Identification of metabolites of the tryptase inhibitor CRA-9249: Observation of a metabolite derived from an unexpected hydroxylation pathway

…, T Mahajan, C O'Brian, EJ Shelton, D Sperandio…

Index: Yu, Walter; Dener, Jeffrey M.; Dickman, Daniel A.; Grothaus, Paul; Ling, Yun; Liu, Liang; Havel, Chris; Malesky, Kimberly; Mahajan, Tania; O'Brian, Colin; Shelton, Emma J.; Sperandio, David; Tong, Zhiwei; Yee, Robert; Mordenti, Joyce J. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 15 p. 4053 - 4058

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Citation Number: 2

Abstract

The metabolites of the tryptase inhibitor CRA-9249 were identified after exposure to liver microsomes. CRA-9249 was found to be degraded rapidly in liver microsomes from rabbit, dog, cynomolgus monkey, and human, and less rapidly in microsomes from rat. The key metabolites included cleavage of an aryl ether, in addition to an unexpected hydroxylation of the amide side chain adjacent to the amide nitrogen. The chemical structures of both ...