PF-06273340 / Pfizer - LARVOL DELTA

Discovery of Potent, Selective and Peripherally Restricted Pan-Trk Kinase Inhibitors for the Treatment of Pain. (PubMed, J Med Chem) - "Moreover, inhibition of the TrkA kinase pathway in pain has been clinically validated by the NGF antibody tanezumab, leading to significant interest in the development of small molecule inhibitors of TrkA. Herein we discuss the discovery of two potent, selective, peripherally restricted, efficacious and well-tolerated series of pan-Trk inhibitors which successfully delivered three candidate quality compounds 10b, 13b and 19. All three compounds are predicted to possess low metabolic clearance in human that does not proceed via aldehyde oxidase-catalyzed reactions, thus addressing the potential clearance prediction liability associated with our current pan-Trk development candidate PF-06273340."

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