Synthesis and biological evaluation of phenylacetyl derivatives having low central nervous system permeability as potent and selective M2 muscarinic receptor …

…, H SHIBATA, Y YAMAGIWA, I YANAGisAWA

Index: Watanabe, Toshihiro; Kakefuda, Akio; Tanaka, Akihiro; Takizawa, Kenji; Hirano, Seiko; Shibata, Hiroshi; Yamagiwa, Yoko; Yanagisawa, Isao Chemical and Pharmaceutical Bulletin, 1998 , vol. 46, # 1 p. 53 - 68

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Citation Number: 15

Abstract

A series of phenylacetyl derivatives containing the 5, 10-dihydro-11H-dibenzo [b, e][1, 4] diazepin-11-one or 5, 11-dihydro-6H-pyrido [2, 3-b][1, 4] benzodiazepin-6-one skeleton was prepared and evaluated for their binding affinities to muscarinic receptors in vitro and for antagonism of bradycardia, salivation and tremor in vivo. Among them, compounds 56 and 66 had high affinity for M 2 muscarinic receptors in the heart (pK i= 8.7 and 8.9, ...