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- …
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 ...
