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Key stages in the hit to lead pathway of DSM265. Replacement of the second phenyl ring in the naphthyl group with a trifluoromethyl group improved solubility. Addition of a 1,1-difluoroethyl group significantly increased the potency and final replacement of the trifluoromethyl group in D′2 with a pentafluorosulfur moiety led to the optimized compound DSM265
