In the course of continuing efforts to develop potent and bladder-selective muscarinic M3 receptor antagonists, quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives and related compounds were designed as conformationally restricted analogues of quinuclidin-3-yl benzhydrylcarbamate (8). Binding assays with rat muscarinic receptor subtypes revealed that the quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives showed high affinities for the M3 receptor, and selectivity for the M3 receptor over the M2 receptor. Of these derivatives, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monohydrochloride (9b) exhibited almost the same inhibitory activity against bladder contraction to that of oxybutynin (1), and more than 10-fold selectivity for bladder contraction versus salivary secretion, demonstrating that 9b may be useful for the treatment of symptoms associated with overactive bladder without having side effects such as dry mouth.

中文翻译：

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作为新型毒蕈碱受体拮抗剂的奎宁丁-3-基1,2,3,4-四氢异喹啉-2-羧酸衍生物的合成及抗毒蕈碱特性。

在继续努力开发有效的和对膀胱有选择性的毒蕈碱型M3受体拮抗剂的过程中，将奎尼丁3-基1-芳基-1,2,3,4-四氢异喹啉-2-羧酸酯衍生物和相关化合物设计为受构象限制的类似物奎宁丁-3-基苄基氨基甲酸酯（8）。与大鼠毒蕈碱受体亚型的结合测定表明，奎宁环素-3-基1-芳基1,2,3,4-四氢异喹啉-2-羧酸酯衍生物显示出对M3受体的高亲和力以及对M3受体的选择性高于M2受体。在这些衍生物中，（+）-（1S，3'R）-奎宁环素-3'-基-1-苯基-1,2-，3,4-四氢异喹啉-2-羧酸盐单盐酸盐（9b）表现出几乎相同的抑制活性。膀胱收缩至奥昔布宁（1），