N-carbamoyl analogs of Zafirlukast: potent receptor antagonists of leukotriene D4

M F Brown; A Marfat; G Antognoli; R J Chambers; J B Cheng; D B Damon; T E Liston; M A McGlynn; S P O'Sullivan; B S Owens; J S Pillar; J T Shirley; J W Watson

doi:10.1016/s0960-894x(98)00442-9

N-carbamoyl analogs of Zafirlukast: potent receptor antagonists of leukotriene D4

Bioorg Med Chem Lett. 1998 Sep 22;8(18):2451-6. doi: 10.1016/s0960-894x(98)00442-9.

Authors

M F Brown¹, A Marfat, G Antognoli, R J Chambers, J B Cheng, D B Damon, T E Liston, M A McGlynn, S P O'Sullivan, B S Owens, J S Pillar, J T Shirley, J W Watson

Affiliation

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

PMID: 9873560
DOI: 10.1016/s0960-894x(98)00442-9

Abstract

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.

MeSH terms

Animals
Guinea Pigs
Haplorhini
Humans
Indoles
Leukotriene Antagonists* / chemical synthesis*
Leukotriene Antagonists* / pharmacology*
Membrane Proteins*
Models, Chemical
Phenylcarbamates
Rats
Receptors, Leukotriene*
Sulfonamides
Tosyl Compounds / chemistry*
Tosyl Compounds / pharmacology

Substances

Indoles
Leukotriene Antagonists
Membrane Proteins
Phenylcarbamates
Receptors, Leukotriene
Sulfonamides
Tosyl Compounds
cysteinyl leukotriene receptor 2
leukotriene D4 receptor
zafirlukast