Design and Discovery of a Selective Small Molecule κ Opioid Antagonist (2-Methyl-N-((2′-(pyrrolidin-1-ylsulfonyl) biphenyl-4-yl) methyl) propan-1-amine, PF- …

…, M Vanase-Frawley, J Freeman…

Index: Verhoest, Patrick R.; Sawant Basak, Aarti; Parikh, Vinod; Hayward, Matthew; Kauffman, Gregory W.; Paradis, Vanessa; McHardy, Stanton F.; McLean, Stafford; Grimwood, Sarah; Schmidt, Anne W.; Vanase-Frawley, Michelle; Freeman, Jodi; Van Deusen, Jeffrey; Cox, Loretta; Wong, Diane; Liras, Spiros Journal of Medicinal Chemistry, 2011 , vol. 54, # 16 p. 5868 - 5877

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Citation Number: 21

Abstract

By use of parallel chemistry coupled with physicochemical property design, a series of selective κ opioid antagonists have been discovered. The parallel chemistry strategy utilized key monomer building blocks to rapidly expand the desired SAR space. The potency and selectivity of the in vitro κ antagonism were confirmed in the tail-flick analgesia model. This model was used to build an exposure–response relationship between the κ K i and the ...