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首页> 外文期刊>Bioorganic and medicinal chemistry >3-(2-Aminocarbonylphenyl)propanoic acid analogs as potent and selective EP3 receptor antagonists. Part 3: Synthesis, metabolic stability, and biological evaluation of optically active analogs.
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3-(2-Aminocarbonylphenyl)propanoic acid analogs as potent and selective EP3 receptor antagonists. Part 3: Synthesis, metabolic stability, and biological evaluation of optically active analogs.

机译:3-(2-氨基羰基苯基)丙酸类似物作为有效的和选择性的EP3受体拮抗剂。第3部分:旋光类似物的合成,代谢稳定性和生物学评估。

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摘要

A series of 3-(2-aminocarbonylphenyl)propanoic acid analogs possessing the (1R)-1-(3,5-dimethylphenyl)-3-methylbutylamine moiety on the carboxyamide side chain were synthesized and evaluated for their binding affinity for the EP1-4 receptors and their antagonist activity for the EP3 receptor. Rational drug design based on the structure of the metabolites in human liver microsomes led us to the discovery of another series of analogs. Several compounds were further evaluated for their in vivo efficacy in rats after oral administration and also for their pharmacokinetic profiles including in vitro stability in the liver microsomes.
机译:合成了一系列在羧酰胺侧链上具有(1R)-1-(3,5-二甲基苯基)-3-甲基丁胺部分的3-(2-氨基羰基苯基)丙酸类似物,并评估了它们对EP1-的结合亲和力4种受体及其对EP3受体的拮抗活性。基于人肝微粒体中代谢物结构的合理药物设计使我们发现了另一系列类似物。进一步评价了几种化合物在口服给药后在大鼠中的体内功效以及药代动力学特征,包括在肝微粒体内的体外稳定性。

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