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 t(1/2)=360 h.
Pfizer Global Research and Development, Chesterfield, MO 63017, USA. jl47wang@yahoo.com
Jane L
JL
Wang
Jeffery
J
Carter
James R
JR
Kiefer
Ravi G
RG
Kurumbail
Jennifer L
JL
Pawlitz
David
D
Brown
Susan J
SJ
Hartmann
Matthew J
MJ
Graneto
Karen
K
Seibert
John J
JJ
Talley
D001578:Benzopyrans / Q000737:chemistry* / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism; D002264:Carboxylic Acids; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D011485:Protein Binding; D013329:Structure-Activity Relationship
D001578:Benzopyrans; D001798:Blood Proteins; D002264:Carboxylic Acids; D052246:Cyclooxygenase 2 Inhibitors