New fatty acid oxidation inhibitors with increased potency lacking adverse metabolic and electrophysiological properties
| Autor: | Kevin D. Shenk, Heather Fraser, Khing Jow Ng, Jia Hao, David Lustig, Elfatih Elzein, Timothy A. Marquart, Suresh S. Kerwar, Dmitry Koltun, Daniel Soohoo, Dewan Zeng, Nancy Chu, Victoria Y. Maydanik, Marie Nguyen, Yuan Li, Jeffery A. Zablocki |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.drug_class
Clinical Biochemistry Guinea Pigs Racemases and Epimerases Pharmaceutical Science Carboxamide Mitochondrion In Vitro Techniques Biochemistry Chemical synthesis Pharmacokinetics Drug Stability Drug Discovery medicine Potency Animals Enzyme Inhibitors Molecular Biology Beta oxidation Enoyl-CoA Hydratase biology Chemistry Organic Chemistry Cytochrome P450 3-Hydroxyacyl CoA Dehydrogenases Acetyl-CoA C-Acyltransferase Carbon-Carbon Double Bond Isomerases In vitro Rats Electrophysiology biology.protein Molecular Medicine |
| Zdroj: | Bioorganicmedicinal chemistry letters. 14(2) |
| ISSN: | 0960-894X |
| Popis: | New inhibitors of palmitoylCoA oxidation were synthesized based on a structurally novel lead, CVT-3501 (1). Investigation of structure-activity relationships was conducted with respect to potency of inhibition of cardiac mitochondrial palmitoylCoA oxidation and metabolic stability. Potent and metabolically stable analogues 33, 42, and 43 were evaluated in vitro for cytochrome P450 inhibition and potentially adverse electrophysiological effects. Compound 33 was also found to have favorable pharmacokinetic properties in rat. |
| Databáze: | OpenAIRE |
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