4-氨基-3,4-二氢-2H-1-苯并吡喃-3-醇和4-氨基-2H-1-苯并吡喃对豚鼠离体气管的松弛活性

Relaxant activity of 4-amido-3,4-dihydro-2H-1-benzopyran-3-ols and 4-amido-2H-1-benzopyrans on guinea pig isolated trachealis.

作者信息

Buckle D R, Arch J R, Fenwick A E, Houge-Frydrych C S, Pinto I L, Smith D G, Taylor S G, Tedder J M

机构信息

SmithKline Beecham Pharmaceuticals, Biosciences Research Centre, Epsom, Surrey, England.

出版信息

J Med Chem. 1990 Nov;33(11):3028-34. doi: 10.1021/jm00173a019.

DOI:10.1021/jm00173a019

PMID:2231602

Abstract

A series of 4-amido-3,4-dihydro-2H-1-benzopyran-3-ols and 4-amido-2H-1-benzopyrans related to the potassium channel activator cromakalim have been prepared and evaluated for their relaxant activity in guinea pig isolated tracheal spirals. Several analogues show enhanced relaxant activity relative to cromakalim in this preparation and the rank order of potency for those substituents investigated at C-6 was CF3 greater than CN greater than C2H5 greater than aza greater than or equal to CH3. One compound, trans-3,4-dihydro-2,2-dimethyl-4-(2-oxopiperidin-1-yl)-7-(trifluor omethyl)-2H- 1-benzopyran-3-ol (24), was resolved into its two enantiomers and the activity was shown to reside essentially in the (+)-isomer, adding further support to the suggestion that the smooth muscle receptor for these potassium channel activators is stereoselective.

摘要

已经制备了一系列与钾通道激活剂克罗卡林相关的4-酰胺基-3,4-二氢-2H-1-苯并吡喃-3-醇和4-酰胺基-2H-1-苯并吡喃，并在豚鼠离体气管螺旋条中评估了它们的舒张活性。在该制剂中，几种类似物相对于克罗卡林显示出增强的舒张活性，在C-6处研究的那些取代基的效价顺序为CF3大于CN大于C2H5大于氮杂大于或等于CH3。一种化合物，反式-3,4-二氢-2,2-二甲基-4-(2-氧代哌啶-1-基)-7-(三氟甲基)-2H-1-苯并吡喃-3-醇(24)，被拆分为其两种对映体，并且活性基本上存在于(+)-异构体中，这进一步支持了这些钾通道激活剂的平滑肌受体具有立体选择性的观点。