CA2052894A1 - Use of substituted 2-mercaptonicotinic acid derivatives for combating endoparasites, new substituted 2-mercaptonicotinic acid derivatives and processes for their preparation - Google Patents

Abstract

Use of substituted 2-mercaptonicotinic acid derivatives for combating endoparasites, new substituted 2-mercaptonicotinic acid derivatives and processes for their preparation Abstract The present invention relates to the use of compounds of the general formula I

I

in which R1 represents C1-C8-alkyl, aralkyl, aryl or hetero-aryl radicals which are optionally substituted by halogen, cyano, nitro, amino, alkylamino, amino-acyl, alkyl, aralkyl, halogenoalkyl, alkoxy, aryloxy, halogenoalkoxy, alkylthio, arylthio, alkylsulphinyl, arylsulphinyl, arylsulphonyl, halogenoalkylthio, haloganoalkylsulphinyl, halogenoalkylsulphonyl or carbonylaryl, X represents O, or / N-R3, R2 represents C1-5-alkyl, aralkyl, alkenyl or alkinyl, R3 represents H or alkyl or R1 and R3, together with the adjacent N atom, represent a 5 or 6-membered heterocycle which can contain O or N as addi-tional heteroatoms and is optionally substituted by C1-4-alkyl, Le A 27 948-R4 represents hydrogen, halogen, alkyl, halogeno-alkyl, cyano, nitro, amino, aminoacyl, phenyl, alkoxy, aryloxy, thioalkyl and arylthio which are optionally substituted, for combating endoparasites in medicine and veterin-ary medicine.

Le A 27 9413

Description

~ 3 ~J ~ ~J i-~

The present invention relate~ to the ~se of substituted 2-merc~ptonicotinic acid derivatives for combating endoparasites, to new 2-mercaptonicotinic acid deriva-tives and to proc2s~e~ ~or their preparation.

Substituted 2-mercaptonicotinic acid derivativeq are already known. However, nothing i~ known about their use against endoparasites (Eur. J. Med. Chem. - ChLm. Thar.
20(1985) pp. 61-6~

1. ThP use of compounds of the general formula I

~_XE?
R4 ~ R2 in which represent~ C~-C~ alkyl~ aralkyl, aryl vr heteroa~yl radicals whi~h are optionally ~ubstituted by halo-gen, cyano, ni~ro, amino, aminoacyl, alkylamino, alkyl, aralkyl, halogenoalkyl, alkoxy, aryloxy, halogenoalkoxy, alkylthiol arylthio, alkylsulphinyl, a~ylsulph~nyl, arylYulphonyl, halogenoal~ylthio, halogenealkylsulphinyl, halo~enoalkylsulphonyl or carbonylaryl, X represents O, or ~ R3, Le A 27 948 - 1 -R2 represents Cl5alkyl, aralkyl, alkenyl or alkinyl, R3 repre~ents H or alkyl or Rl and R3, together with the ad~acent N atom, rQpxesent a 5 or 6-membered heterocycle which can contain O or ~ a~ additional heteroatoms and is optionally sub~tituted by ~l 4al~1, R4 represents hydrogen, halo~en, alkyl, halogenoalkyl, cyano, nitro, amino, ~mino~cyl~ phenyl, alkoxy, aryloxy, thioalkyl and arylthio whlch are optionally substituted, for combating endopara~ites in medicine nd veterinary medicine.

The compound~ of the formula I are known in some cases and can be prepared analogously to known processes.

2. New ~ubstituted 2-mercaptonicotinic acid derivatives of the general formula I

C -XRl R4 ~ sR2 in which Rl represents aryl or heteroaryl which are optionally sub~tituted by halogen, cyano, nitro~ a~ino, a~ino-e A 27 948 - ~ -2 ~ ~ 2 ~s ~: ~

acyl, alkylamino, alkyl, aralkyl, halo~enoal~yl, alkoxy, aryloxy, halogenoalkoxy, al~ylthio, aryl-thio, alkylQulphinyl, a~yl~ulphinyl, arylsulphonyl, halogenoalkylthio,halogsnoalkylsulphinyl,halogeno-al~ylsulphonyl or carbonylaryl, X represents 0 or the radical ~ -R3, R~ represents (C2-C5)alkyl, aralkyl, alkenyl or alkinyl, R3 represent~ H or alkyl or R1 and R3, ~ogether with the ad~ac~nt N atom, represent a 5 or 6-membered hetero-cycle which can contain O or N a~ addi~ional hetaro-atoms and i~ optionally substituted by Cl4al~yl, R4 repreaents hydrogen, halogen, alkyl, halogenoalkyl, nitro, amino, aminoacyl, ¢yano, alkoxy, axyloxy, thioalkyl, arylthio or phenyl which are optionally sub~tituted.

3. Process for the preparatlon of the compounds of ~he formula I
o R4 ~ R2 in which X, R1, R2 and R4 haue the meaning given under 2, Le A 27 948 - 3 -characterised in that a) compounds of the formula II

R4 ~ II

in which R2 and R4 have the abovementioned meaning and Y represen$s halogen, are reacted with compounds of the for~ula III
R1~X-H III
in which R1 and X ha~e the abovementioned meanings, or b) compounds of the formula Ia ~4 ~ XR Ia Le A 27 948 - 4 -. . .

2~f3i..~$~
in which Rl, R4 and ~ have the abovementioned meanings, are reacted with compounds of the formula TV

in which R2 haæ the abovementioned meaning but doe~ not xepresent hydrogen and A represents halo~en t or c) compound~ of the formula V

~- X - R 1 V

in which ~, Rl and R4 have the abovementioned meaning are reacted in the presence of a base with c~mpounds of the formula VI

Le A ?? 948 2 ~

Rl-S-H VI

in which Rl has the abovementioned meaning.

The compounds of the fonmula ~I) are outstandi~gly suitable ~or combating endoparasites, particularly in the field of veterinary medicine.

Preferred compounds of the formula I are ~:hose in which Rl represents C~4-alkyl, benzyl, cycloal~yl having up to 8-C atom~, phenyl, pyridinyl, pyrimidinyl, imid2zolyl, pyrazolylO thiophenyl, furanyl, thiazo-lyl, oxazolyl, benzothiazolyl and benzmidazolyl, which option~lly by one or more identical or dif-ferent radicals from the group comprising Cl~C4-alkyl, in par~icular methyl, C~-C4-alkoxy, in particular methoxy, ethoxy, methylenedioxy or ethylenedioxy, which are optionally sub~tituted by fluorine or ~hlorine, Cl-C4-halogenoalkoxy, in particular trifluoromethoxy or fluorochloroethoxy, Cl C4-hal~genoalkylthio~ in particular trif}uoro-methylthio or fluorochlor~m~thylthio, Cl-C4-alkyl-thio, in particular methylthio, halogenosulphonyl, in particular fluoro~ulphonyl, thiophenyl or chloro-sulphonyl, Cl~Cs-alkylsulphonyl, in particular methyl~ulphonyl, C~-C4-haloganoalkylsulphonyl, in Le A 27 948 - 6 -2~,?~

particular trifluorom~thyl~ulphonyl, C1-C~-halogeno-alkyl, in particular trifluoromethyl, halo~en, in particular fluorine or chlorine, NO2~ cyano, amino, Cl4alkylamino, Cl4-halogenoalkylamino acylamino in S particular acetylamino, phenylthio and pheno~y, which are optionally ~ub~tituted by one of the abovementioned radical~, X represents 0 or the radical ~ -R3, R2 represents Cl5-alkyl~ benzyl, ethylphenyl or C2 ~-alkenyl, R3 represents Cl5-alkyl or Rl and R3, together with the ad~acent N atom, represent a S- ox 6 membered saturatad heterocycle which can cont~in N or O as additional heteroatoms, 5 R4 repre~ent~ hydrogQn, halogen, al~yl or phenyl which i~ optionally substituted by one of the radicals mentioned ~or R~

Particularly preferred compound~ of the formula I
o Il -XR
R4 ~ ~2 are tho~e in which _e A 27 948 - 7 -2 ~ v~ '~r.

Rl ha~ the preferred meaning given further above, xepresents 0 or the xadical ~N-R3, ~2 repre~ents Cl5-alkyl or C26-alkenyl, R3 repreYen~s hydrogen, R4 repre ents hydro~en, halogen 8uch a~ fluorine or chlorine, or phenyl or C1~-alkyl.

Very par~icularly preferred compound~ of the formula I
are those in which Rl represent~ Cl~alkyl, cyclopropyl, cyclopentyl, cyclohexyl, benzyl, phenylethyl, propylphenyl, phenyl and pyridinyl which are ~ubstituted by hydrogen, halogen, in particular chlorine or fluor-ine, C~4-halogenoal~yl in particular trifluoro-me~hyl, C~4-halogenoalkyl, in par~icular SCF3, ~5 C~ 4 alkyl in particular methyl, Cl4-halogenoalkoxy in particular OCF3, phenoxy, carbalkoxy, cyano, nitro, C~-alkoxy, Cl4-alkylthio, C~4-al~ylsulphinyl or ~l-4-a~ sulphonyl ~

X represents 0 or the radical ~N-R3, ~ R2 repre~ents C~5-alkyl in particular Cl3-alkyl/ or C~6-alXenyl in particular alkyl, Le A 27 948 - 8 ~

r~ n ~

R3 represents hydrogen or Cl4 alkyl, R4 represents hydrogen, chlorine, methyl or phenyl.

The following compound~ of the formula I in whlch the radicals Rl, R2, R3 and X have the meaning given may be mentioned in particular:

~ R~

NH phenyl CH3 6-CH3 NH 4-Cl-phenyl n-C3H7 5-CN3 NH phenyl n-C3H7 6-CH3 NH phenyl n-C3~7 5-Cl NH 4-SCF3-phenyl CH3 6-CH3 NH 4-SCF3-phenyl n~C3~I7 5-Cl O phenyl CH3 H
Q phenyl n-C3H7 H
O phenyl n-C3H7 5-C1 O n-C4H~ n-C3H7 H
NH 4-C1-phenyl n-C3H7 5-Cl NH 4-Cl-phe~yl n-C3H7 6-phenyl NH phenyl n-C3H~ 6-phe~yl NH -CH~ C~3 )phenyl CH3 5-Cl NH -CH~CH3~naphthyl ~H3 5-Cl If 2-thioethyl-nicotinoyl ohloride iB employed as the L~ A 27 948 - 9 -2 ~ ~ 2 ~

compound of the ~ormula II and 4-trifluoromethylaniline is employed as the compound of the formula III in process (3a), the process can be represented by the following equation.
Ol O
C-Cl C-N~ ~ F3 L ~ F3~H -~ ~
~N~--SCH2CH3 '~ ~ SCH2CH3 S The compounds of the formula II are known in some case~.
They can be prepare~ by proce~ses known per se. For exampla Eur. J. Med. Chem.-Chim. ~her. 20, t1) 61-66 (1985).

Compounds of the formula II are preferably employed in which R2 and R4 ha~e tha preferred meanings given for the compounds of the formula I.

The following compounds of the formula II may be men-tioned in particular:

Le A 27 948 - lO -2 ~ ?c R4~5C - C 1 ~H3 H
~2Hs H
C3H7 }I
CH2-CH=CH~ ~
~H3 5 Cl C~H~ 5-Cl CH3 6-phenyl C3H7 6-(4-Cl-phenyl) C~H7 6-~4-CF3-phenyl) C2H5 6-(4 CH~-phQnyl) C3H, 5-Br CH3 5-Br ~he reaction i~ preferably carried out u~ing dil.uent~.

Suitable diluents in thi~ ca~e are virtually all the inert organic Aolvents. These preferably include ali-phatic and aromatic, optionally halogenated hydrocarbons~
benzine, ligroin, benzene, toluene, xylene, ~ethylena chloride, e~hylene chloride, chloroform, carbon tetra-chloride, chlorobenzene and o-dichlorobenzene, ether~
such as diethyl eth~r and dibutyl ether j glycol dimethyl Le A 27 948 ether and diglycol dimethyl ether, tetrahydrofuran and dioxane, k~ton2s ~uch a~ acetone, methyl ethyl ketone, methyl isopropyl ketone and methyl isobutyl ketone, esters such as methyl acetate and ethyl acetate, nitrile~
such a~ methyl a~etate and ethyl acetate~ nitriles such as, for example, acetonitrile and prcpionitrile dimethylacetamide and N-methyl-pyrrolidone and also dimethyl ~ulphoxide, tetramethylene ~ulphone and hexa-methylphosphoric triamide.

The reaction i~ carried out at ~emperature~ between +20C
and *18nC, preferably between 50C ~nd +90C.

The process i3 carried out by uni~ing approximately equimolar amount~ of the compounds of the formula II and III in one of the abovementioned diluents and heating.
After reaction i~ complete, the mixture i~ cooled and the precipitated solid iB ~iltared off, washed and dried.

Process (3a~ according to th~ invention i~ optionally carried out in the presence o~ a ba~ic reaction auxil-iary.

Tho3e which are suitable are all customary inorganic or organic base~, ~uch a~, for e~ample, alkali metal hydr-oxides~ alkali metal carbonata~, tertiary amine~ such as triethylamine, N,N-dimethylaniline, pyridine, N,N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclononene ~D8N) or diazabicycloundecene (DBU).
Tertiary a~ine~, such a~, for example, triethylamine, are Le A 27 948 - 12 ~

2 ~ 3 pr~fera~ly used.

If N-(4-trifluoromethylthiophenyl)-2-mercaptonicotinamide is employed a~ the compound of the fonmula Ia and ethyl iodide is employed as the compound of the formula IV in proces~ ~3b),the proce~s can be described by the ~ollowing general formula O o ~C-N~{~SCF3 CH ~CH2 I ~-N~SCF3 S~SH C H2CH3 The compounds o~ the formula IV are known and the preparation of the compound of the ormula Ia is described under (~c).

Compounds of the formula Ia are preferably employed in which R1 and R4 h~ve the particularly prefe~rred meaning~
given for the compounds of the formula I.

~he reaction i~ preferably carried out using diluents.

Suitable diluents for carrying out process (3a) according to the invention are preferably inert organic solvents.

In particular, these include aliphatic, alicyclic or aromatic, op~ionally halogena~ed hydrocarbons, such as, for example, benzine, ligxoin, benzene, toluene, xylene, L~ A 27 948 - 13 -2~32~ 3;
chlorobenzene, petroleum ether, pentana, hexane, heptane, cyclohexane, dichloromethane, chloroform, carbon tetra-chloride; ethers, such as diethyl ether, dioxane, tetra-hydrofuran or ethylene glycol dimethyl ether or ethylene S glycol diethyl ether; ketone~, such as acetone or buta-none; nitriles, ~uch as acetonitriles or propionitrile;
amides, ~uch a~ dLmethylfonmamide, dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethyl-phosphoric txiamide; e~ters, such a3 ethyl acetate or ba~e~, ~uch as pyridi~a.

Proces~ (3b) according to the invention i~ optionally carried out in the presence of a basic reaction auxil-iary.

Those which are suitabla are all customary inorganic or organic base~, such as, for example, ,alkali metal hydr-oxides, alkali metal carbonate~, tertiary amines, such as triethyl~mine, N,N-dimethylaniline, pyridine, N,N-dLmethylaminopyridine, diazabicyclooctane ~DA~CO), diazabicyclononene (D~3N) or diazabicyc:loundecer~e (DBU).
Alkali metal carbonate~, ~uch as, for ex~mple, sodium carbonate or potassium carbonate are preferably used.

The reaction temperatures can be varied within a substan-tial range when carrying out proce~ (3a) accor~ing to the invention. In general, the reaction is carried out at temperatures between +50~C and ~160C, preferably at temperature~ between ~60C and +9ODC.

Le A 2~ 948 - 14 -If N-(trifluorvmethylphenyl)-2-chloro 6-methylnicotin-amide is employed as the compound of the formula V and propyl mercaptan i9 employed as the compound of the formula VI in process (3c),the process can be described by the following equation ~ -N ~ F3 -C3H7SH ~ ~ F3 CH2C H~CH3 The compound~ Qf the formula VI are known, the compounds of the formula V are known or can be prepared by known proce~ses (German Published Specifications DO5 2,611,601, DOS ~,417,21S3.

The process is carried out by uniting approximately equLmolar amounts of the compound~ of the f.ormula (V) and (VI) in one o~ the given diluent~, optionally in the presence o a base, and heating. After reaction is complete, the mixture is cooled and the precipitated ~olid is filtered off, washed and dried.

Sol~ent~ used are ~hose mentioned a~ preferred for In addition, alcohols such as, for example, ethoxyethanol can preferably be employed. Ba~es used are those mentioned as preferred under proce~se~
Alkali metal hydro~ides are preferably employed.

Le A 27 948 - 15 -$ ~
The active compounds are suitable for combating p tho-genic endoparas it4 which are encountered in humans and in the keeping and raising of animal~ with productive, breeding, zoo; laborato~y, experimental and p~t anLmals, and have favourable toxicity to warm~blooded animals.
They are effective against all or individual 8tage8 of development of the pests and against resistant and normally sensitive strain~. ~y combating the pathogenic endoparasites disease, case of death and yield reduc-tion~ (for example in the production of meat, milk, wool,hide~, eggs, honey etc.~ ~hould be reduced so that more economical and ~impler keeping of animals i~ possible through the u~e o~ the active compound~. The pathogenic endoparasites include cestode~, trematodes~ nematodes and Acantocephalae, in particular:

From the order of the Pseudophyllidea, for 2xampl0:
Diphyllobothrium spp., Spirometra spp., Schi3tocephalu~
spp., Ligula ~pp., Bothridium 8pp., Diphlogonoporus spp..

From the order o~ the Cyclophyllidea, for example: ~eso~
cestoides ~pp., Anoplocephala 5pp., Paranoplocephala spp., M~nieazia ~pp~, Thy~ano~omsa spp., Thysanie~ia spp./ A~itellina 8pp., Stile~ia spp. J Cittotaenia spp., Andyra spp., Bertiella 8pp., Taenia 8pp., Echinococcus ~pp., Hydatigera Bpp., Davainea 8pp., Raillietina spp-, Hymenolepis 8pp., Eehinolepis spp., Echinocotyle spp-, Diorchis spp., Dipylidium spp.~ Joyeu~iella ~pp., Diplopylidium 8pp..

Le A 27 948 - 16 -~ ~ ~ 2 ~3 From the subcla3~ o f the Monogenea t for example Gyro-dactylus 8pp., Dactylogyrus 5pp., Polystoma spp..

From the subclas~ of the Digenea, for example:
Diplostomum Bpp., Posthodiplostom~m 8pp., Schi~tosoma spp., Trichobilharzia ~pp., Ornithobilharzia 8pp., Austrobilharzia 8pp., Gigantobllharzia 8pp., ~eucochloridium 8pp., Brachylaima 6pp., Echino~toma ~pp., Echinopar~phium 3pp., Echinochasmus ~pp.~ Hypoderae~m 8pp., Fasoiola ~pp., Fasiolide~ spp., Fasciolopsi~ spp., Cycloooelum ~pp., Typhlocoelum 8pp., Paramphi~tomum spp., Calicophoron 8pp-, Cotylophoron spp., Gigantocotyle ~pp., Fischoederius ~pp., Ga~trothylacus spp., Notocotylus spp., Catatropi~ ~pp., Plagiorchi~ ~pp., Pro~thogonimu~
spp., Dicrocoelium spp., ~urytrema spp., ~roglotrema spp., Paragonimus spp., Collyriclum spp., Nanophyetus spp., Opist~orchis spp., Clonorchi~ ~pp., Metorchis ~pp.
Heterophye~ 8pp ~, MetagonLmus spp..

From the order of the 2noplida, for example: ~richuris spp., Capillaria spp.~ Trichomosoides ~pp., Trichinella ~PP-Fro~ the order of the Rhabditia, for examples Nicronema spp., St~ongyloid~ spp..

From the order of the Strongylida, for example: Stronylus 8pp., ~riodontophoru8 8pp. ~ Oe~ophagodontu~ spp., Tæicho-nema ~pp., Gyalocephalu~ spp., Cylindrophar~nx 8pp.,Poteriostomum 8pp., Cyclococercus spp., Cylico6tephanu~

Le A 27 94~ - 17 -5pp., Oesophagostomum spp., Chabertia spp., Stephanurus spp., Ancylostoma spp., Uncinaria spp., Bunostomum spp., Globocephalus spp., Syngamus spp., Cyathostoma spp., Metastrongylus spp., Dictyocaulus ~pp~, Muellerius spp., protostrongylus ~pp., Neos$rongy1us spp., Cystocaulus spp., Pneumostrongylus spp., Spicocaulus ~pp., Elapho-strongylus spp. Parelaphostrongylus spp., Cxenosoma spp., Paracrenosoma spp., Angiostrongylus spp., Aeluro-strongylus spp., Filaroides spp., Parafilaroide6 spp., Trichostrongylus spp., Haemonchu~ 5pp., Ostertagia spp., Marshallagia spp., Cooperia spp., Nena~odiru~ spp., ~yostrongylu~ spp., Obeliscoides spp., Ami<lostomum 8pp., Ollulanus spp..

From the order of the Oxyurida, for example: Oxyuris spp., Enterobius spp., Passalurus spp., Syphacia spp., Aspiculuris 6pp., Heterakis spp..

From the oxder of the Ascaridia, fox example: Ascaris spp.l Toxascaris spp., Toxocara spp., Parilscaris spp., Anisakis spp., Ascaridia spp..

From the order of the Spirurida, for example: Gna~hos~oma spp., Physaloptera ~pp., Thelazia spp., Gongylonema spp., Habronema spp., Parabronema spp., Draschia spp., Dracun-culus spp.~

From the order of the Filariida, for example~ Stephano-filaria spp., Parafilaria 5pp., Setaria spp., Loa spp., Dirofilaria ~pp., Litomosoide~ spp., Brugia spp., Le A 27 948 - 18 -Wuchereria spp., Onchocerca spp..

From the order of the Gigantorhynchida, for example:
Filicollis spp., ~oniliformis spp~, Macracanthorhynchus spp., Prosthenorchis 9pp..

The productive and breeding animals include mammals such as, for example, cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer, reindeer, animals having valuable coats such as, for example, minkt chinchilla, racoons, birds such as, for example, hens, geese, turkeys, ducks, ~:resh and salt water fish such as, for example, trout, carp, eels, reptlles ~nd insects such as, for example, honey bees and silkworms.

The laboratory and experimental anLmals include mice, rats, guinea pigs, golden hams~ers, dogs and cats.

The pet animals include dogs and cats.

Administration can be carried out both prophylactically and therapeutically.

The administration of the active compounds i9 carried out directly or enteraLly, paren~erally, dermally or nasally in the form of suitable preparations by treating the environment or with the aid of moulded articles contain-ing acti~e compound such as, for e~ample, strips, sheets/
tapes, neckbands, ear tags, limb bands an~ marking Le A 27 -948 - 19 -~ ~ J 2 devices.

Enteral administration of the acti~e compounds i8 carxied out, for example, orally in the form of powders, tablets, capsules, pastes, drinks~ granules, 501ution8 which can S be administered orally, suspensions and emulsions, boli, medicated feed or drinking water. Dermal administration can be carried out, for example, in the form of dipping, spraying or po-tring~on and spot~ing-on. Parenteral administration i~ ~arried out, for example, in the form of the in~ection (intramuscular, subcutaneous, intra-venou~, intraperi~oneal) or by Lmplant~.
Suitable preparations are~

solutions suzh as in~ection solutions ~ oral solu~ions ~
concentrates for oral administration after dilution, 15 solutions ~or uQe on the skin ox ~n body cavitie~, pouring~on formulations and gels;

emulsions and ~uspension for oral or dermal administra-tion and also ~or in~ection; ~emi-solid preparations;

formulation~ in wh~ch the active compound i~ processed in an ointment ba~e or in an oil-in-water or water~in-oil emul~ion base;

solid preparation~ ssch as powders, premixes or concen-trate~, granules, pellets, tablets, boli, capsules;
aerosol~ and inhalant~, and moulded articles containing Le A 27 948 - 20 -.J i'.J
ac~ive compound.

Injection solutions are administered intravenously intramu~cularly and subcu aneously.

In~ec~ion ~olutions hxa prepsred by dis~olving the actiYe compound in a suitable solvent and, if nece~ary, adding additives such as solubilisers, acid~, base~, buffer salt~, antioxidants and preservatives. The solution~ are sterile filtered and bottled.

Solvents which may be mentioned are: physiologically tolerable solvents such as water, alcohols such as ethanol, butanol, benzyl alcohol, glycero}, propylens glycol, polyethylene glycols, N-methyl-pyrrolidone, and mixtures of ~he~e.

The active c~mpounds may optionally also be dissolved in physiologically ~olerable vegetable or synthetic oils which are ~uitable for injection.

Solubili~er~ which may be mentioned are~ solvents whi~h promote the solution of the active co~pound in the main solvent or prevent it5 precipitation. Examples are polyvinylpyrrolidone, polyoxyethylated cas~or oil nd polyoxyethylated sorbitan esters.

Preservatives ar~: benzyl alcohol, trichlorobutanol, p-hy~xoxybenzoic acid esteræ and n-butanol.

I.Q A 27 948 - 21 ~ 3 ~ 1 ~J ., ~
Oral solution~ are administered dirPctly. Concentrates are administered orally after previously diluting to the administration concentration. Oral solution~ and con centrates are prepared a~ described above for the in~ec-tion solution~ 9 it being pos~ible to di~pense with sterile working.

Solutions for use on the skin are poured on dropwlse, spread on, rubbed in, ~prinkled on or sprayed on. These solutions are prepared a~ described above for the in~ec-tion ~olution~.

It may be advantageous to add thickeners during ~hepreparation. Thickenex~ are- inorganic thickener~ such as bentonite~, colloidal silicic acid, aluminium mono~tear ate, org~nic thickeners such as cellulose derivative~, polyvinyl alcohol~ and their copolymers, acrylates and metacrylates.

Gels are applied to or spread on the s~in or introduced into body ca~itie~. Gel~ are prepared by adding such a quantity of thicken0r to solutions which have been prepared a~ described for tha in~ec~ion solution~ ~ha~ a clear composition ha~ing an ointmen~-like canBiStency rQsult~. The thickeners indicated further above are employed a~ thicken~rs.

Pouring-on ~ormulations ar~ poured onto or sprinkled onto li~ited areas of the ~kin, whereupon the active compound penetrate~ the ~kin and ~cts sy~temically.

2~_2~ - 22 -Pouring-on. formulations are prepared by di~solving, suspending or emul~ifying the active compound in ~uitable skin-compatibl2 solvent~ or 801vent mixtures. If appro-priate, further auxiliaries such a~ colorants, absorp-tion-promoting ~ubstances, antioxidank3, light screens and adhesives are added.

Solvent3 which may be mentioned are: water, alkanols, glycols, polyethylene ylycol~, polypropylene glycols, glycerol, aromatic alcohol~ such as benzyl alcohol, phenylethanol, phenoxyethanol, e~ters such as ethyl acetata, butyl acetata, benzyl benzoate, ethers such as alkylene glycol alkyl ethers such as dipropylene glycol monomethyl ether, diethylene glycol mono-butyl ether, ketones such as acetone, methyl ethyl ketone, aromatic and/or aliphatic hydrocarbon~, vegekable or ~ynthetic oils, DMF, dLmethylacetamide, N-methylpyrrolidone and 2~2-dimethyl-4-oxy-methylene-1~3-dioxolane.

Colorants are all colorants which may be dissol~ed or suspended and which are permitted for administration to 2û animals~

~bsorption-promoting subYtances are, for e~ample, DMS0~
spreading oils such a~ i~opropyl myristate, dipropylene glycol pelargonate, silicone oil~, fakty acid esters, triglycerides and ~atty alcohols.

25 ~ntioxidant~ are sulphites or metabisulphite~ such as pota~sium metabisulphite, ascorbic acid, butylhydroxy-_e A 27 948 - 23 -2~ J~

toluene, butylhydroxyanisole and tocopherol.

Light screen~ are, for example, novanti~olic acid.

Adhe~ives are, for example, cellulosa derivative~, starch derivativQs, polyacrylates, and natural polymers ~uch a~
alginates and gelatin.

Emul~ions may be administered orally, dermally or a~
in~ections~

Emul~ion~ are either of the water-in-oil t~e or tha oil-in-water type.

They are prepared by dissol~ing the active rompound either in the hydrophobic or the hydrophilic phase and homogenizing thi~ with th~ solvent of the othex pha~e with the aid of ~uitable emul~ifiar~ an~, if appropri~te, further auxiliaries such as colorant3, absorption-promot-ing sub~tances/ preservative~, an~ioxi.dants, lightscxeens and vi~co~ity-increasing substance~.

Hydrophobic phases (oils) which may be mentioned are:
paraffin oilst ilicone oils, natural vegetable oils ~uch as se~ame oil, almond oil, ca~tor oil, ~ynthetic trigly-cerides ~uch a~ caprylic/capric acid biglyceride ortriglyceride mixture wîth vegetable fatty acids of chain length C8-l2 or other specially sel~ctad natural fatty acids, partial glyc~ride mixture~ of ~aturated or unsaturated fatty acids possibly al80 containing hydroxyl Le A 27 948 - 24 -r;~

groups, and mono- and diglyceride~ of C6/CLO-fatty acids.

Fatty acid ester~ such as ethyl stearat~, di-n-butyryl a~ipate, hexyl lauroate, dipropylene glycol pelargonate, ester~ of a branched fatty acid of medium chain length 5 containing saturated fatty alcohol~ o chain length Cl~-Cl8, isopropyl myristatet isopropyl palmitate, cap-rylic/capric acld e~ters of ~aturated fatty alcohols o~
chain length Cl2-Cl~ opropyl stearate, oleyl oleate, decyl oleate, ethyl oleate, ethyl lactate, waxy fatty acid e~er~ such as ~ynthetic duck coccygeal gland fat, dibutyl phthalate, dii~opropyl a~ipate, ester mix~ures related to the latter etc.

Fatty alcohol~ ~uch as isotridecyl alcohol, 2-octyl-dodecanol, cetylstearyl alcohol and oleyl alcohol.

Fatty aclds ~uch as, for example, oleic acid and its mixtures.

Hydrophilic phases which may be mentioned are:
water, aloohols such as, for example, propylene glycol, glycerol, sorbitol and their mixtures.

Emulsifier~ whioh may be mentioned are~ non-ionic surfac-tants, for ~xample polyoxyethylated ca~tor oil, polyoxy-ethylated sorbitan monoolea Q ~ sorbitan monostearate, qlycerol mono tearate~ polyoxyethyl ~tearate and alkyl-phenol polyglycol ether;

Le A 27 948 - 25 -2~ ~ D 7 ,~ 7 a~pholytic surfactant~ ~uch as di Na N-lauryl~ mino-dipropionate or lecithin;

anionic surfactant~, such as Na lauryl ~ulphate, fatty alcohol ether ~ulphate~, mono/dial]~yl polyglycol ether orthophosphoric acid ester monoethanolamine salt;

cationic surfactant~ such a~ cetyltrimeth~lammonium chloride.

Other auxiliaries which may be mentione~ are: substances increasing vi~cosi~y and stabilising the e~ul~ion such a~
carboxymethylcellulo~e, methylcellulose and other cellu-lose and ~tarch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinylpyrrolidone, polyvi.nyl alcohol, copolymer o methylvinyl ether and maleic anhydride/ polyethylene glycols, waxe3, colloidal ~ a or mixtur~s of the ~ubsta~ce~ mentioned.

Suspensions may be administer~d orally, der~mally or a~ an in~ection. They are prepared by suspendi:ng the active c~mpound in an excipien~ liquid, if appropria~e with the addition o~ other auxiliaries ~uch a~ wetting agsnt~, colorant~, ab~orption-promot~ng sub~tances, presexva-tives, antioxida~ts light screens.

Excipient liguid3 which may be mentioned are all homo-geneou~ sol~ents and ~olvent mixtures.
Wetting agents (dispersant~) which may ba mentioned ar~

Le A 27 948 - 26 -2 ~

the surfactants indicated further above.

Other auxiliaries which may be mentioned are those indicated furthar above.

Semi-~olid preparation~ can be administered orally or dermally. They diffar from the suspensions and emulsLon~
de~cribed above only by their higher viscosity.

In order to prepare solid preparations~ the active eompound i8 mixed with suitable excipients, if approp-riate with th~ addition of auxiliari~, an~ brought lnto the de6ired form.

Excipientæ which may be mentioned are all physiologically tolerable solid inert substance~. Those used are inor-ganic and organic subs~ances. Inorganic substances are, for ex~mple, ~odium chloride, carbonate~ ~uch as calcium 1~ carbonate, hydrogen ~arbonates, aluminium oxides, 8ilicic acid~, aluminas, precipitated or colloid~ ilica and phosphate~.

Organic substan~e~ are, for example, ~ugars, cellulose, food~tu~f~ and feed3 ~uch as ~ilk pow~er, animal meal, cereal meal and ~hreds, and ~tarches.

Auxiliarie~ are pre~ervative~, antioxidant~ and colora.nts which ha~e alresdy been listed further above.

Other suitable auxiliarLe~ are lubricant~ and glidants Le A 27_948 - 27 -~ qi ~ 2 ~.3` ~

such a~, for example, magnesium ~tearate, stearic acid, talc, ~entonites, disintegration-promoting substances such a~ s~arch or crosslinked polyvillylpyrrolidone, binder~ such a~, for example, starch, gelatin or linear polyvinylpyrrolidone and dry ~inders ~uch as micro-crrstalline cellulo~e.

The active compound~ may al~o be presen~ in the prep ra-tions a~ a mixture with 8ynergi~t3 or with other active compounds wh~ch act agalnst patho~enic endopara~ite~.
Such ~ctive compounds are, for ex~mple, L-2,3,5,6-tetra-hydro-6-phenylimidazothiazole, benzimidazole carbamate, praziquantel, pyrantel and febantel.

Ready-to-use preparations contain ths acti~e compound in concen~rations of 10 ppm - 20 per cent by weight, prefer-ably from 0.1 - 10 per cent by weight.

Preparation~ which are diluted be~ora u~e contain the active compound in concentrations of 0.5 - 90 per cent by weight, preferably from 5 to 50 per cent ~y wei~ht.

In general, it has proved advantageou~ to administer amount~ of about 1 to about 100 mg o~ active compound per kg of body weight per day to attain effective results.

Ls,A 27 ~48 - 28 -Example A

In vivo nematode test Trichostrongylus colubriformis/~heep Sheep infected experLmentally with Tricho~trongylus colubriformis were treated after expiration of the prepatenoy period of the parasite. The active compounds were administered orally as pure active compound in gelatin capsules.

The degree of action is determined by quantitati~ely counting the worm eggs excreted with the faece~ before and after the treatment.

A complete stop to egg laying after the treatment means that the worms have been expelled or damaged such that : they no longer produce eggs (effecti~e dose).

Active compounds te~ted and effective do~-3s can be seen fr~m the following table.

Le A 27 948 - 29 -i2 ~ ~ 2 f~

Activa compoundEf fective dose in Example Na. mg/kg 13 lû

B7 lO

L~ A 27 .248 - 30 -2~ 3 Example B

In vivo nematode test Haemonchus contortusJsheep Sheep infected experLmentally with Ha~monchus contortus wsre treated after expiration of the prepatency period of the parasite. The active compounds were administered orally as pure aotive compound in gelatin capsules.

The degree of action i8 determined by quantitatively counting the worms excreted with the faeces before and a~ter the treatment.

A complete stop to egg laying after the treatmen~ means that ~he worm~ have been expelled or da~aged such that they no longer produce eggs (effective dose).

Active compounds tested and effective dos~.3s ca~ be seen from the followinq table.

L~ A 27 948 - 31 -Acti~e compoundEffective dose in Example No. mg/kg 1~

2~ 10 Le A 27 948 32 -Y ~
Preparation Examples [~S-C~ H2 ~ 3CF3 C~2CH3 CH2CH3 8.7 g ~43 mmol) of ethylmercaptonicotinoyl chloride are di~solved in 120 ml of dry Setrahydrofuran and 7.0 g (43 mmol) of 4-trifluoromethylaniline and 4.4 g of triethylamine di~solved in 50 ml of THF axe added. ~he mixture i9 stirred ~t reflux temperature for 3 h, allowed to cool and diluted with wa~er, and the precipi~ate which is deposited i8 filtered off with suction. After drying, 11.8 g t84%) of the N-phenyl-ethylmerc ptonicotinamide result.

C-Ul~ScF'3~, ~-N1~3S~F3 H2C~3 14~3 g t48 mmol) of N-phenyl-mercaptonicotinamide are dis~olv~d in 150 ml of dry methanol and 1.92 (48 mmol3 of ~aOH are added. ~he mixture i6 subse~uently stirred at RT
for ~O min and 7.1 g (56 mmol) of ethyl iodide in SO ml o~ methanol are then added dropwise. Tha mixture l~

iL~L~ 33 ~

~ 3 r~ ~t ~

subsequently stirred at room temperature for 1 h water is added and the solid which is d~posited is filt~red off with suction. 12.5 9 ~73%) of the ethylmercapto compound are obtained.
Example of process 3O

O O
-NH ~ F3 nPr~H ~ -NH ~ CF3 C:H2CH2CH3 1.9 ~ (25 ~mol) of n-propylmercaptan are dissolved in 100 ml of ethoxyethanol and 1.4 g (~5 mmol~ of KOH are added. 7.6 g ~25 mmol) of ~-phenyl-chloronicotinamide are added dropwise to this ~olution and the mixture i8 sub equently stirred at 80C for 2 h. Thi mixture i~
10 cooled ~nd water is a ded. The solid which i8 deposited i8 iltered off with ~uction. 6.6 g (77%) o N-phenyl-thiopropylnicotlnamide are thus obtained.

The following compounds can be prepared analogously to this proce~

Le A 27 948 - 34 -~_R2 Ex . X Rl R~ M. p .
No t CJ
NH PhQnyl CH3 164 2 NH Ph~nyl n-C3H7 121 3 NH Phenyl CH2-CH=CH2 137 4 NH 2-Cl-Ph~nyl CH3 102 NH 2-Cl-Phenyl CH2-CH-CH291 6 NH 2-Cl-Phenyl n-C ~H7 98 7 NH 4-C:l-Phanyl C~3 158 8 NH 4-Cl-Ph~nyl CH2-CH=CH2 138 9 NH 4~Cl-Ph~nyl n-C3H7 13û
NH 2-OCF3-Ph3nyl CH~ 120 11 NH 2-OCF3-Ph~nyl CH2-CH=CH2 100 ~2 N~ 3-CF3-Phenyl n-C:3H786 13 NH 4~ Phenyl C2H5 143 14 NH. 2-Cl-i~h~nyl G2H5 110 IS NH Phclrlyl C2~5 157 16 NH 4-CF3-Phq~Yl C2H5 154 17 N~ 4-SCF3-Phenyl C2~5 156 ~ 8 NH 2-OCF3~E'honyl C2H5 103 Le_A 27. 948 - 35 -2 ~ ~ ~J ~.';' .~ ~'.' Ex. X R1 R2 M-P-No. ~ C~
_ _. __ 19 NH 2-OCF3-Phanyl n~C3H790 2n Nll 4-SCF3-Phenyl n-G~H7121 21 NH Phenyl ~-C5H1191 22 NH 2-Cl-Ph~nyl ~--C5H118Z
23 N}l 4-Cl-Ph~nyl n ::5H1 130 24 NH Phsnyl C;~H5157 NH 4-CF3-Phenyl C2H5154 26 NH 4-SCF3-Ph-nyl C2H5156 27 NH 2-OCF3-Ph~nyl C2H5103 28 NH 2-OCF3-Ph~nyl n-C3H790 29 NH 4-SCF3-Ph~nyl n~C3H7121 NH Ph~nyl n-CsH1191 31 NH 2-C:l-Ph~r,yl n-CsH1182 32 NH 4-C1-Ph~nyl n-CSH11130 33 NH 2-O~:F3-~henyl n-CsH1180 34 NH 4-SCF3-Ph~nyl CH3 15~
NH 2-CH3-Ph~n~rl CH2-CH=CH2 114 36 NH 4-CH3-Phenyl CH2-CH=CH2 i2lB
3r N~l 2-CH3-PhQnyl C2H513'9 3B NH 2-CH3-Phenyl n~C3H7105 Le A 27 948 - 35 -2~3~

Ex. X R1 R~ M.p 39 NH 4-CH3-Ph~nyl C2H5 12 NH 4-CH3-~h~nyl n C3~7 127 41 NH ~y-C6Hll C2H5 128 42 NH 5Y-~6Hll n CSH11107 43 NH Cy-C~Hl1 CH3 169 ~4 NH 3-CI, 2-CH3-Ph~nyl n-C3H7 93 NH Cy-C6Hll n C3H7 lU2 46 NH 3-Cl, 2-CH3-Ph~nyl CH2-CH=CH2 63 47 NH Cy-C6~11 CH?-CH=CH2 122 48 NH 2-C~3-Ph~nyl ~2~5 93 4g NH 2-CH3-Ph~yl CH3 151 5~ NH 3-CF3-Ph~nyl CH~-CH=CH2 51 NH 3-C~3-Phsnyl CH3 121 52 NH 4-CH3-Ph~nyl CH3 176 53 NH 2-CH3, C1-PhGnyl CH3 12~
54 NH 2-CH3-Ph~nyl n CsH~l 120 5~ NH 4-CH3-PhQnyl n-C5H1174 56 NH 2-Cl, 3-CH3-Ph~nyl ~ CSHll 57 NH 3-C~3-Ph~nyl n-CsH11 5~ NH i-C3H7 CH3 134 59 NH i-C3H7 ~2~5 107 NH n-C4H9 C2~5 61 Le A 27 948 - 37 -2 ~ ~ 2 ~

E x ~ Rl R2 t'C i , .
61 NH t-C~aH9 C2H5 141 62 NH i C3~7 CH2-CH=CH292 S3 NH ~ C4~9 CH~-CH=CH247 64 NH ~ C5Hl 1 C2H5 52 NH i C3H7 n C3H7 82 66 NH n-C4~19 n-C~H7 49 67 NH t-C~Hg n^C3H7116 68 NH n-~5~59 n C3H7 69 NH t-C~aH9 c~3 131 NH n ~5H1 1 CH3 58 71 NH t C4H9 CH2-CH- CH2110 72 N~ rl CSHll CH2-CH=CH297 73 NH ~-C4H9 CH3 58 74 NH i-C3H7 ~:5H1 I62 N~ n C4H9 n-C4Hg 76 NH n CSH11 n-t 6~H9 77 NH i C8H7 n-C5H1 199 78 NH 4-F, 3-CI-PhQnyl C2HS15:3 79 NH 2,5-C1~3-Ph~rlyl C2HS 142 8n NH 2, 3-CH3-~h6ar~Yln~C3H7 126 81 N}S 3-Cl, J,-F-Ph~nyl s~-C~H7126 Le A 27 g48 - 38 -f'f,`;,'~

Ex. X Rl R2 M.p N o . t C

82 NH 3-OCH3-Ph~nyl CH~ 129 83 NH {~sCF'3 C~3 163 l3~ ~1 ~ ~3Cl C~3 121 NH ~1 CH3 156 86 NH 3-CH3-Ph~nyl CH3 125 87 NH ~S{~l CH3 132 P'3C
88 NH 3-Cl~Phonyl CH,I ~8 8~ NH 2-C}13-P~onyl CH3 ~ 04 9l~ 4-S:H 3-Ph~nyl CH3 101 ~1 NH 2-Cl-P21~nyl -C~2-~h~nyl 126 92 NH 2-OC:H3-Ph~nyl CH3 108 93 NH 4-OCH ~-Ph-nyl C~3 123 ~4 NH 4-CF3-Ph0nr~ CX3 96 ~ -CH2-Ph~nyl CH3 ~ ~L 2 g6 NH -CH ~ CH3 ~ -Ph~nyl C~i 109 Le A 27 948 - 39 Ex. X R1 R~ M.p.
No. t C~

97 NH ~ H~CH2)2-PhenY1 CH3 105 98 NH 3,4-C:l-Ph~nyl n-C ~H798 99 NH 2,~-Cl-P}l~nyl n C3H7113 100 Nl~ 2-CH3-Phonyl n-C3H7 10~
101 NH 2-Cl-Ph~nyl n-C3~7 133 102 NH 2-CH3-Ph~nyl n ~3~77'7 iO3 NH 3-t3CH3-Phenyl n ~3}~7 82 104 NH 4~ Ph~nyl n ~ 3~7 87 05 NH 2-F-Phenyl n C3H7102 106 NH 4-OCH3-Ph3nyl n-C3H7 95 lC17 NH 4-CH3-E'h~nyl n~C3H7103 108 N~l 4-C2H5-Ph~nyl n-C3H7 97 109 NCH Ph~nyl n-C3~7Oi l llO NH 3-Cl-Phonyl n C3~784 111 N~ 4-~iph~nyl n C3H7134 112 N~ 4 Cl-Ph~nyl n C3}~7 92 113 N~ l-NI~pht.hyl n C3H7141 1 14 NH 3,4-Ci-Ph~nyl C2H5 lC~5 l1S NH 2-CH3-Ph~nyl ~2H5 118 11~ NH 2-Cl-Phonyl C2~S 12f5 117 NH 3-C:~3-PA~nyl C2H5 96 Le A 27 948 - 40 -c,~ r j ~

Ex. X ~1 R2 M.p.
5 No, ~C~

118 NH 4-F-Phenyl CzH5 101 119 NH 4-OCH3-Phenyl C2H5 102 120 NH 4-CH3-Phenyl C2H5 g7 121 NH 3-Cl-Phenyl C~,H~ 95 122 NH -CH~CH3)-(4-Biphenyl) C2~5 139 123 NH -CHtCH3)-(4-Cl-Phenyl] C2H5 94 124 NH -CH(CH3)-t4-CzH5-Phenyl) C2H5 103 125 NH 4-NHCOCH3-Phenyl CH3 255 126 NH 4-NHCOCH3-Phenyl n-C3H7 212 127 NH 4-S02CH3-Phenyl n-C3H7 165 128 NH 4-SCH3-Phenyl n C3~7 126 129 NH 4-OCH3-Phenyl n~C3H7 112 1 3n NH 4-C02CH3-Phenyl n-C3H7 119 131 NH 4-F-Phenyl CH3 165 132 NH 4-C02CH3-Phenyl CH3 118 132 NH 4-Co2cH3-Pheny~ CH3 118 133 NH 4-CN-Phenyl n C3H7 103 134 NH 4-N02-Phenyl n C3H7 115 135 NH 4-CN-Phsnyl CH3 179 136 NH 4-N02-Phenyl CH3 143 137 NH 4-S02CH3-Phenyl CH3 121 138 NH 4-SCH3-Phenyl CH3 175 Le A 27 94~8 - 42 - ~ ~3.~ 9 .~

E~. X ~1 R2 M.p.
S No. r~C]

CN
139 NH ~ C ~ SCF~ CH3 175 Cl 140 NH 2-CH3, 3-Cl-Phenyl C~H5 92 141 NH -CH2-(2-Cl-Phenyl) C2H5 101 142 NH -CH2-t2-Cl-Phenyl) n-C3~7 99 143 NH -CH2-t2-Cl-Phenvl) n C5H1196 144 NH -CH2-(2-Cl-Phenvl) CH3 112 145 NH -CH2-tZ-Cl-Phenyl) CH2-CH=CH2 74 146 NH -CH2-CH(C2Hs)-n-c4H9 C2H5 Oil ~47 NH -CH2-CH~C2Hs)-n-c4H9 n C3~7Oil 148 NH 4-SCF~-Phenyl CH2-C`H=CH 92 14~ NH 4-SCF3-Phenyl n C5H1188 150 NH ~CH2-Phenyl n C3H7116 151 NH 2,4,6-Cl3-Phenyl n C3H7 62 152 NH 4-OCH3-Phenyl n C3H7127 153 N~ 2~6-C12-Phenyl n~~3H7Oil 154 NH -CH2 Phenyl CH3 122 155 NH -CH2-Phenyl n C5H1191 156 NH -CH2-Phenyl CzH5 122 157 NH 4-F-Phenyl n C3H7112 158 NH 4-OCH3-Phenyl C2H5 135 Le A 27 948 ~ ~ c~ J i'!

Ex. X R1 R2 M.p.
5 N~ ~C]
.
159 NH 2,4~6-C13-Phenyl CH3 182 160 NH 2~4~6-Cl3-Phenyl n CSH11 64 161 NH -CH2-Phenyl CH2-CH-CH2 117 162 NH 2,6-Cl2-Phenyl n-C5HllOil 163 NH 4-F-Phenyl C2H~ 99 164 NH 4-Cl, 2-F-Phenyl n C3H7 96 165 NH 3-Cl, 2-N02-Phenyl n C3H7109 166 NH 2,4-F2-Phenyl n~C3H7110 167 NH -CH(CH3)-Phenyl n C3~7109 168 NH 4-OCH3-Phenvl n C5H11111 169 NH 4-F-Phenyl CH3 168 170 NH 4-F-Phenyl CH2-CH~CH2 82 171 NH 2,4-F2-Phenyl CH2-CH=CH2 96 172 NH 4-F-Phenyl n-C5H11112 173 NH 2-Cl, 4-F-Phenyl C2H5 114 174 NH 3-Cl, 2-N02-Phenyl C2H5 112 175 NH 2,4-F2-Phenyl C2~5 113 176 NH -CH~CH3)-Phenyl ~2H5 98 177 NH 4-01, 2-F-Phenyl CH3 130 178 NH 3-Cl, 2-N02-Phenyl ~H3 211 179 NH 2,4-F2-Phenyl ~H3 105 ~5 Le A 27 948 - 44 ~ c, Ex. X ~1 R2 M~p.
5 No. ~C}
. . .. . . . _ . _ _ _ .
180 NH Pyrid-2-yl CH2-CH=CH2 96 181 NH 2-F~ 4-Cl-Phenyl CH2-CH~CH2 82 182 NH Pyrid-2-yl n-C5~11 Oil 183NH -CH(CH3)-Phenyl CH2-CH=CH2 106 184NH 2,4-F2-Phenyl n-C5H11 87 185NH -CHtCH~)-Phenyl n C5H11 106 186NH -(CH2)3 N ~ C2H5 Oil 187NH -(CH2)3-N ~ n C3H7Oil 188 NH(CH2)2~N~(3~4-Cl2-Phenyl C2H5 117 189 NH (CH2)2 ~-~3-4-Cl2-Phenyl n-C3H7 110 Cl 190NH ~CH3 C2Hs 87 N - N
191NH -(CH2)2-NtCH3)-PhenYl C2H5 75 lg2NH -ICH2)2-NICH3)-Phanyl n C3H7 69 193 C2H5 n C3H7 67 Le A 27 948 - 45 - ~ ~3 2 ,~

Ex. X R1 R2 M.p~
5 No. t~C]

195 CH3 n C3H7 115 1~7 CH3 CH2-CH=CH2 Oil 198 CH3 n-C5H11 Oil 19~ C2H5 n C5H11 Oil 201 C2H5 CH2-CH=c~2 202 0 Phenyl CH3 86 203 0 Phenyl CH2-CH=CH2 2~4 0 Phenyl n-C3H7 58 205 0 Phenyl n-C5H11 41 2Q6 0 4-CH3-Phenyl CH3 101 2a7 0 4-CH3-Phenyl CHz-CH=CH2 56 208 0 ~-CH3-Phenyl n~C3H7 3~
209 0 4-CH3-Phenyl n C5H11 Oil 210 0 4-OCH3-Phenyl n-C3H7 73 211 0 ~-OCH3- Phenyl CH3 lOQ
212 0 4-OCH3-Phenyl CH2-CH=CH2 85 213 0 4-Cl -Phenyl n C5H11 Oil 214 0 4-Cl-Phenyl CH2-CH=CH3 q2 215 0 4-Cl-Phenyl C2H5 69 Le A_27 948 - 46 ~ 2 3 e~ I

Ex. X Rl ~2 M.p.
5 No. rc~

216 0 2-CH3-Phenyl C2H5 Oil 217 0 4-CH3-Phenyl C2H5 66 218 0 i-C3H7 n C3H7 42 219 0 4-OCH3-Phenvl C2H5 4Z

~ X _ H3C ~ s_R2 220 WH 4-CH3-Phenyl CH3 159 221 NH 4-CH3-Phenyl ~2~5 155 222 NH 2-CH3-Ph~nyl CH~ 145 223 NH 2-CH~-Phenyl C2H5 111 224 NH 2-CH3-Phenyl i ~3H7 116 225 NH 2-CH3-Phenyl n-C3H7 99 Z26 NH 4-CH3-Phenyl n C3H7 129 227 NH 4-CH3-Phenyl i C3H7 113 228 NH Phenyl CH3 159 229 NH Phenyl C2H5 135 230 NH Phenyl n C3H7 153 231 NH Phenyl i-C3H7 119 232 NH 2-OCH3-Phenyl ~H3 94 Le A 27 948 ~ ~ J ~ r ~.~? ~, Ex. X R1 R2 M.p.
5 No. [~C~

233 NH 2-OCH3-Phenyl ~2~5 Oi1 234 NH 2-OCH~-Phenyl n C3~7 Oil 235 NH 2-OCH3-Ph~nyl i C3H7oi 1 236 NH ~,3-~CH3~2-PhenYl C~13 153 237 NH 2~3-~cH3)2-phenyl C2~5 146 238 NH 2,3-~CH3)2-Phenyl n C3H7 130 239 NH 2,3-~CH3)2-Phenvl i C3H7 126 240 NH 3,4-~CH3)2-PhenYl CH3 147 241 NH 3,4-~CH3)2-PhenY1 C2H5 127 242 NH 3,4-~CH3)2-Phenyl n C3H7 llZ
243 NH 3~4-(CH3)2-Phenyl i-C3H7 37 244 NH 4-OCH3-Phenyl CH3 156 245 NH 4-OCH3-Phenyl C2H5 143 246 NH 4-OCH3-Phenyl n C3H7 145 247 NH 4-OCH3-Phenyl i C3H7 147 248 NH 2-Cl-Phenyl CH3 129 249 NH 2-Cl-Phenyl C~H5 106 250 NH 2-Cl-Phsnyl n C3H7 87 251 NH 2-Cl~Phenyl i C3~7 72 252 NH 3-Cl-Phenyl CH3 157 ~5 - 48 - 2 ~

Ex. X R1 R2 M.p.
5 No. ~C~
_. . . .

253 NH 3-Cl-Phenyl C2~5 123 254 NH 3-Cl-Phenvl n C3H7 96 255 NH 3-C1-Phenyl i C3H7 Oil 256 NH 4-OCF3-Phenyl CH~ 162 257 NH 4-OCF3-Phenyl C2X5 143 258 NH 4-OCF3-Phenyl n-C~H7 116 259 NH 4-OCF3-Phenyl i C3H7 98 260 NH 4-SCF3-Phenyl CH3 168 2S1 NH 4-SCF3-Phenvl C2H5 152 2S2 NH 4-SCF3-Phenvl n C3H7 130 263 MH 4-SCF3-Phenvl i-C3H7 lZ3 264 NH 3,4-Clz-Phenyl C~3 159 265 NH 3,4-Cl2-Phenyl C2H5 100 Z66 NH 3~4-C12-Phenyl n~C3H7 103 Z67 NH 3~4-Cl2-Phenyl i-C3H7 108 268 NH 4-CF3-Phenyl CH3 lS1 269 NH 4-CF3-Phenyl C2H5 154 270 NH 4-CF~-Phenyl n C3H7 154 271 NH 4-CF3-Phenyl i C3H7 129 272 NH 4-Cl-Phenyl CH3 142 273 NH 4-C1-Phenyl C2H5 128 ~5 Le A 27 948 Ex. X R1 R2M.p.
5 No. ~C~
., . . ~
274 NH 4-Cl-Phenyl n C3H7 117 275 NH 2-C1~ 6-CH3-Phenyl n C3H7 99 276 NH 3.5-~CF3)2-PhenYl C~3145 277 NH 3~5-(CF3)2-Phenyl n C3H7 151 278 NH -CH2-Phenvl n C3H7 93 279 NH -CH-Phenyl n C3H7 81 280 NH -~H-Phenyl n C3H7 81 281 NH -CH2-CH2-PhenY1 n-C3H779 282 NH n C3H7 n~C3H7 63 283 NH i-C3~7 n~C3H7 85 284 NH i-C4H9 n C3H7 73 285 NH ~ C4H9 n-C3H755 286 NH Cy-C6H11 n C3H7 123 287 NH Cy-C~H9 n C3M7 85 288 NH Cy-C3H5 n C3H7 122 289 NH -CH-CY-C6Hll n~C3H7 116 290 NH -C-CY-C6Hll n C3H7 116 291 NH 2-CH3, 3-F-Phenyl n C3H7 110 292 NH 2-CH3, 3-F-Phanyl CH3164 Le A 27 948 - 50 - ~

Ex. X R1 ~2 ~,p 5 N~. ro~

293 NH 2-CH3. 3-Cl-Phenyl n C3H7 109 294 NH 2~3-Cl2-Phenyl n C3H7 103 o Cl ~ C-X-R
~S_~2 15 295 NH 4-Cl-Phenyl CH3 205 296 NH 4-CH3-Phenyl CH3 173 297 NH 4-cH3-phenyl C2H5 188 298 NH 4-CH3-Phenyl i C3H7 145 20 299 NH 4-CH3-Phenyl n-C~H~ 147 300 NH ~-OCH3 Phenyl CH3 154 301 NH 3-OCH3-Phenyl C2H5 129 302 NH 3-OCH3-Phenyl ;-C3H7 103 303 NH 3-OCH3-Phenyl n C4H9 125 304 NH 4-Cl-Phenyl C2H5 190 305 NH 4-Cl-Phenyl i C3H7 187 30 30~ NH 4-Cl-Phenyl n C4H9 146 307 NH 4-Cl-Phenyl n C3H7 16h 308 NH 4-Cl-Phenyl n C3H7 148 30~ NH 3-OCH3-Phenyl n C3H7 141 Le A ?7 948 5 1 ~ , V .', Ex, X R1 R2 M.p.
5 No. roc~
~ . ... _ _ _ .. .. _ _ . . . .
310 NH i C3H7 CH3 162 311 NH i C3~7 ~2H5 140 10 312 NH i C3~7 i C3H7 121 313 NH i C3H7 n-C~H9 140 314 NH i C3H7 n C3H7 12~
315 N -CH2-c!~-o-!cH-cH2 CH3 108 316 N -CH2-CIH-O-lH-~H2 C2H5 82 317 N -CH2-CH-0-CX-CH2- i C3H7 318 N -CH2-!H-0-!c~-c~2 n-C4H~ 43 319 N -CH2-CH-0-CH-CH2 n C3~l7 Oil 320 NH 3,4-C12-Phenyl CH3 188 321 NH 3~4-Cl2-Phenyl C2H5 161 322 NH 3~4-Cl2-Phenyl i C3H7 118 323 NH 3~4-C12-Phenyl n C4H9 145 324 NH 3.4-C12-Phenyl n C3H7 135 325 NH -CH2-Phenyl CH3 151 Le A 27 948 Ex. X R1 R2 m.o.
5 No. rc~
.
325 NH -CH2-Phenvl CH3 151 326 NH -CH2-Phenyl C2H5 142 327 NH -CH2-Phenyl i C3H7117 328 NH -CH2-Phenvl n-C4H~132 32~ NH -CH2-Phenyl n C3~7lS5 330 NH 4-F-Phenyl CH3 193 331 NH 4-F-Phenyl C2H5 178 332 NH 4-F-Phenyl i-C3H7161 333 NH 4-F-Phenyl n-C4H9146 334 NH 4-F-Phenyl n C3H,7155 3~5 NH 4-SCF3-Phenyl CH3 171 336 NH 4-SCF3-Phenyl C2H5 161 337 NH 4-SCF3-Phenyl i-C3H7123 338 NH 4-SCF3-Phenyl n~C4H9135 339 NH 4-SCF3-Phenyl n C3H7134 340 N -tCH2)2-!-tcH2)2 CH3 107 341 N -~CH2)z-y-~CH2)2- C2H5 73 342 N -(CH2)2-~-~CH2)2 i C3H787 Le A 27 948 Ex. X R1 RZ M.p.
5 N~. roc~

343 N -(CH2)2-y-(CH2~2 n-C4H9 73 344 N -(CH2)2-!N-(CH2)2 n C3H7 87 345 NH Phenyl CH3 188 346 NH Phenyl C2H5 180 347 NH Phenyl i-C3H7 124 348 NH Phenyl n-C4H9 130 349 NH Phenyl n~C3H7 142 350 NH 2-Cl-Phenyl CH3 174 351 NH 2-Cl-Phenyl C2H5 154 352 NH 2-Cl-Phenyl 1-C3H7 111 353 NH 2-Cl-Phenyl n-C4H9 138 354 NH 2-Cl-Phenyl n C3H7 125 355 MH 3-Cl-Phenyl CH3 162 35S NH 3-Cl-Phenyl C2H5 159 357 NH 3-Cl-Phenyl 1-C3H7 99 358 NH 3-Cl-Phenyl n~C4H9 100 359 NH 3-Cl-Phenyl n C3H7 120 360 NH 2-CH3-Phenyl CH3 184 ~5 Le A 27 948 Ex. X R1 R2 M.p.
5 No. rC]

361 NH 2-CH3-Phenyl C2H5 165 362 NH 2-CH3-Phenyl i-C3H7 139 363 NH 2-CH3-Phenyl n~C4H9 155 364 NH 2-CH3-Phenyl n~C3H7 154 365 NH 3-CH3-Phenvl CH3 179 366 NH 3-CH3-Phenvl C2H5 147 367 NH 3-CH3-Phenyl i C3H7 106 368 NH 3-CH3-Phenvl r-C4H9 118 369 NH 3-CH3-Phenvl n C3H7 140 370 NH -CH(CH3)-(4-CH3-Phenvl) CH3 154 371 NH -CH(CH3)-(4-CH3-Phenyl) C2H5 144 372 NH -CH(CH3)-(4-CH3-Phenvl) i-C3H7 132 ~73 NH -CH~CH3)-(4-CH3-Phenyl) n C4~9 149 374 NH -CH(CH3)-~4-CH3-Phenyl) n C3H7 133 377 NH CH3 i C3H7 81 378 NH CH3 n C4H9 100 379 NH CH3 n C3H7 119 380 N -tCH2)5- ~H3 78 381 N -(CHz)5- C2H5 74 Le A 27 948 ~2~'~J .~`~

Ex. X R1 R2 M.p.
5 No. [C]
. . . ~
382 N -tCH215- i C3H7 68 383 N (CH2)5- n C4H9 Oil 384 N -(CH2)5- n C3H7 Oil 385 N -(CH2)z~0-(CH2)2~ c~3115 386 N -(CH2)2-0-(CH2)2 C2H592 387 N -(CH2)2-0-(CH2)2 i-C3H778 388 N -(CH2)2-0-(CH2)2 n-C4H968 389 N -(CH2)2-0-(CH2)2 n-C3H752 3gO NH -CH(CH3)-P~enyl CH3 172 391 NH -CH(CH3)-Phenyl C2H5142 392 NH -CH(CH3)-Phenvl i-C3H7131 393 NH -CH(CH3)-Phenyl n C4~l9 124 394 NH -CH(CH3)-Phenyl n C3~l7 144 395 NH -(CH2)7-CH3 CH3 90 396 NH -~CH2~7~CH3 C2H592 397 NH -(CH2)7-CH3 i C3H7 71 398 NH -(CH2)7-CH3 n-C~H983 399 NH -(CH2)7-CH3 n C3H7 81 400 NH Cy C6H11 CH3195 401 NH Cy C6H11 C2H5178 Le A 27 948 56 ~ 3 ~3 Ex. X R1 R2 M.p.
5 No. rC]

402 NH Cy C6H11 i C3H7160 403 NH C~-C6H11 n C4H9142 404 NH Cy C6H11 n C3H7155 405 NH 2-OCH3-Phenyl CH3 122 406 NH 2-OCH3-Phenyl C2H5 94 407 Nff 2-OCH3-Phenyl i C3H7101 408 NH 2-OCH3-Phenyl n C4H997 409 NH 2~3-(CH3~2-Phenyl n C3~7105 410 NH 4-OCH3-Phenyl CH3 191 411 NH 4-OCH3-Phenyl C2H5 189 412 NH 4-OCH3-Phenyl 1 C3H7134 413 NH 4-OCH3- Ph enyl n-CgH9145 414 NH 4-OCH3-Phenyl n C3H7143 415 NH 4-OCF3-Phenyl CH3 171 416 NH 4-OCF3-Phenyl C2H5 160 417 NH 4-OCF3-Phenyl i C3H7113 418 NH 4-OCF3-Phenyl n C4~9134 419 NH 4-OCF~-Phenyl n~C3H7160 420 NH 4-CF3-Phenyl CH3 185 421 NH 4-CF3-Phenyl C2H5 202 422 NH 4-CF3-Ph~nyl i C3H7162 423 NH 4-CF3-Phenyl n C4H9150 Le A Z7 948 - 57 ~ t~

Ex. X Rl R2 M.p.
No~ ro C]

424 NH 4-CF3-Phenyl n C3H7 177 425 NH 2J4-C12-Phenyl CH3 181 426 NH 2~4-C12-Phenyl C2H5 145 427 NH 2~4-Cl2-Phenyl i C3H7 112 428 NH 2~4-C12-Phanyl n C4~l9 128 429 NH 2!4-Cl2-Phenyl n~C3H7 126 430 NH -CHtCH3)-~4-Cl-Phenyl) CH3 166 431 NH -CH~CH3~- ~4-Cl-Phenyl ) C2H5 143 432 NH -CH(CH3) - ~4-Cl-Phenyl ) i C3~7 144 433 NH -CH~CH3)-~4-Cl-Phenyl) n C4H9 13q 434 NH -CH~CH3) - (4-Cl-Phenyl ) n C3H7 126 435 0 Pheny l CH3 90 436 0 Pheny 1 C2ff5 91 437 0 Phenyl i-C3H7 88 438 0 Phenyl n-C4H9 48 439 0 Phenyl n C3H7 69 440 0 4-Cl-Phenyl CH3 112 :~o 441 0 4-Cl-Phenyl C2H5 122 442 0 4-Cl-Phenyl i-C3H7 77 443 0 4-Cl-Phenyl n-C4H9 61 444 0 4-Cl-Phenyl n-C3H7 70 ~5 Le A 27 948 - 5~ -S,, ~ ,S

Ex. X R1 R2 M.p.
5 No. ~C]

445 0 2-Cl-Ph~nyl CH3 106 446 0 2-Cl~Phenyl C2H5 121 lD 447 2-Cl-Phenyl i-C3H7 ~4 44a 0 2-Cl-Phenyl n-C~H9 79 449 0 2-Cl-Phenyl n-C3H7 98 450 0 3-CI-Phenyl CH3 132 15 451 0 3-Cl-Phenyl C2H5 123 452 0 3-Cl-Phenyl i C3H7 66 453 0 3-Cl-Phenvl n-C4H9 91 454 0 3-Cl-Phenyl n~C3H7109 455 0 4-OCH3-Phenyl CH3 95 ; 456 0 4-OCH3-Phenyl C2H5 ~3 457 0 4-ocH3-phenyl 1 C3~7Oil 458 0 4-OCH3-Phenyl n-C4H9 57 459 Q 4-OCH3-Phenyl n C3H7 65 Le A 27 948 - s~ -2~

~fC X-Rl ~<3_l;~U~S-~2 10 Ex. X ~1 R2 R3 M.p No.

460 NH 3-CI-Ph~nyl CH~ 4-C1 179 461 NH 3-Cl-Phenyl n~C3H7 H 139 462 NH Phenvl CH3 H 193 463 NH Phenyl n C3H7 H 200 464 NH 4-CH3-Phenyl CH3 H 2Z4 465 NH 4-CH3-Phenyl n~C3H7 H 204 : 466 NH 3-Cl-Phenyl CH3 H 143 467 NH 3-Cl-Phenyl n C3H7 4-C1 167 468 NH 4-OCH3-Phenyl CH3 H 223 469 NH 4-OCH3-Ph~nyl n~C3H7 H 201 470 NH -CH(CH3)-Phenyl CH3 H 198 471 NH -CHtCH3)-Phenyl n C3H7 H 198 . 472 NH 4-Cl-Phenyl n~C3H7 H 116 473 NH -(CH2~7-CH3 CH3 H 124 474 NH -tCH2)7-CH~ n~C3H7 H 114 475 NH 2~4-C12-Phanyl CH3 H 190 Le A 27 948 - 60 -- 2 ~ ~ 2 s Ex. X R1 R2 R3 M.p 5 N~. tC]

476 N -tCH2)2-0-(CH2)2- CH3 H 127 477 N -tCH2~2-0-~CH2)2 Il-c3H7 H 68 478 NH Cy-C6Hll CH3 H 205 479 NH Cy-C6Hll n~C3H7 H 178 480 NH 2,4-Cl2-Ph~nyl n~C3H7 H 105 482 N~ CH3 n C3~7 H 170 483 NH 4-OCH3-PhenylCH3 4-C1 263 484 NH 4-OCH3-Phenyln~C3H7 4-C1 207 48S NH -CH(CH3)-Phenyl CH3 4-Cl 486 NH -CHtCH3)-Phenyl n C3H7 4-Cl 151 487 NH -tCH2)7-CH3 CH3 4-Cl 125 488 NH -tCH2)3-CH3n~C3H7 4-Cl 116 489 NH 2~4-C12-Phenvl CH3 4-Cl 232 ; 490 NH 2,4-C12-Phenyl n~C3H7 4-Cl 182 491 N -(CH2)2-0-(CH2)2- CH3 4-C1 131 ; 492 N -tCH2)z~~~~C~2)2~ n~C3H7 4-Cl Oil ~0 493 NH Cy-C6~11 CH3 4-C1 205 494 NH Cy-C6Hll n~C3H7 4-Cl 230 495 NH CH3 CH~ 4-C1 205 496 NH CH3 n C3H7 `4-Cl 183 Le A 27 948 2 Q ~
Ex X Rl R2 R3 ~ ci 497 NH 3-Cl-Phenyl CH3 4-CH3 196 498 NH 3-Cl-Phenyl n~C3H7 4-CH3 162 499 NH 4-OCH3-Phenyl CH3 4-CH3 219 500 MH 4-OCH3-Phenyl n C3H7 4-CH3 191 SOl NH -CH(CH3)-Phenyl CH3 4-CH3 182 502 MH -CH~CH2)-Phenyl n~C3H7 4-CH3 149 503 MH n-C~H17enYl CH3 4-CH3 119 504 NH n-C8H17enYl n~C3H7 4-CH3 104 505 NH Cy-C6Hll n~C3H7 4-CH3 193 ~0 ~35 I,e A 27 9d.8

Claims (6)

1. Use of compounds of the general formula I

I

in which R1 represents C1-C8-alkyl, aralkyl, aryl or hetero-aryl radicals which are optionally substituted by halogen, cyano, nitro, amino, alkylamino, amino-acyl, alkyl, aralkyl, halogenoalkyl, alkoxy, aryloxy, halogenoalkoxy, alkylthio, arylthio, alkylsulphinyl, arylsulphinyl, arylsulphonyl, halogenoalkylthio, halogenoalkylsulphinyl, halogenoalkylsulphonyl or carbonylaryl, X represents O, or , R2 represents C1-5-alkyl, aralkyl, alkenyl or alkinyl, R3 represents H or alkyl or R1 and R3, together with the adjacent N atom, represent a 5 or 6-membered heterocycle which can contain O or N as addi-tional heteroatoms and is optionally substituted by C1-4-alkyl, Le A 27 948 R4 represents hydrogen, halogen, alkyl, halogeno-alkyl, cyano, nitro, amino, aminoacyl, phenyl, alkoxy, aryloxy, thioalkyl and arylthio which are optionally substituted, for combating endoparasites in medicine and veterin-ary medicine.

2. New substituted 2-mercaptonicotinic acid derivatives of the genaral formula I

I

in which R1 represents aryl or heteroaryl which are option-ally substituted by halogen, cyano, nitro, amino, alkylamino, aminoacyl, alkyl, aralkyl, halogeno-alkyl, alkoxy, aryloxy, halogenoalkoxy, alkyl-thio, arylthio, alkylsulphinyl, arylsulphinyl, arylsulphonyl, halogenoalkylthio, halogenoalkyl-sulphinyl, halogenoalkylsulphonyl or carbonyl-aryl, X represents O or the radical , R2 represents C2-C5-alkyl, aralkyl, alkenyl or alkinyl, Le A 27 948 - 63 -R3 represents H or alkyl or R1 and R3, together with the adjacent N atom, represent a 5 or 6-membered heterocycle which can contain O or N as addi-tional heteroatoms and is optionally substituted by C1-4-alkyl, R4 represents hydrogen, halogen, alkyl, halogeno-alkyl, nitro, amino, aminoacyl, cyano, alkoxy, aryloxy, thioalkyl, arylthio or phenyl which are optionally substituted.

3. Process for the preparation of the compounds of the formula I

I

in which X, R1, R2 and R4 have the meaning given in Claim 2, characterised in that a) compounds of the formula II

Le A 27 948 - 64 - II

in which R2 and R4 have the abovementioned meaning and Y represents halogen, are reacted with compounds of the formula III

in which R1 and X have the abovementioned meanings, or b) compounds of the formula Ia Ia in which R1, R4 and X have the abovementioned meanings, Le A 27 948 - 65 -are reacted with compounds of the formula IV

in which R2 has the abovementioned meaning but does not represent hydrogen and A represents halogen, or c) compounds of the formula V

V

in which X, R1 and R4 have the abovementioned meaning are reacted in the presence of a base with compounds of the formula VI

in which Le A 27 948 R1 has the abovementioned meaning.

4. Endoparasiticidal agents, characterised in that they contain at least one substituted 2-mercaptonicotinic acid derivative of the formula (I) according to Claim 1.

5. Process for the production of endoparasiticidal agents, characterised in that substituted 2-mer-captonicotinic acid derivatives of the formula (I) according to Claim 1 are mixed with extenders and/or surface-active agents.

6. Use of substituted 2-mercaptonicotinic acid deriva-tives of the formula (I) according to Claim 1 for the production of endoparasiticidal agents.

Le A 27 948 - 67 -