Cyclohexylphenylessigsaeuren und Verfahren zu ihrer Herstellung

摘要

The invention comprises: (1) compounds of the general formulae and wherein R** represents a C1- 5 alkyl radical, R00 represents a methylene or ethylidene radical, Rp represents a cyclohexyl, cyclopentyl or C1- 5 alkyl radical, Rm represents a halogen atom or a C1- 5 alkoxy, trihalomethyl, C1- 5 alkylthio, SH,NH2, di-(C1- 5 alkyl)-amino, CN, NO2, CONH2, C1- 6 alkanoylamino, C1- 4 alkylsulphonyl, di-(C1- 5 alkyl)-sulphamoyl or OH radical, and x is 1 or 2, with the provisos that at least one Rm substituent is in one of the m-positions relative to the side chain, and that there is at most one trihalomethyl substituent which must be in such m-position; (2) non-toxic salts (e.g. NH4, alkali and alkaline-earth metal, Mg, Al, Fe and amine salts) and C1- 5 alkenyl and alkynyl, C3- 6 cycloalkyl, phenyl, (C1- 6 alkanoylamino)-phenyl, carboxyphenyl, carboxamidophenyl, C1- 5 polyhydroxyalkyl, phenyl-C1- 5 alkyl, mono- or poly-(C1- 5 alkoxy)-C1- 5 alkyl, di-(C1- 5 alkyl)-amino-C1- 5 alkyl, C3- 6 cycloalkylamino-C1- 5 alkyl and C3- 6 cycloalkoxy-C1- 5 alkyl esters of the acids of (1); (3) the preparation of compounds (A) by (a) reduction of the corresponding a -hydroxy derivatives (obtainable by hydrolysing the corresponding dl-nitriles to the amides, hydrolysing these to the acids and, if desired, resolving them to obtain the d-form); or (b) (when R**= Me or Et) reduction of compounds (B); (4) the preparation of compounds (B) by acid-catalysed dehydration of the corresponding a -hydroxyacids, obtainable as in (3) (a); (5) the resolution of the dl-acids (A) to obtain the d-isomers; (6) the conversion of the acids of (1) to salts by reaction with a base containing a pharmaceutically acceptable anion; (7) the conversion of the acids of (1) to the esters of (2) by reacting them or their salts with appropriate hydroxy compounds or halides thereof. Various interconversions of Rm substituents are also described. Starting materials.-The preparation of compounds of the general formulae (R being Me or Et) is described and exemplified. Also described in detail is the preparation of 2,3-dichlorophenylcyclohexane and its 4-nitro derivative, 1-(o-trifluoromethylphenyl)-cyclohexanol, o-(1-cyclohexenyl) and o-cyclohexylbenzotrifluoride, 5-nitro- and 5-amino-2-cyclohexylbenzotrifluoride, 4-cyclohexyl-5-trifluoromethylbenzonitrile, 4 - bromo - 2,6 - dichlorobiphenyl, 4 - cyclohexyl - 3,5 - dichlorobromobenzene, and methyl-(4-cyclohexyl-3,5-dichlorophenyl)-carbinol. Pharmaceutical compositions, having antiinflammatory activity, contain the compounds of (1) and (2) above as active ingredients.