Patent IE-32673-B1 (IE)
Title: Pharmaceutical compositions
IPC: A61K31/19
Filed: 1968-11-11
Abstract: 1,235,734. Bis-phenoxy-acetic acid derivatives. SANDOZ Ltd. 12 Nov., 1968 [13 Nov., 1967], No. 53604/68. Heading C2C. Bis-phenoxy-acetic acid derivatives of the general formula wherein R is a hydrogen or alkali metal atom or a straight or branched chain C 1-6 alkyl group and R 1 , R 2 , R 3 and R 4 are each a hydrogen, chlorine, bromine or iodine atom, provided that at least one of R 1 and R 2 is other than a hydrogen atom and that when R is a hydrogen atom or a methyl or ethyl group (i) at least one of R 1 , R 2 , R 3 and R 4 must be other than a chlorine atom and (ii) when R 3 and R 4 are both hydrogen atoms, at least one of R 1 and R 2 must be other than a chlorine atom, are prepared (a) when R 1 is the same as R 2 and is other than a hydrogen atom and R 3 is the same as R 4 , by reaction of a compound of the general formula as a phenolate or in the presence of a hydrohalic acid binding agent, with a dihaloacetic acid derivative of the general formula X 2 CHCOOR, wherein X is a chlorine, bromine or iodine atom; (b) by partial decarboxylation of a bis-phenoxy-malonic acid derivative of the general formula (c) by reaction of an α-halo-phenoxyacetic acid derivative of the general formula with a compound of the general formula as a phenolate or in the presence of a hydrohalic acid binding agent; (d) with the provisos (i) when R is other than an alkali metal atom and (ii) when R is other than a hydrogen atom or a methyl or ethyl group and R 3 and R 4 are both hydrogen atoms, R 1 and R 2 are not both chlorine atoms, by reaction of a bis-phenoxyacetic acid derivative of the general formula wherein Y is a hydroxyl group or a chlorine or bromine atom, with a compound of the general formula ROZ, wherein Z is a hydrogen or alkali metal atom, provided that when Y is a hydroxyl group Z is a hydrogen atom; and (e) when R is a hydrogen atom, by saponification of the corresponding bis-phenoxy-acetic acid derivative of the first general formula above, wherein R is a straight or branched chain C 1-6 alkyl group. Bis-phenoxy-acetic acid derivatives of the first general formula above, wherein R is a hydrogen atom or a straight or branched chain C 1-6 alkyl group and R 1 , R 2 , R 3 and R 4 are as defined above, with the provisos (i) that at least one of R 1 and R 2 is other than a hydrogen atom; (ii) that when R 3 and R 4 are both hydrogen atoms, at least one of R 1 and R 2 is other than a chlorine atom; and (iii) that when R is a hydrogen atom or a methyl or ethyl group, at least one of R 1 , R 2 , R 3 and R 4 is other than a chlorine atom, and base addition salts thereof when R is a hydrogen atom are novel compounds. α-Halophenoxyacetic acid derivatives of the fifth general formula above are prepared by reaction of a compound of the second general formula above as a phenolate or in the presence of a hydrohalic acid binding agent with a haloacetic acid derivative of the general formula XCH 2 COOR, followed by halogenation of the resulting phenoxyacetic acid derivative of the general formula Pharmaceutical compositions having hypocholesteremic and hypolipemic activity comprise, as active ingredient, a novel bis-phenoxyacetic acid derivative as defined in the second paragraph above, together with a pharmaceutically acceptable diluent or carrier and may be administered orally.
[GB1235734A]