Synthesis of novel angiotensin converting enzyme inhibitor quinapril and related compounds. A divergence of structure-activity relationships for non-sulfhydryl and sulfhydryl types
| Autor: | M. L. Hoefle, Holmes A, I. Nordin, J. M. Hinkley, R. W. Fleming, A. E. Werner, Cohen Dm, Essenburg Ad, Klutchko S, Blankley Cj |
|---|---|
| Rok vydání: | 1986 |
| Předmět: |
Male
Stereochemistry Molecular Conformation Angiotensin-Converting Enzyme Inhibitors Structure-Activity Relationship In vivo Tetrahydroisoquinolines Drug Discovery medicine Animals Potency Sulfhydryl Compounds Proline Enalapril biology Chemistry Quinapril Rats Inbred Strains Angiotensin-converting enzyme Isoquinolines Small molecule Rats Biochemistry Enzyme inhibitor biology.protein Molecular Medicine medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 29:1953-1961 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00160a026 |
| Popis: | The synthesis and angiotensin converting enzyme (ACE) inhibiting activities of quinapril (CI-906, 22), its active diacid (CI-928, 33), and its dimethoxy analogue (CI-925, 25) are reported. These tetrahydro-3-isoquinolinecarboxylic acid derivatives possess equivalent in vitro potency and in vivo efficacy to enalapril. Sulfhydryl analogues with the same structural variation are also highly potent. In contrast, tetrahydro-1-isoquinolinecarboxylic acid and homologous isoindoline-1-carboxylic acid analogues show a striking divergence in potency between the two types, sulfhydryl analogues being essentially inactive, while non-sulfhydryl analogues are equipotent with the proline prototype. This is the first evidence suggesting that alternate binding modes may exist for the two major structural classes of small molecule ACE inhibitors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|