Discovery of CP-199,330 and CP-199,331: two potent and orally efficacious cysteinyl LT1 receptor antagonists devoid of liver toxicity.
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).
Chambers
R J
RJ
Central Research Division, Pfizer Inc., Groton, CT 06340, USA.
Marfat
A
A
Antognoli
G W
GW
Cheng
J B
JB
Damon
D B
DB
Kuperman
A V
AV
Liston
T C
TC
Mebus
C
C
Pillar
J S
JS
Shirley
J T
JT
Watson
J W
JW
D000818:Animals; D001578:Benzopyrans / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D015195:Drug Design; D006168:Guinea Pigs; D006207:Half-Life; D000882:Haplorhini; D020024:Leukotriene Antagonists; D008099:Liver / Q000187:drug effects*; D008565:Membrane Proteins; D051381:Rats; D018077:Receptors, Leukotriene; D013449:Sulfonamides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*
D001578:Benzopyrans; C122099:CP 199331; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D018077:Receptors, Leukotriene; D013449:Sulfonamides; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor; C122098:CP 199330