SYNTHESIS OF NOVEL SUCCINAMIDE DERIVATIVES HAVING THE 1-DIHYDRO-6H-PYRIDO[2,3-B][1,4]BENZODIAZEPIN-6-ONE SKELETON AS POTENT AND SELECTIVE M-2 MUSCARINIC RECEPTOR ANTAGONISTS .1.

Authors
WATANABE T KINOYAMA I KAKEFUDA A OKAZAKI T TAKIZAWA K HIRANO S SHIBATA H YANAGISAWA I
Citation
T. Watanabe et al., SYNTHESIS OF NOVEL SUCCINAMIDE DERIVATIVES HAVING THE 1-DIHYDRO-6H-PYRIDO[2,3-B][1,4]BENZODIAZEPIN-6-ONE SKELETON AS POTENT AND SELECTIVE M-2 MUSCARINIC RECEPTOR ANTAGONISTS .1., Chemical and Pharmaceutical Bulletin, 45(6), 1997, pp. 996-1007
Citations number
36
Categorie Soggetti
Pharmacology & Pharmacy",Chemistry
Journal title
Chemical and Pharmaceutical Bulletin → ACNP
ISSN journal
00092363
Volume
45
Issue
6
Year of publication
1997
Pages
996 - 1007
Database
ISI
SICI code
0009-2363(1997)45:6<996:SONSDH>2.0.ZU;2-L
Abstract
A series of 1-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one derivat ives containing the succinamide skeleton has been synthesized and eval uated for M-1, M-2 and M-3 muscarinic receptor binding affinities (in vitro) and M-2 and M-3 muscarinic receptor antagonistic activities (in vivo). Some of them showed higher and more selective binding affiniti es for M-2 muscarinic receptors than that of AF-DX 116. Among them, 1- dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one (68) was found to be the most potent and selective M-2 muscarinic receptor antagonist in vi tro. This compound also strongly inhibited the oxotremorine-induced br adycardia after intravenous administration and showed 130-fold selecti vity for M-2 muscarinic receptors over M-3 muscarinic receptors in viv o.