Title of article
Metabolic stabilization of benzylidene ketal M2 muscarinic receptor antagonists via halonaphthoic acid substitution
Author/Authors
Craig D. Boyle، نويسنده , , Samuel Chackalamannil، نويسنده , , John W. Clader، نويسنده , , William J. Greenlee، نويسنده , , Hubert B. Josien، نويسنده , , James J. Kaminski، نويسنده , , Joseph A. Kozlowski، نويسنده , , Stuart W. McCombie، نويسنده , , Dennis V. Nazareno، نويسنده , , Jayaram R. Tagat، نويسنده , , Yuguang Wang، نويسنده , , Guowei Zhou، نويسنده , , William Billard، نويسنده , , Herbert Binch III، نويسنده , , Gordon Crosby، نويسنده , , Mary Cohen-Williams، نويسنده , , Vicki L. Coffin، نويسنده , , Kathleen A. Cox، نويسنده , , Diane E. Grotz، نويسنده , , Ruth A. Duffy، نويسنده , , et al، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2001
Pages
4
From page
2311
To page
2314
Abstract
The potential toxicological liabilities of the M2 muscarinic antagonist 1 were addressed by replacing the methylenedioxyphenyl moiety with a p-methoxyphenyl group, resulting in M2 selective compounds such as 3. Several halogenated naphthamide derivatives of 3 were studied in order to improve the pharmacokinetic profile via blockage of oxidative metabolism. Compound 4 demonstrated excellent M2 affinity and selectivity, human microsomal stability, and oral bioavailability in rodents and primates.
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2001
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
791622
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