IL38643A - 5-phenyl(or pyridyl)-1h-3-hydroxy-1,5-benzodiazepine-2,4-dione derivatives,their preparation and pharmaceutical compositions containing them - Google Patents

Abstract

1374529 Benzodiazepines BOEHRINGER INGELHEIM GmbH 26 Jan 1972 [27 Jan 1971] 3719/72 Heading C2C Compounds of the general formula (R<SP>1</SP>=H, alkyl, alkenyl, hydroxyalkyl, cycloalkylalkyl; R 2 =unsubstituted or substituted Ph or Py; R 3 = halogen, CF 3 , NO 2 ) are prepared by (a) reducing a compound of the formula (b) mild oxidation of a compound of the formula (R 4 , R 5 =H, alkyl), or (c) reacting a compound of the formula (R 1 not H) with water, optionally followed in the case of (a) and (b) by introduction of a 1- substituent. The above compounds are tranquilizers and anti-convulsants, and may be administered in the form of pharmaceutical preparations containing them in association with a carrier. [GB1374529A]

Claims (1)

1. 38643/2 1. Compounds of the general formula: wherein represents a hydrogen atom; a straight or branched alkyl group with 1 to 4 carbon atoms optionally substituted in the CJ position by a hydroxy group; or an allyl; represents a phenyl group which may if desired be substituted by a halogen atom or by a trifluoromethyl or nitro group; or a pyridyl group; and represents a fluorine, chlorine or bromine atom or a trifluoromethyl or nitro group. 38643/2 2. 1 Compounds as claimed in claim j 1 wherein represents a hydrogen atom or a me hyl or ethyl group; 1*2 represents a phenyl group which may if desired be substituted in the o-position by a tri- fluoromethyl group; or a pyridyl group and represents a chlorine or bromine atom or a trifluoromethyl group. 3, ; 3-Hydroxy-l-methyl-5-phenyl-7-chloro-lH-l , 5- benzodiazepine-2 ,4-(3H , 5H)rdione. 4. ' ' 3-Hydroxy-5-(o-trifluoromethylphenyl)-7-chloro- lH-1 ,5-benzodiazepine-2 ,4-(3H, 5H)-dione. 5. 7-Chloro-3-hydroxy-l-methyl-5-(o-trifluoromethyl- phenyl) -lH-1 , 5-benzodiazepine-2 ,4-(3H ,5H)-dione. 6. 7-Bromo-3-hydroxy-l-methyl-5-(a-pyridyl)-lH-l , 5- benzodiazepine-2 ,4-(3H , 5H)-dione. 7. Compounds as claimed in claim 1, other than as — ■' ' ¾ claimed in any of claims 3 to 6 , as herein specifically disclosed. 8. ' A process for the preparation of compounds as claimed in claim 1 which comprises reducing a compound of the formula 38643/2 (wherein R. , R. and R- are as defined in claim 1) or a 1 ' 2 3 I 1 hydrate thereof whereby a compound of formula I (as defined in claim 1) is obtained. I 9." A process as claimed in .claim 8 wherein the reduction is effected by the use of zinc/glacial acetic acid or tin/hydrochloric acid. 20. A process as claimed in claim 8 or claims 9 wherein the reduction is effected at an elevated temperature. .11· A process as claimed .in claim 8 wherein the reduction is effected catalytically or by the use of' an alkali metal borohydride. ^12.; A process as claimed in claim, 11 wherein the alkali metal borohyU > *i >Ie comprises sodium borohydride. 13. A process for the preparation of compounds as ···'■':..; claimed in claim 1 which comprises the mild oxidation of a compound of the formula: 38643/2 « "L (wherein R^, and are as defined in claim 1 and R^ and R,. which may be the same or different each : represent a hydrogen atom or a straight or branched alkyl group). ' 14. ! A process as claimed in claim 13 wherein a' compound of formula III is used in which ^ and/or j I R_ represents a straight or branched alkyl group with | 1 to 4 carbon atoms. 15· : A process as claimed in claim! 13 or claimj 14J wherein the mild oxidation is !effected by the use„of ! potassium permanganate or chromic acid. 16.1 A process as claimed in any of claimsj 13; to 14 i wherein the mild oxidation is effected at a low temperature. 17.j A process as claimed in any of claimsj 13- 1 toj 16 ' wherein the mild oxidation is effected in a weakly acidic medium. , iQe I' A process for the preparation of compounds as claimed in claim 1 (wherein R^ is other than hydrogen) 38643/3 which comprises reacting a compound of the formula: (wherein R^, and R^ are as defined in claim 1 with the proviso that R^ is other than hydrogen) to convert the compound of formula IV into a compound of formula ! I. I I 19, ί A process as claimed in claimj 18 ' wherein the reaction is effected by the use of water, 20» J A process as claimed in claim le or claim! 19 wherein the reaction is effected in the presence of an inert solvent, 21, Ί A process as claimed in any of claims, 18 to^' 20 wherein the reaction is effected in the presence of copper powder or a copper salt. 22. A process as claimed in claimj 21 wherein the copper salt is copper sulphate. 23.i A process for the preparation of compounds as claimed in claim 1 (wherein R^ is other than hydrogen) which comprises reacting a compound of the formula: 38643/5- H an appropriate alkylating or allylating agent whereby a compound of formula I as defined in claim 1 (wherein is other than hydrogen) is obtained. 24. A process as claimed in claim 23 wherein the alkylating, or allylating agent comprises an alkyl or allyl halide or a dialkyl or diallyl sulfate. 25. A modification of a process as claimed in claim 23 or claim 24 wherein an alkali metal salt of the compound of formula la (as defined in claim 23) is i . used in place of the compound of formula la (as defined in claim 23 ) . 26. A process for the preparation of compounds as claimed in claim l(wherein represents a hydroxy- alkyl group) which comprises reacting a compound of the formula 2 (wherein and are as defined in claim 1) with an alkylene oxide). ■ ; i , 27.1 A process as claimed in claim 26 wherein the I . reaction is effected in the presence of a strong base. Ί 1 _ ·_:_. : ' 28. A process as claimed in claimi26 or claimi27 Ί ; ' · '· ;■ wherein the reaction is effected in the presence of i i ■ : i an appropriate solvent or mixture of solvents. j 29. A process as claimed in any of claims 26 to 28 ,! wherein the solvent comprises an alcohol, tetrahydrofuran, i ■ ■· ,. or dimethylformamide. j j " 'Ί ,.. .. , .. . j ;30.j A process as claimed in any of claims|26 | o \ 291 | wherein the reaction is effected in the presence of water. 131 J A process for the preparation of compounds as claimed in cl alkyl group) of formula: 38643/3 (wherein anc* ^-3 are as def ned in claim 1) with haloalcohol with 1 to 4 carbon atoms. 32 j A process as claimed in claim, 31 wherein the reaction is effected in the presence of a weak inorganic or organic base. 33 . A process as claimed in claim 31 or claim 32 wherein the reaction is effected at an elevated temperature. 34. A process as claimed in any of claims 31 to 33 wherein the reaction is effected in the presence of an organic solvent. 35 . A process as claimed in claim 34 wherein the solvent comprises a lower or higher alcohol. 36 . A process as claimed in a'ny of claims 8 to 35 substantially as herein described. 37. A process for the preparation of compounds as claimed in claim 1, substantially as herein described in any of Examples 1 to ;26. 38. Compounds as claimed in claim 1 when prepared by a process as claimed in any of claims 8 to : 37. 39. Pharmaceutical compositions comprising as active ingredient at least one compound of formula I as claimed in any of claims 1 to 6 and 35 in association with a pharmaceutical carrier or excipient.