Patent GB-1267168-A (GB)
IPC: C07C59/70
Filed: 1969-10-08
Abstract: 1,267,168. Bis-substituted phenoxy acetic acids. SANDOZ Ltd. 8 Oct., 1969 [18 Oct., 1968], No. 49343/69. Heading C2C. The invention comprises compounds of the Formula I wherein R represents a hydrogen atom or the residue of a monohydric alcohol, R 1  and R 2  each represent a hydrogen, chlorine, bromine or iodine atom or a trifluoromethyl phenyl, pchlorophenyl, p-bromophenyl or p-iodophenyl radical, R 3  and R 4  each represent a hydrogen, chlorine, bromine or iodine atom provided that (i) at least one of R 1  and R 2  is other than hydrogen, (ii) when R 1 =R 2 =chlorine and R 3 =R 4 = hydrogen R does not represent a hydrogen atom, an alkyl C 1-6 , piperidino, cyanomethyl, di-(carbalkoxy C 1-4 )-methyl or a residue A of an alcohol AOH where A is a group -(CHR<SP>0</SP>) n R<SP>1</SP> or a group of the Formulµ II, III, IV, V, VI, VII or a 2-dimethyl-2-methylpropyl or a N-(#-P. chlorophenoxyethyl)-piperidino group, n is an integer from 1 to 4 and R<SP>1</SP> is a group of the Formulµ II, III, IV, V, VI and VII or of the formulµ or a cycloalkylamino C 6-8  radical, a dibenzazepinyl radical or a -NR 7 R 8  radical and when n is 2, 3 or 4 and R<SP>0</SP> is a hydrogen atom, R<SP>1</SP> also represents an anilino, N-alkyl C 1-4  anilino or a N - (# - p - chlorophenoxyethyl)pyrrolidine radical; R<SP>0</SP> is a hydrogen atom or an alkyl C 1-4  radical, R 5  is a hydrogen, chlorine or bromine atom or an alkyl C 1-4  radical, R 6  is an alkyl C 1-4 , propargyl, phenyl, chloro- or bromophenyl or a phenyl-alkyl C 1-4  radical, R 7  is a hydrogen atom, an alkyl C 1-4 , cycloalkyl C 5-7  phenyl, phenyl-alkyl C 1-4 , 1- or 2-naphthyl group, R 8  is an alkyl C 1-4 , cycloalkyl C 5-7 , phenyl, phenyl-alkyl C 1-4  radical, provided that when R 7  is a hydrogen atom R 8  is a phenyl radical, (iii) R 1 -R 4  may each represent a hydrogen, chlorine, bromine or iodine atom when R does not represent a hydrogen atom or an alkyl C 1-6  radical, (iv) R 1  = R 2  and represents a trifluoromethyl, phenyl, p-chloro- or p-bromophenyl radical and R 3  = R 4  = hydrogen only when R does not represent a hydrogen atom or an alkyl C 1-6  radical or a group of formula where n<SP>11</SP> is 0 to 4, n<SP>111</SP> is 4 or 5 and Ry 2  is an alkyl C 1-4  radical and (v) R 1  and R 2  may each represent a trifluoromethyl or phenyl radical or a hydrogen atom, and R 3  and R 4  are both hydrogen only when R does not represent a hydrogen atom or an alkyl C 1-6  radical, (vi) R represents a radical of the formula only when R 1  and R 2  are not both chlorine and R 3  and R 4  are not both hydrogen. They may be prepared by a variety of methods. α-Bromo-p-bromophenoxy acetic acid methyl ester is prepared by brominating p-bromophenoxy acetic acid methyl ester prepared from methyl chloroacetate and p-bromophenol. α - Bromo - p - trifluoromethylphenoxy acetic acid is prepared by reacting bromine with ptrifluoromethyl phenoxyacetic acid, prepared from p-trifluoromethyl phenol and chloroacetic acid. Pharmaceutical compositions containing as active ingredient a compound of Formula I or a pharmaceutically acceptable quaternary ammonium or acid addition salt thereof together with an inert diluent or carrier are administered orally and have hypocholesteremic/hypolipemic activity.