Synthesis and biological evaluation of 1, 2, 3, 4-tetrahydroisoquinoline derivatives as potent and selective M2 muscarinic receptor antagonists.

T Watanabe, I Kinoyama, K Takizawa…

Index: Watanabe, Toshihiro; Kinoyama, Isao; Takizawa, Kenji; Hirano, Seiko; Shibanuma, Tadao Chemical and Pharmaceutical Bulletin, 1999 , vol. 47, # 5 p. 672 - 677

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Citation Number: 7

Abstract

A series of 1, 2, 3, 4-tetrahydroisoquinoline derivatives containing the 5, 11-dihydro-6H- pyrido [2, 3-b][1, 4] benzodiazepin-6-one skeleton were prepared and evaluated for their in vitro binding affinities to muscarinic receptors and for antagonism of bradycardia in vivo. Among them, compound 3f had the highest affinity for M 2 muscarinic receptors in the heart (pKi= 9.1) with low affinity for M 3 muscarinic receptors in the submandibular gland. A ...