstituted or is mono- or di-N-alkylated by lower alkyl, by phenyl-lower alkyl, by 2-, 3- or 4-pyridyl-lower alkyl, by imidazolyl-lower alkyl and/or by 2-, 3- or 4-pyridyl-lower alkyl, and/or is N-acylated by lower alkoxycarbonyl or by benzyloxycarbonyl, or a pharmaceutically acceptable salt thereof. 7. A compound according to claim 1 of formula I wherein R, is lower alkanoyl, hydroxy-lower alkanoyl, lower alkoxy-lower alkanoyl, phenoxy-lower alkanoyl, lower alkanoyl-oxy-lower alkanoyl, oxo-lower alkanoyl, 5-hydroxymethyl-furan-2-ylcarbonyl, 2- or

3-pyrrolylcaibonyl, furylcarbonyl, thienylcarbonyl, pyridylcarbonyl, 2-, 3- or 5-indolylcarbonyl, pyrrolidinyl-3-carbonyl, 2-, 3- or 4-piperidinylcarbonyl, l,2,3,4-tetrahydroquinolyl-2-, -3- or -4-carbonyl, 1,2,3,4-tetrahydroisoquinolyl-l-, -3- or -4-carbonyl, imidazolylcarbonyl, morpholinocarbonyl, thiomorpholinocarbonyl, morpholinoacetyl, thiomorpholinoacetyl, 4-lower alkyl-1-piperazinoacetyl, indolylacetyl, benzofuranylacetyl, phenyl-lower alkanoyl that is unsubstituted or mono- or poly-substituted in the phenyl radical by lower alkyl, halo-lower alkyl, halogen, hydroxy, lower alkoxy, piperidinomethyl, piperazin-l-ylmethyl, 4-lower alkyl-piperazin-l-ylmethyl, ,, morpholinomethyl, thiomorpholinomethyl, cyano and/or by nitro; or the radical, bor^fpf *T * B via the a-carbonyl group, of an aliphatic amino acid selected from alanine, valine, B * ^ norvaline, leucine, 3-aminopropionic acid, 2-aminobutyric acid, 3-aminobutyric a<nd^ - *>» o 4-aminobutyric acid, 3-aminopentanoic acid, 4-aminopentanoic acid, 5-aminopent 25 0 0 1 7 - 104- acid, 3-aminohexanoic acid, 4-aminohexanoic acid, 5-aminohexanoic acid and isoleucine or an amino acid selected from glycine, asparagine, glutamine, methionine, lysine, proline and phenylalanine, it being possible for each of the mentioned amino acids to be in the D-, L- or (D,L)-form (except in cases where there is no asymmetric carbon atom); an a-amino group, if present, is unsubstituted or is mono- or di-N-alkylated by lower alkyl, by phenyl-lower alkyl and/or by 2-, 3- or 4-pyridyl-lower alkyl, and/or is N-acylated by lower alkoxycarbonyl or by phenyl-lower alkoxycarbonyl, or a pharmaceutically acceptable salt thereof. 8. A compound of formula I according to claim 1 wherein R, is octanoyl, decanoyl, dode-canoyl, palmitoyl, lower alkanoyl, lower alkoxy-lower alkanoyl, lower alkoxy-lower alkoxy-lower alkanoyl, phenoxy-lower alkanoyl, phenyl-lower alkoxy-lower alkanoyl, (amino-, lower alkylamino- or di-lower alkylamino-)lower alkoxy-2-lower alkanoyl, (amino-, lower alkylamino- or di-lower alkylamino-)lower alkoxy-lower alkoxy-2-lower alkanoyl, 2-lower alkoxy-2-phenylacetyl, furylcarbonyl, pyridyl-lower alkanoyl, quinolylcarbonyl, isoquinolylcarbonyl, pyrrolidinyl-2-carbonyl, imidazolyl-lower alkanoyl, pyrazolyl-lower alkanoyl, phenyl-lower alkanoyl, 4-chloromethylbenzoyl, 4-morpholinomethylbenzoyl, 4-thiomorpholinomethylbenzoyl, aminoacetyl, N-lower alkylaminoacetyl, N,N-di-lower alkylaminoacetyl, N-lower alkyl-N-phenyl-lower alkylaminoacetyl, N-lower alkyl-N-benzyloxycarbonylaminoacetyl, N-imidazolyl-lower alkyl-N-lower alkylaminoacetyl, N-lower alkyl-N-pyridyl-lower alkylaminoacetyl or 4-(N,N-dimethylamino)butyryl, or a pharmaceutically acceptable salt thereof. 9. A compound according to claim 1 of formula I wherein Rj is lower alkanoyl, furylcarbonyl, pyridylcarbonyl, phenyl-lower alkanoyl, 4-morpholinomethylbenzoyl, 4-thiomorpholinomethylbenzoyl, aminoacetyl, N-lower alkylaminoacetyl, N,N-di-lower alkylaminoacetyl, N-lower alkyl-N-phenyl-lower alkylaminoacetyl, N-lower alkyl-N-pyridyl-lower alkylaminoacetyl or N-phenyl-lower alkoxycarbonyl-N-lower alkylaminoacetyl, or a pharmaceutically acceptable salt thereof. 10. A compound of formula I according to claim 1 wherein Rj is lower alkanoyl, lower alkoxy-lower alkanoyl, pyridylcarbonyl or furylcarbonyl, or a pharmaceutically acceptable salt thereof. 11. A compound according to claim 1 of formula I wherein Rj is lower alkano carbonyl, or a pharmaceutically acceptable salt thereof. 25 0 0 1 7 -105- 12. A compound according to claim 1 of formula I wherein R, is lower alkoxy-lower alkanoyl or pyridylcarbonyl, or a pharmaceutically acceptable salt thereof. 13. A compound according to claim 1 of formula I wherein Rj is lower alkanoyl, or a pharmaceutically acceptable salt thereof. 14. A compound of formula I according to claim 1 selected from the following compounds: N-tert-butyl-decahydro-2-[2(R)-(furan-2-carbonyloxy)-4-phenyl-3(S)-[[N-(2-quinolyl- carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-pivaloyloxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)- L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-(N-methylaminoacetyloxy)-4-phenyl-3(S)-[[N- (2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carbox- amide, N-tert-butyl-decahydro-2-[2(R)-(N-benzyloxycarbonyl-N-methylaminoacetoxy)- 4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquino- line-3(S)-carboxam ide, N-tert-butyl-decahydro-2-[2(R)-(N-dimethylaminoacetyloxy)-4-phenyl-3(S)-[[N- (2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carbox- amide, N-tert-butyl-decahydro-2-[2(R)-(N-n-butyl-N-methylaminoacetyloxy)-4-phenyl- 3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline- 3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-(N-methyl-N-benzylaminoacetyloxy)-4-phenyl- 3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline- 3(S)-carboxamide, N-tert~butyl-decahydro-2-[2(R)-(N-methyl-N-3-pyridylmethyl-aminoacetyloxy)-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquino-Hne-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-(3-pyridylcarbonyloxy)-4-phenyl-3(S)-[[N-(2-quinolyl-carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-(4-(N-morpholinyl-methyl)-benzoyloxy)-4-phen 3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoli 3(S)-carboxamide, 25 0 0 17 -106- or a pharmaceutically acceptable salt thereof. 15. A compound of formula 1 according to claim 1 selected from the following compounds: N-tert-butyl-decahydro-2-[2(R)-propionyloxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]buiyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide; N-tert-butyl-decahydro-2-[2(R)-butyryloxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)- L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-methylpropionyloxy-4-phenyl-3(S)-[[N-(2-quinolyl- carbonyl)-L-asparaginyl]amino]butylJ-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-teit-butyl-decahydro-2-[2(R)-pentanoyloxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)- L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-octanoyloxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)- L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-decanoyloxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)- I^asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-dodecanoyloxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)- L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-palmitoyloxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)- L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-(3-carboxypropionyloxy)-4-phenyl-3(S)-[[N-(2-quinolyl- carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-(3-methoxypropionyloxy)-4-phenyl-3(S)-[[N-(2-quinolyl- carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-benzyloxyacetyloxy-4-phenyl-3(S)-[[N-(2-quinolyl- carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-{(S)-a-methoxy-a-phenylacetyloxy}-4-phenyl-3(S)-[[N- (2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carbox- amide, N-tert-butyl-decahydro-2-[2(R)-{(R)-a-methoxy-a-phenylacetyloxy}-4-phenyl-3(S)-[[N- (2-quinolylcarbonyl)-I^asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carbox- amide, N-tert-butyl-decahydro-2-[2(R)-{2-(2-methoxyethoxy)acetyloxy}-4-phenyl-3(S)i (2-quinolylcarbonyl)-I^asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-amide, N-tert-butyl-decahydro-2-[2(R)-{n-butoxyacetyloxy}-4-phenyl-3(S)-[[N-(2-qu: £5 0 0 -107- carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-{2-(2-(2-methoxyethoxy)ethoxy)acetyloxy}-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-{2-pyridylacetyloxy}-4-phenyl-3(S)-[[N-(2-quinolyl- carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-{3-(2-pyridyl)propionyloxy}-4-phenyl-3(S)-[[N-(2-quino lylcarbonyI)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-{4-imidazolylcarbonyloxy}-4-phenyl-3(S)-[[N-(2-quino- lylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-{4-imidazolylacetyloxy}-4-phenyl-3(S)-[[N-(2-quinolyl- carbonyl)-L-asparaginyl]aniino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-{3-(4-imidazolyl)propionyloxy}-4-phenyl-3(S)-[[N- (2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carbox- amide, N-tert-butyl-decahydro-2-[2(R)-quinolin-2-ylcarbonyloxy-4-phenyl-3(S)-[[N-(2-quinolyl-carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-phenoxyacetyloxy-4-phenyl-3(S)-[[N-(2-quinolyl-carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-pyridine-4-carbonyloxy-4-phenyl-3(S)-[[N-(2-quinolyl-carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-pyridine-2-carbonyloxy-4-phenyl-3(S)-[[N-(2-quinolyl-carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, M-tert-butyl-decahydro-2-[2(R)-{l-pyrazolylacetyloxy}-4-phenyl-3(S)-[[N-(2-quinolyl-carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-pyrazin-2-ylcarbonyloxy-4-phenyl-3(S)-[[N-(2-quinolyl-carbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-isoquinoline-3-carbony loxy-4-phenvl-3(S)- [ [N-(2-quino-lylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-aminoacetyloxy-4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-{(L)-pyrrolidine-2-carbonyloxy}-4-phenyl-3(S)-[[N (2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-car1 amide, N-tert-butyl-decahydro-2-[2(R)-{N-(imidazolyl-4-methyl)-N-methylaminoacetylox 4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoqu 25 0 0 1 7 -108- line-3(S)-carboxamide, N-tert-butyl-dccahydro-2-[2(R)-{N-(pyridin-2-ylmethyl)-N-methylaminoacetyloxy- 4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquino- line-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-{N,N-(4-dimethylaminobutyryl)oxy}-4-phenyl-3(S)-[[N- (2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carbox- amide, N-tert-butyl-decahydro-2-[2(R)-benzoyloxy-4-p' enyl-3(S)-[[N-(2-quinolylcarbonyl)- L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-{4-chloromethylbenzoyloxy}-4-phenyl-3(S)-[[N-(2- quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline-3(S)-carboxamide, N-tert-butyl-decahydro-2-[2(R)-{3-(N,N-dimethylaminopropyl)oxyacetyloxy}-4-phenyl- 3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquinoline- 3(S)-carboxamide, and N-tert-buiyl-decahydro-2-[2(R)-{2-[3-(N,N-dimethylaminopropoxy)ethoxy]acetyloxy}-

4-phenyl-3(S)-[[N-(2-quinolylcarbonyl)-L-asparaginyl]amino]butyl]-(4aS,8aS)-isoquino- line-3(S)-carboxamide, or a pharmaceutically acceptable salt thereof. 16. A compound of formula I according to claim 1 wherein Rj is acetyl, or a pharmaceutically acceptable salt thereof. 17. A compound of formula I according to claim 1 wherein Rj is furan-2-ylcarbonyl, or a pharmaceutically acceptable salt thereof. 18. A compound of formula I according to claim 1 wherein Rj is methoxyacetyl, or a pharmaceutically acceptable salt thereof. 19. A compound of formula I according to claim 1 wherein Rj is pyridin-2-ylcarbonyl, or a pharmaceutically acceptable salt thereof. 20. A pharmaceutical composition comprising a compound of formula I according to any one of claims 1 to 19 or a pharmaceutically acceptable salt of such a compound , least one salt-forming group together with a pharmaceutically acceptable carrie^^ ' * ■ ^ 21. A pharmaceutical composition suitable for administration to a non-humanH o Yv 25 0 0 1 7 -109- warm-blooded animal for the treatment of retroviral diseases, comprising an antiretrovirally effective amount of a compound of formula I or of a pharmaceutically acceptable salt thereof according to claim 1 and a pharmaceutically acceptable carrier. 22. A method of inhibiting retroviral aspartate proteases in a non-human warm-blooded animal, comprising the administration of an antiretrovirally effective amount of a compound of formula I or of a pharmaceutically acceptable salt thereof according to claim 1 in combination with one or more pharmaceutically acceptable carriers to a non-human warm-blooded animal requiring such treatment. 23. A method of treating retroviral diseases in non-human warm-blooded animals, comprising the administration of an antiretrovirally effective amount of a compound of formula I or of a pharmaceutically acceptable salt thereof according to claim 1 or of a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1 in combination with one or more carriers to a non-human warm-blooded animal requiring such treatment. 24. A method of inhibiting the action of the enzyme retroviral aspartate protease in a non-human warm-blooded animai, comprising the administration of an effective amount of a compound of formula I or of a pharmaceutically acceptable salt thereof according to any one of claims 1 to 19 to said warm-blooded animal. 25. The use of any one of the compounds of formula I as claimed in any one of claims 1 to 19 or of a pharmaceutically acceptable salt of such a compound having at least one salt-forming group in the treatment of retroviral diseases in a non-human warm-blooded animal. 26. A pharmaceutical composition suitable for administration to a warm-blooded animal for the treatment or prevention of a retroviral disease responsive to the inhibition of retroviral aspartate proteases, comprising an antiretrovirally effective amount of a compound of formula I according to any one of claims 1 to 19, or of a salt thereof where salt-forming groups are present, and a pharmaceutically acceptable carrier. 27. A process for the preparation of a compound of formula I according to salt of such a compound, which comprises £50017 -110- a) reacting a compound of formula II (II) with a carboxylic acid of formula III RrOH CM), wherein Rj is as defined in claim. 1, or with a reactive derivative thereof, free functional groups in the starting materials of formulae II and III that are not intended to participate in the reaction being if necessary in protected form, and removing any protecting groups present, or b) amidating an amino compound of formula IV H (IV) wherein Rj is as defined in claim 1, or a reactive derivative thereof, with a carboxy! 25 0 0 17 -111- of formula V or with a reactive acid derivative thereof, free functional groups in the starting materials of formulae IV and V that are not intended to participate in the reaction being if necessary in protected form, and removing any protecting groups present, or c) amidating an amino compound of formula VI wherein Rj is as defined in claim 1, or a reactive derivative thereof, with a carboxylic acid of formula VII 2500 1 7 -112- nh2 (VII) OH or with a reactive acid derivative thereof, free functional groups in the starting materials of formulae VI and VII that are not intended to participate in the reaction being if necessary in protected form, and removing any protecting groups present, and, if desired, converting a compound of fonnula I obtainable in accordance with the above process having at least one salt-forming group into its salt and/or converting an obtainable salt into the free compound or into a different salt and/or separating any isomeric mixtures of compounds of fonnula I that are obtainable and/or converting a compound of formula I according to the invention into a different compound of formula I according to the invention. BALDWIN, SON & CAREY </div>