Discovery of CP-199,330 and CP-199,331: two potent and orally efficacious cysteinyl LT1 receptor antagonists devoid of liver toxicity

R J Chambers; A Marfat; G W Antognoli; J B Cheng; D B Damon; A V Kuperman; T C Liston; C Mebus; J S Pillar; J T Shirley; J W Watson

doi:10.1016/s0960-894x(99)00461-8

Discovery of CP-199,330 and CP-199,331: two potent and orally efficacious cysteinyl LT1 receptor antagonists devoid of liver toxicity

Bioorg Med Chem Lett. 1999 Sep 20;9(18):2773-8. doi: 10.1016/s0960-894x(99)00461-8.

Authors

R J Chambers¹, A Marfat, G W Antognoli, J B Cheng, D B Damon, A V Kuperman, T C Liston, C Mebus, J S Pillar, J T Shirley, J W Watson

Affiliation

¹ Central Research Division, Pfizer Inc., Groton, CT 06340, USA.

PMID: 10509933
DOI: 10.1016/s0960-894x(99)00461-8

Abstract

CP-199,330 (3) and CP-199,331 (4) are cysLT1 receptor antagonists that are equipotent to marketed cysLT1 receptor antagonists zafirlukast and pranlukast, show good pharmacokinetics in rats and monkeys, and are devoid of liver toxicity in monkeys as seen in CP-85,958 (1).

MeSH terms

Animals
Benzopyrans / adverse effects
Benzopyrans / pharmacokinetics
Benzopyrans / pharmacology*
Biological Availability
Drug Design
Guinea Pigs
Half-Life
Haplorhini
Leukotriene Antagonists*
Liver / drug effects*
Membrane Proteins*
Rats
Receptors, Leukotriene*
Sulfonamides / adverse effects
Sulfonamides / pharmacokinetics
Sulfonamides / pharmacology*

Substances

Benzopyrans
CP 199331
Leukotriene Antagonists
Membrane Proteins
Receptors, Leukotriene
Sulfonamides
cysteinyl leukotriene receptor 2
leukotriene D4 receptor
CP 199330