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首页> 外文期刊>Japanese Journal of Pharmacology >Studies on Serotonin (5-HT)3-Receptor Antagonist Effects of Enantiomers of 4, 5, 6, 7-Tetrahydro-1H-Benzimidazole Derivatives
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Studies on Serotonin (5-HT)3-Receptor Antagonist Effects of Enantiomers of 4, 5, 6, 7-Tetrahydro-1H-Benzimidazole Derivatives

机译：4、5、6、7-四氢-1H-苯并咪唑衍生物的对映体的5-羟色胺（5-HT）3-受体拮抗作用研究

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References(26) Cited-By(4) We assessed the 5-HT3-receptor antagonist effects of 4, 5, 6, 7-1H-benzimidazole compounds which are derivatives of YM060, a potent and selective 5-HT3-receptor antagonist, in isolated guinea pig colon. YM114 (KAE-393), YM-26103-2, YM-26308-2 (3 × 10-9 to 3 × 10-8 M) produced concentration-dependent shifts to the right of the dose-response curves for both 5-HT and 2-methyl-5-HT (2-Me-5-HT). YM114 (pA2=9.08 against 5-HT, pA2=8.88 against 2-Me-5-HT), YM-26103-2 (pA2=8.27 against 5-HT, pA2 = 8.19 against 2-Me-5-HT), and YM-26308-2 (pA2 = 8.58 against 5-HT, pA2 = 8.4 against 2-Me-5-HT) showed similar pA2 values irrespective of the agonist used, suggesting that they have 5-HT3-receptor blocking activity irrespective of the N-position at the aromatic ring. Since these compounds have an asymmetric center, their enantiomers exist. The S-isomers were one to three orders of magnitude less potent than the respective R-isomer compounds, indicating that the stereochemical configuration of 4, 5, 6, 7-tetrahydro-1Hbenzimidazoles is an important determinant of their affinity for 5-HT3 receptors. These results suggest that the highly potent 5-HT3 receptor antagonism and high selectivity for 5-HT3 receptors of 4, 5, 6, 7-tetrahydro-1H-Benzimidazole derivatives are conserved irrespective of the position of the nitrogen atom in the aromatic ring and that 5-HT3, recentors favor the R-isometric conformation of these compounds.
机译：参考文献（26）Cited-By（4）我们评估了4、5、6、7-1H-苯并咪唑化合物（一种有效且选择性的5-HT3受体拮抗剂YM060的衍生物）的5-HT3受体拮抗剂的作用，在孤立的豚鼠结肠中。 YM114（KAE-393），YM-26103-2，YM-26308-2（3×10-9至3×10-8 M）在5个剂量响应曲线的右侧都产生了浓度依赖性位移HT和2-甲基-5-HT（2-Me-​​5-HT）。 YM114（针对5-HT的pA2 = 9.08，针对2-Me-​​5-HT的pA2 = 8.88），YM-26103-2（针对5-HT的pA2 = 8.27，针对2-Me-​​5-HT的pA2 = 8.19），和YM-26308-2（针对5-HT的pA2 = 8.58，针对2-Me-​​5-HT的pA2 = 8.4）显示相似的pA2值，而与所使用的激动剂无关，这表明它们具有5-HT3受体阻滞活性，而与使用的激动剂无关。芳环的N位由于这些化合物具有不对称中心，因此它们的对映异构体存在。 S异构体的效力比各自的R异构体化合物低1-3个数量级，表明4，5，6，7-四氢-1H苯并咪唑的立体化学构型是其对5-HT3受体亲和力的重要决定因素。这些结果表明，无论氮原子在芳族环和芳香族环中的位置如何，都可以有效保护4-，5、6、7-四氢-1H-苯并咪唑衍生物的5-HT3受体拮抗作用和对5-HT3受体的高选择性。由于5-HT3，最近的研究者赞成这些化合物的R-等距构象。

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