Pyrazole-based sulfonamide and sulfamides as potent inhibitors of mammalian 15-lipoxygenase

Khehyong Ngu; David S Weinstein; Wen Liu; Charles Langevine; Donald W Combs; Shaobin Zhuang; Xing Chen; Cort S Madsen; Timothy W Harper; Saleem Ahmad; Jeffrey A Robl

doi:10.1016/j.bmcl.2011.05.107

Pyrazole-based sulfonamide and sulfamides as potent inhibitors of mammalian 15-lipoxygenase

Bioorg Med Chem Lett. 2011 Jul 15;21(14):4141-5. doi: 10.1016/j.bmcl.2011.05.107. Epub 2011 Jun 6.

Authors

Khehyong Ngu¹, David S Weinstein, Wen Liu, Charles Langevine, Donald W Combs, Shaobin Zhuang, Xing Chen, Cort S Madsen, Timothy W Harper, Saleem Ahmad, Jeffrey A Robl

Affiliation

¹ Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543, USA. khehyong.ngu@bms.com

PMID: 21696952
DOI: 10.1016/j.bmcl.2011.05.107

Abstract

A series of inhibitors of mammalian 15-lipoxygenase (15-LO) based on a 3,4,5-tri-substituted pyrazole scaffold is described. Replacement of a sulfonamide functionality in the lead series with a sulfamide group resulted in improved physicochemical properties generating analogs with enhanced inhibition in cell-based and whole blood assays.

MeSH terms

Amides / chemical synthesis
Amides / chemistry*
Amides / pharmacology
Animals
Arachidonate 15-Lipoxygenase / chemistry*
Arachidonate 15-Lipoxygenase / metabolism
CHO Cells
Cricetinae
Cricetulus
Humans
Hydroxyeicosatetraenoic Acids / blood
Lipoxygenase Inhibitors / chemical synthesis
Lipoxygenase Inhibitors / chemistry*
Lipoxygenase Inhibitors / pharmacology
Pyrazoles / chemistry*
Rabbits
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry
Sulfonamides / pharmacology

Substances

Amides
Hydroxyeicosatetraenoic Acids
Lipoxygenase Inhibitors
Pyrazoles
Sulfonamides
pyrazole
15-hydroxy-5,8,11,13-eicosatetraenoic acid
Arachidonate 15-Lipoxygenase