Substituted Tetrahydropyrrolo[2,1-b]oxazol-5(6H)-ones and Tetrahydropyrrolo[2,1-b]thiazol-5(6H)-ones as Hypoglycemic Agents
| Autor: | Cheon Seung Hoon, Leonard J. Brand, Jeffrey Nadelson, Christina L. Leone, Rhonda O. Deems, Howard C. Smith, Douglas C. Knorr, Philip A. Bell, William S. Fillers, Thomas Daniel Aicher, Fell Jay Bradford, Ronald Simpson, Bork Balkan, Fraser James D, Gerald G. Kahle, Jiaping Gao |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Stereochemistry Drug Evaluation Preclinical Chemical synthesis Cell Line Mice Structure-Activity Relationship chemistry.chemical_compound In vivo Drug Discovery Animals Hypoglycemic Agents Potency Structure–activity relationship Pyrroles Oxazoles Bicyclic molecule Chemistry Muscles Type 2 Diabetes Mellitus In vitro Rats Mice Inbred C57BL Thiazoles Glucose Diabetes Mellitus Type 2 Lactam Molecular Medicine |
| Zdroj: | Journal of Medicinal Chemistry. 41:4556-4566 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm9803121 |
| Popis: | A series of substituted tetrahydropyrrolo[2,1-b]oxazol-5(6H)-ones and tetrahydropyrrolo[2,1-b]thiazol-5(6H)-ones was synthesized from amino alcohols or amino thiols and keto acids. A pharmacological model based on the results obtained with these compounds led to the synthesis and evaluation of a series of isoxazoles and other monocyclic compounds. These were evaluated for their ability to enhance glucose utilization in cultured L6 myocytes. The in vivo hypoglycemic efficacy and potency of these compounds were evaluated in a model of type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus), the ob/ob mouse. 25a(2S) (SDZ PGU 693) was selected for further pharmacological studies. |
| Databáze: | OpenAIRE |
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