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

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 M2 muscarinic receptors in the heart (pKi = 9.1) with low affinity for M3 muscarinic receptors in the submandibular gland. A structure-activity relationship (SAR) study suggested that the benzene ring fused piperidine and the alkyl linker chain length are crucially important for increased M2 affinity.

authors

Watanabe T,Kinoyama I,Takizawa K,Hirano S,Shibanuma T

doi

10.1248/cpb.47.672

subject

Has Abstract

pub_date

1999-05-01 00:00:00

pages

672-7

issue

5

eissn

0009-2363

issn

1347-5223

journal_volume

47

pub_type

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