新型脂肪酸氧化抑制剂，效力增强且无不良代谢和电生理特性。
New fatty acid oxidation inhibitors with increased potency lacking adverse metabolic and electrophysiological properties.
作者信息
Koltun Dmitry O, Marquart Timothy A, Shenk Kevin D, Elzein Elfatih, Li Yuan, Nguyen Marie, Kerwar Suresh, Zeng Dewan, Chu Nancy, Soohoo Daniel, Hao Jia, Maydanik Victoria Y, Lustig David A, Ng Khing Jow, Fraser Heather, Zablocki Jeffery A
机构信息
Department of Bioorganic Chemistry, 3172 Porter Dr., Palo Alto, CA 94304, USA.
出版信息
Bioorg Med Chem Lett. 2004 Jan 19;14(2):549-52. doi: 10.1016/j.bmcl.2003.09.093.
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.
基于一种结构新颖的先导化合物CVT-3501（1）合成了棕榈酰辅酶A氧化的新型抑制剂。针对心脏线粒体棕榈酰辅酶A氧化的抑制效力和代谢稳定性进行了构效关系研究。对强效且代谢稳定的类似物33、42和43进行了体外细胞色素P450抑制作用及潜在不良电生理效应的评估。还发现化合物33在大鼠体内具有良好的药代动力学性质。
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