Patent GB-1354909-A (GB)
Title: Phenyl imidazolyl alkanyl derivatives their production and their pharmaceutical use
IPC: A61P31/04
Filed: 1971-08-20
Abstract: 1354909 Phenyl-imidazolyl-alkenyl derivatives BAYER AG 20 Aug 1971 [22 Aug 1970] 39196/71 Heading C2C  Novel compounds of the Formula I wherein R<SP>1</SP>, R<SP>2</SP> and R<SP>3</SP>, which may be the same or different, are each a hydrogen atom or an alkyl radical; R<SP>4</SP> is a hydrogen atom, an optionally substituted alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, or aralkynyl, aliphatic acyl, aromatic acyl, a group -R<SP>4#1</SP>-O-R<SP>4#11</SP> (where R<SP>4#1</SP> and R<SP>4#11</SP> 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 R<SP>12</SP> 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); R<SP>5</SP> is a hydrogen atom or an alkyl, alkenyl or alkynyl radical or an optionally substituted aryl radical; R<SP>6</SP> and R<SP>7</SP>, which may be the same or different, are each a hydrogen atom or an optionally substituted alkyl, alkenyl, alkynyl, or aryl radical; R<SP>8</SP>, R<SP>9</SP> and R<SP>10</SP>, 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-R<SP>11</SP> group (R<SP>11</SP> 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 R<SP>4</SP> is an aliphatic acyl, aromatic acyl or alkyl-, alkenyl- or aryl-sulphonyl radical, and that X cannot be -SO- or -SO 2 - when R<SP>4</SP> 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 R<SP>4</SP> 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 R<SP>4</SP> is hydrogen, reducing a compound wherein A is -CN or -COOR<SP>7#1</SP> (R<SP>7#1</SP> has the same meaning as R<SP>7</SP>); (e) for compounds in which n is zero, X is oxygen and R<SP>4</SP> is hydrogen, reducing a compound of the previous formula wherein A represents -COR<SP>7#1</SP> (R<SP>7#1</SP> has the same meaning as R<SP>7</SP>). 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.