The novel benzopyran class of selective cyclooxygenase-2 inhibitors-part I: The first clinical candidate

In this manuscript, we report the discovery of the substituted 2-trifluoromethyl-2H-benzopyran-3-carboxylic acids as a novel series of potent and selective cyclooxygenase-2 (COX-2) inhibitors. 5c-(S) (SD-8381) was advanced into clinical studies due to its superior in vivo potency. The high plasma protein binding (>99% bound) of 5c-(S) has resulted in a surprisingly long human half life t1/2 = 360 h.

Graphical abstractThe design and synthesis of a series of potent and selective COX-2 inhibitors based on a benzopyran lead (1) is described. Our SAR studies allowed us to optimize this series resulting in the identification of clinical compound 5c-(S), which possesses superior in vivo efficacy in animal models of inflammation and pain.Figure optionsDownload full-size imageDownload as PowerPoint slide