Terphenyl cyclooxygenase-2 (COX-2) inhibitors: optimization of the central ring and o-biphenyl analogs

D J Pinto; D G Batt; W J Pitts; J J Petraitis; M J Orwat; S Wang; J W Jetter; S R Sherk; G C Houghton; R A Copeland; M B Covington; J M Trzaskos; R L Magolda

doi:10.1016/s0960-894x(99)00105-5

Terphenyl cyclooxygenase-2 (COX-2) inhibitors: optimization of the central ring and o-biphenyl analogs

Bioorg Med Chem Lett. 1999 Apr 5;9(7):919-24. doi: 10.1016/s0960-894x(99)00105-5.

Authors

D J Pinto¹, D G Batt, W J Pitts, J J Petraitis, M J Orwat, S Wang, J W Jetter, S R Sherk, G C Houghton, R A Copeland, M B Covington, J M Trzaskos, R L Magolda

Affiliation

¹ The DuPont Pharmaceutical Company, Wilmington, DE 19880-0500, USA.

PMID: 10230611
DOI: 10.1016/s0960-894x(99)00105-5

Abstract

The discovery of terphenyl derivatives as highly selective COX-2 inhibitors resulted from our efforts to overcome poor pharmacokinetics demonstrated by the COX-2 selective diarylthiophene DuP 697 [2-bromo-4-(4'-sulfonylmethyl)phenyl-5-(4'-fluoro)phenylthiophe ne]. Detailed SAR related to the ortho-biphenyls and variants of the central ring are described herein.

MeSH terms

Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / chemistry*
Cyclooxygenase Inhibitors / pharmacokinetics
Isoenzymes / drug effects
Molecular Structure
Prostaglandin-Endoperoxide Synthases / drug effects
Structure-Activity Relationship
Thiophenes / pharmacokinetics

Substances

Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Isoenzymes
Thiophenes
DuP 697
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases