Rational design of a novel peripherally-restricted, orally active CB1 cannabinoid antagonist containing a 2,3-diarylpyrrole motif

A rational design approach around a new pyrrole core with modulation of the topological polar surface area allowed the identification of the potent, selective and peripherally-restricted CB1 antagonist 11 [X = -(CH2)3NHSO2Me; R = (4,4-difluoropiperidyl)] with a IC50 (hCB1) = 1.4 nM.