ChemInform Abstract: SYNTHESIS AND STUDY OF DIPEPTIDYLCARBOXYPEPTIDASE INHIBITORS ‐ N‐MERCAPTOACYLATED SUBSTITUTED 2‐PIPERIDINECARBOXYLIC ACIDS

Abstract

Die N‐Thioacyl‐piperidincarbonsäuren (III), (V) und (VI) werden als Analoga des Wirkstoffes "Captopril" (VII), eines Medikamentes zur Behandlung des arteriellen Bluthochdruckes, hergestellt.

Synthesis of (2S,4S)-2-Substituted-3- (3-Sulfanylpropanoyl)-6- Oxohexahydropyrimidine-4-Carboxylic Acids as Potential Antihypertensive Drugs

“…3-(Acetylsulfanyl)propanoyl chloride was obtained by the method [20]. 3-(3-sulfanylpropanoyl)-2-alkyl(aryl)-6-oxohexahydropyrimidine-4-carboxylic acids 4а-i, potential antihypertensive drugs, ACE inhibitors [21]; the compounds otained are structural analogs of the known antihypertensive drug methiapril, (2S,6S)-1-[(3-acetylsulfanyl)propanoyl]-6-methylpipecolinic acid [7]. However unlike methiapril whose production requires difficultly available synthetic (2S,6S)-6-methylpipecolinic acid [22], the stereoselective synthesis of compounds 4а-i is underlain by natural or commercially available reagents.…”

“…The first of the drugs from this series was captopril, (S)-N-(3-sulfanyl-2-methyl-1-oxopropyl)-L-proline [4]. The later research on development of antihypertensive substances, ACE inhibitors, was directed to the replacement of the natural amino acid L-proline in the captopril molecule by synthetic cyclic amino acids of the heterocyclic series, among them derivatives of 1,3-oxazolidine [5], 1,3-thiazolidine [6], pipecoline [7], quinazoline [8], indole [9], and azepine [10]. In the series of the saturated pyrimidine derivatives the only example of the inhibitor activity with respect to ACE is known to be shown by 3-(3-sulfanylpropanoyl)-6-oxohexahydropyrimidine-4-carboxylic acid [11].…”