Design and synthesis of aryl sulfonamide-based nonsteroidal mineralocorticoid receptor antagonists

Kentaro Futatsugi; David W Piotrowski; Agustin Casimiro-Garcia; Shaughn Robinson; Matthew Sammons; Paula M Loria; Mary E Banker; Donna N Petersen; Natalia J Schmidt

doi:10.1016/j.bmcl.2013.09.099

Design and synthesis of aryl sulfonamide-based nonsteroidal mineralocorticoid receptor antagonists

Bioorg Med Chem Lett. 2013 Dec 1;23(23):6239-42. doi: 10.1016/j.bmcl.2013.09.099. Epub 2013 Oct 8.

Authors

Kentaro Futatsugi¹, David W Piotrowski, Agustin Casimiro-Garcia, Shaughn Robinson, Matthew Sammons, Paula M Loria, Mary E Banker, Donna N Petersen, Natalia J Schmidt

Affiliation

¹ Pfizer Worldwide Research and Development, 620 Memorial Drive, Cambridge, MA 02139, United States. Electronic address: Kentaro.Futatsugi@pfizer.com.

PMID: 24157365
DOI: 10.1016/j.bmcl.2013.09.099

Abstract

Hit-to-lead medicinal chemistry efforts are described starting from a screening hit 1, leading to a new class of aryl sulfonamide-based MR antagonist, exemplified by 17, that possesses favourable MR binding affinity, selectivity profile against closely related NHRs, physicochemical properties and metabolic stability.

Keywords: Aryl sulfonamide; Mineralocorticoid receptor; Nonsteroidal MR antagonist.

MeSH terms

Humans
Mineralocorticoid Receptor Antagonists / chemical synthesis
Mineralocorticoid Receptor Antagonists / chemistry*
Mineralocorticoid Receptor Antagonists / pharmacology*
Models, Molecular
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry*
Sulfonamides / pharmacology*

Substances

Mineralocorticoid Receptor Antagonists
Sulfonamides