GB836332A - Novel amino-acid hydrazides and a process for the manufacture of same - Google Patents

Abstract

The invention comprises amino-acid hydrazides of formula <FORM:0836332/IV (b)/1> where R1 is an aralkyl radical or a C1-7, alicyclic or aliphatic hydrocarbon radical, R2 is hydrogen or a hydrocarbon radical which may contain oxygen, nitrogen and/or sulphur atoms, R3 is hydrogen or alkyl and R4 is hydrogen, alkyl or acyl and R2 and R3 and R4 may be linked to form a heterocyclic ring, and salts thereof. A list of salt-forming acids includes ascorbic acid. Preparative methods specified are: (1) reaction of amino-acids with substituted hydrazines in the presence of a carbodiimide, e.g. at room temperature or slightly above, conveniently in aqueous or organic solution; (ii) reacting a reactive amino-acid derivative such as the ester, halide, amide or anhydride with a substituted hydrazine, preferably by heating a mixture under reflux; (iii) heating the substituted-hydrazine salts of the amino-acids to a temperature at which the salts dehydrate, advantageously removing the water formed continuously; (iv) reacting an amino-acid hydrazide with a carbonyl compound and reducing the resulting hydrazone simultaneously or successively e.g. by hydrogenation or with lithium aluminium hydride or by treating the hydrazone with a Grignard reagent and and hydrolysing the resulting product. In the above processes the group R4 may be chosen as an acyl group which is readily removable by alkaline hydrolysis (e.g. trifluoroacetyl) or hydrogenolysis (e.g. carbobenzyloxy). The products act as amine oxidase inhibitors and have therapeutic uses. Starting materials prepared are: in Example 11, DL-allo-carbobenzyloxythreonine and in Example 19, DL-threo-N-carbobenzyloxy-b -phenylserine by carbobenzyloxylation of the corresponding amino-acids; in Example 22, DL-a -dimethylamino propionic acid, which is converted to its ethyl ester, by reacting a -bromopropionic acid with dimethylamine; in Example 23, DL-a -methylaminopropionic acid and its methyl ester are similarly prepared using methylamine.