New orally active enkephalinase inhibitors: their synthesis, biological activity, and analgesic properties
| Autor: | Masanori Kawamura, Kazuhiko Senokuchi, Yuuki Nagao, Hisao Nakai, Yasuhiro Sakai, Nobuo Katsube |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Magnetic Resonance Spectroscopy Clinical Biochemistry Analgesic Administration Oral Biological Availability Pharmaceutical Science Pharmacology Biochemistry Rats Sprague-Dawley Structure-Activity Relationship Dogs Animal model Oral administration Drug Discovery Animals Prodrugs Enzyme Inhibitors Molecular Biology Chromatography High Pressure Liquid Pain Measurement Analgesics Chemistry Organic Chemistry Enkephalinase Biological activity Enkephalins Analgesics Non-Narcotic Rats Butyrates Orally active Area Under Curve Molecular Medicine Neprilysin Chromatography Thin Layer |
| Zdroj: | Bioorganic & Medicinal Chemistry. 6:441-463 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/s0968-0896(97)10048-7 |
| Popis: | A series of (4 S )-4-[(2 S )-benzyl-3-mercaptopropionylamino]-4-( N -phenylcarbamoyl)-butyric acids has been identified as potent systemically active enkephalinase inhibitors. Structure–activity relationships (SAR) are discussed. Further chemical modification of the inhibitors was carried out in order to identify the inhibitors which are orally active in an animal model. Compounds of particular interest are the prodrug-like analogues, including 5b (ONO-9902). Their analgesic effects after oral administration were evaluated. |
| Databáze: | OpenAIRE |
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