Identification of (R)-6-(1-(4-Cyano-3-methylphenyl)-5-cyclopentyl-4, 5-dihydro-1 H-pyrazol-3-yl)-2-methoxynicotinic Acid, a Highly Potent and Selective Nonsteroidal …

A Casimiro-Garcia, DW Piotrowski…

Index: Casimiro-Garcia, Agustin; Piotrowski, David W.; Ambler, Catherine; Arhancet, Graciela B.; Banker, Mary Ellen; Banks, Tereece; Boustany-Kari, Carine M.; Cai, Cuiman; Chen, Xiangyang; Eudy, Rena; Hepworth, David; Hulford, Catherine A.; Jennings, Sandra M.; Loria, Paula M.; Meyers, Marvin J.; Petersen, Donna N.; Raheja, Neil K.; Sammons, Matthew; She, Li; Song, Kun; Vrieze, Derek; Wei, Liuqing Journal of Medicinal Chemistry, 2014 , vol. 57, # 10 p. 4273 - 4288

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Citation Number: 8

Abstract

A novel series of nonsteroidal mineralocorticoid receptor (MR) antagonists identified as part of our strategy to follow up on the clinical candidate PF-03882845 (2) is reported. Optimization departed from the previously described pyrazoline 3a and focused on improving the selectivity for MR versus the progesterone receptor (PR) as an approach to avoid potential sex-hormone-related adverse effects and improving biopharmaceutical ...