N-carbamoyl analogs of Zafirlukast: potent receptor antagonists of leukotriene D4.
Exploration of the indole nitrogen region of Zafirlukast (1) has uncovered a potent series of cysteinyl leukotriene D4 (LTD4) antagonists. These studies showed that a variety of functionality could be incorporated in this region of the molecule without sacrificing potency. Efforts to exploit this site in order to improve oral efficacy are discussed.
Brown
M F
MF
Pfizer Central Research, Groton, CT 06340, USA.
Marfat
A
A
Antognoli
G
G
Chambers
R J
RJ
Cheng
J B
JB
Damon
D B
DB
Liston
T E
TE
McGlynn
M A
MA
O'Sullivan
S P
SP
Owens
B S
BS
Pillar
J S
JS
Shirley
J T
JT
Watson
J W
JW
D000818:Animals; D006168:Guinea Pigs; D000882:Haplorhini; D006801:Humans; D007211:Indoles; D020024:Leukotriene Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D008565:Membrane Proteins; D008956:Models, Chemical; D048448:Phenylcarbamates; D051381:Rats; D018077:Receptors, Leukotriene; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000737:chemistry* / Q000494:pharmacology
D007211:Indoles; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D048448:Phenylcarbamates; D018077:Receptors, Leukotriene; D013449:Sulfonamides; D014105:Tosyl Compounds; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor; C062735:zafirlukast