NEW PHENYL IMIDAZOLYL ALKENYL DERIVATING

摘要

1354909 Phenyl-imidazolyl-alkenyl derivatives BAYER AG 20 Aug 1971 [22 Aug 1970] 39196/71 Heading C2C Novel compounds of the Formula I wherein R1, R2 and R3, which may be the same or different, are each a hydrogen atom or an alkyl radical; R4 is a hydrogen atom, an optionally substituted alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, or aralkynyl, aliphatic acyl, aromatic acyl, a group -R4#1-O-R4#11 (where R4#1 and R4#11 are saturated or unsaturated aliphatic hydrocarbon groups) alkyl-, alkenyl-, or alkynyl-sulphonyl or arylsulphonyl radical, or a radical of the general Formula (2) in which Y is an oxygen or sulphur atom and R12 is an optionally substituted alkoxy, alkenyloxy, alkynyloxy, alkylmercapto, alkenylmercapto, alkynylmercapto, mono(alkyl, alkenyl or alkynyl)amino or di(alkyl, alkenyl or alkynyl)- amino, optionally substituted aryloxy, optionally substituted arylmercapto, optionally substituted monoarylamino, or optionally substituted diarylamino radical, or an optionally substituted -NHSO 2 - aryl radical or an -N(alkyl)-CO-NH alkyl radical, or an amino or styryl radical); R5 is a hydrogen atom or an alkyl, alkenyl or alkynyl radical or an optionally substituted aryl radical; R6 and R7, which may be the same or different, are each a hydrogen atom or an optionally substituted alkyl, alkenyl, alkynyl, or aryl radical; R8, R9 and R10, which may be the same or different, are each a hydrogen atom or an alkyl, alkenyl, alkynyl, alkoxy or alkylthio radical or an electronegative group; X is an oxygen or sulphur atom or an -SO-, -SO 2 -, -NH-, or >N-R11 group (R11 being a straight- or branched-chain alkyl, alkenyl or alkynyl radical), provided that X cannot be a sulphur atom or an -SO- or -SO 2 - radical when R4 is an aliphatic acyl, aromatic acyl or alkyl-, alkenyl- or aryl-sulphonyl radical, and that X cannot be -SO- or -SO 2 - when R4 is a radical of Formula (2); m is an integer from 1 to 6; and n is 0 or 1; provided that m + n is never 0; and salts thereof may be prepared by (a) for compounds in which n is 1 and X is oxygen or NH, and R4 is acyl or sulphonyl or a group of Formula (2) reacting a compound wherein Z is OH or NH 2 with an acylating or sulphonylating agent; (b) reacting an alcohol of the formula with a compound of the formula (c) for compounds in which X is SO 2 , oxidation of a compound (d) for compounds in which n is 1 and X is oxygen or -NH- and R4 is hydrogen, reducing a compound wherein A is -CN or -COOR7#1 (R7#1 has the same meaning as R7); (e) for compounds in which n is zero, X is oxygen and R4 is hydrogen, reducing a compound of the previous formula wherein A represents -COR7#1 (R7#1 has the same meaning as R7). The intermediate diphenyl imidazolylacetic acid methyl ester may be prepared by reaction of imidazole with diphenyl chloroacetic acid methyl ester, which is in turn formed from its acid chloride and methanol. The intermediate 5-(p-chlorophenyl)-1,1-diphenyl-mercaptoethanol-1 may be prepared by reaction of 4-chlorothiophenol and α-chloro acetophenone to yield phenyl-4-chlorophenylthiomethyl ketone which is reacted with phenyl magnesium bromide. The intermediate diphenyl-imidazolylacetonitrile may be prepared by dehydration of diphenyl - α - chloroacetic acid amide to yield diphenyl - α - chloroacetonitrile which is reacted with imidazole. Pharmaceutical compositions of the compounds I show activity against fungi, bacteria and protozoa when administered parenterally, orally or topically alone or with the usual excipients.