PHENOXY-ALKYL-CARBOXYLIC ACID DERIVATIVES AND PROCESS FOR THEIR PREPARATION

摘要

1359264 Benzoylaminoalkylphenoxyalkylcarboxylic acid compounds BOEHRINGER MANNHEIM GmbH 27 Sept 1972 [1 Oct 1971 22 June 1972] 44611/72 Heading C2C Novel compounds of the Formula (I): where R 1 and R 2 , which may be the same or different, are hydrogen or halogen atoms, alkyl or alkoxy groups, R 3 and R 4 are hydrogen or alkyl radicals, n is 1, 2 or 3 and Z is a hydroxyl group or an alkoxy radical, and the pharmacologically compatible salts thereof, may be obtained by reacting an amine of the general Formula II: optionally after introduction of a conventional protective group for the amino or hydroxyl group (which is subsequently slip off) with a derivative of an acid of the Formula III: and with a compound of the general formula (IV) in which X is a halogen atom or the residue of a sulphonic acid. Thus (III) may be reacted with (II) to form a di-benzoyl derivative which is partially hydrolysed to a N-benzoyl derivative and then reacted with (IV) to yield (I). Alternatively an N-acetyl derivative of (II) is reacted with (IV) and the intermediate is hydrolysed to remove the acetyl group, the acid group is reesterified and the intermediate is rea ted with (III) to form (I). The preparation of the following intermediates is also described: 3,(4-hydroxyphenyl)-propionic acid is reacted with benzoyl chloride forming benzyl 3-(4-benzyloxyphenyl)- propionate which is hydrolysed to 3-(4-benzyloxyphenyl)-propionic acid, then reacted with ethyl chloroformate and ammonia to form 3-(4- benzyloxyphenyl)-propionamide which is reduced with LiAlH 4 to form 3-(4-benzyloxyphenyl)-propylamine, obtained as HCl salt. Pharmaceutical compositions showing considerable lowering of the serum lipid level and cholesterol level comprise compounds of Formula (I) above in admixture with a solid or liquid pharmaceutical diluent or carrier.