The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: the second clinical candidate having a shorter and favorable human half-life

JL Wang, D Limburg, MJ Graneto, J Springer…

Index: Wang, Jane L.; Limburg, David; Graneto, Matthew J.; Springer, John; Hamper, Joseph Rogier Bruce; Liao, Subo; Pawlitz, Jennifer L.; Kurumbail, Ravi G.; Maziasz, Timothy; Talley, John J.; Kiefer, James R.; Carter, Jeffery Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 23 p. 7159 - 7163

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Citation Number: 81

Abstract

In this Letter, we provide the structure–activity relationships, optimization of design, testing criteria, and human half-life data for a series of selective COX-2 inhibitors. During the course of our structure-based drug design efforts, we discovered two distinct binding modes within the COX-2 active site for differently substituted members of this class. The challenge of a undesirably long human half-life for the first clinical candidate 1t1/2= 360h was addressed ...