Patent GB-1023204-A (GB)
Title: New amino acids and process for their manufacture
IPC: C07C45/68
Filed: 1963-08-19
Abstract: The invention comprises compounds of formula <FORM:1023204/C2/1> wherein Ph is a phenyl group carrying in the meta-position a halogen or trifluoromethyl group and also carrying a free or etherified hydroxyl group, which phenyl group may be further substituted by one or more substituents selected from hydroxyl groups, etherified hydroxyl groups and halogen atoms, and R represents an alkyl (1-6 C) group; their salts; and their preparation by (1) hydrolysis of corresponding hydantoins, (2) hydrolysis of corresponding N-alkanoyl compounds, (3) hydrolysis of resulting compounds containing etherified hydroxyl groups. Resolution of isomers is mentioned. Starting compounds of which the preparation is described are:-3-fluoro-4-methoxybenzyl bromide, 3 - fluoro - 4 - methoxybenzyl cyanide, a  - cyano - a  - (3 - fluoro - 4 - methoxyphenyl) - acetone, 3 - fluoro - 4 - methoxyphenyl acetone, 4 - methyl - 4 - (31 - fluoro - 41 - methoxybenzyl)-hydantoin, and corresponding 3 - bromo - compounds; 2 - fluoro - 4 - bromoanisole; a  - acetyl - a  - methyl - b  - (2 - methoxy - 5 - fluorophenyl)-propionic acid ethyl ester, N-acetyl - a  - methyl - 2 - methoxy - 5 - fluorophenyl-alanine and its ethyl ester; 3-chloro-4-methoxybenzyl chloride, 3-chloro-4-methoxybenzyl cyanide, a -cyano-a -(3-chloro-4-methoxyphenyl) - acetone, 3 - chloro - 4 - methoxyphenyl - acetone, 4 - methyl - 4 - (31 - chloro - 41 - methoxybenzyl) - hydantoin; a  - methyl - a  - acetyl - b  - (3 - chloro - 4 - methoxyphenyl) - propionic acid ethyl ester, a -methyl-N-acetyl-3-chloro - 4 - methoxyphenyl - alanine and its ethyl ester, and corresponding a -methyl-2-methoxy - 5 - chlorophenyl compounds, a  - ethyl - 2 - methoxy - 5 - chlorophenyl compounds, a - ethyl - 2 - methoxy - 5 - bromophenyl compounds, and a -n-butyl-2-methoxy- 5 - chlorophenyl compounds; 1 - cyano - 1 - (3 - chloro - 4 - methoxyphenyl) - butanone - (2), 1 - (3 - chloro - 4 - methoxyphenyl) - butanone - (2), 4 - ethyl - 4 - (31 - chloro - 41 - methoxybenzyl) - hydantoin; 3 - chloro - 4 - ethoxy - benzyl chloride, 3 - chloro - 4 - ethoxy - benzyl cyanide, a  - cyano - a  - (3 - chloro - 4 - ethoxyphenyl)-acetone, 3 - chloro - 4 - hydroxyphenyl - acetone and 4 - methyl - 4 - (31 - chloro - 4 - hydroxybenzyl) - hydantoin; N - acetyl - a  - methyl - 3 - iodo - 4 - hydroxy - phenyl alanine and the 3,5-diiodo-compound.ALSO:Pharmaceutical compositions comprise, with carriers, phenylalanines of general formula <FORM:1023204/A5-A6/1> wherein Ph represents a phenyl group carrying in the meta-position a halogen or trifluoromethyl group and also carrying a free or etherified hydroxyl group, which phenyl group may be further substituted by one or more substituents selected from hydroxyl groups, etherified hydroxyl groups and halogen atoms, and R represents an alkyl (1-6C) group, and their salts.  Oral and parenteral preparations of the compounds, which have hypotensive activity, are mentioned (e.g. tablets, pills, capsules, solutions, suspensions, emulsions).  Other antihypertensives may be present (e.g. reserpine, rescinnamine, deserpidine, syrosingopine, germine, protoveratrine, chlorthiazide, hydrochlorothiazide, cyclopenthiazide, 1-keto-3-(31-sulphamyl-41-chlorophenyl) -3-hydroxyisoindoline, hydralazine, dihydralazine, guanethidine, chlorisondamine).