Hypotensive mercaptoacyl-proline derivs. - prepd. by acylating proline or its analogues with mercapto-carboxylic acid derivs. (BE 11.8.77)

摘要

Cpds. of formula (I) and theis basic salts are new. In the formula, R is OH, amino or lower alkoxy; R1 and R4 are H, lower alkyl, phenly or phenyl-(lower alkyl); R2 is H, lower alkyl, phenyl (opt. substd. by halogen, lower alkyl or lower alkoxy), phenyl-(lower alkyl), diphenyl-(lower alkyl), triphenyl-(lower alkyl), lower alkylthiomethyl, phenyl-(lower alkylthiomethyl), lower alkanoylaminomethyl, -COR5, -C(=M)-M-R5, -C(=M)-NHR5, -SR6 or R7; R3 is H, OH or lower alkyl; R5 is lower alkyl, phenyl or phenyl-(lower alkyl); R6 is lower alkyl, hydroxy-(lower alkyl), amino (carboxy)-substd. lower alkyl, phenyl, or phenyl substd. by halogen, lower alkyl or lower alkoxy; R7 is a residue of formula (Ia) M is O or S; m is 1, 2 or 3; and n and p are 0, 1 or 2. (I) may be in the form of optical isomers or racemates (asterisks in formula (I) indicate asymmetric centres). (I) are blockers of angiotensin converting enzyme. They inhibit conversion of angiotensin I into the hypertensive angiotensin II, and thus reduce or eliminate angiotensin-induced hypertension. (I) can be administered orally or parenterally. Dosage for reducing blood pressure is pref. ca. 1-50 mg/kg/day. Specific (I) include 1-(2-benzoylthioacetyl)-L-proline, prepd. e.g. by acylating L-proline with chloroacetyl chloride in the presence of NaOH and reacting the product with thiobenzoic acid in the presence of K2CO3.