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ID: ALA1938250
Journal: Bioorg Med Chem Lett
Title: The discovery of non-benzimidazole and brain-penetrant prolylcarboxypeptidase inhibitors.
Authors: Graham TH, Shen HC, Liu W, Xiong Y, Verras A, Bleasby K, Bhatt UR, Chabin RM, Chen D, Chen Q, Garcia-Calvo M, Geissler WM, He H, Lassman ME, Shen Z, Tong X, Tung EC, Xie D, Xu S, Colletti SL, Tata JR, Hale JJ, Pinto S, Shen DM.
Abstract: Novel prolylcarboxypeptidase (PrCP) inhibitors with nanomolar IC(50) values were prepared by replacing the previously described dichlorobenzimidazole-substituted pyrrolidine amides with a variety of substituted benzylamine amides. In contrast to prior series, the compounds demonstrated minimal inhibition shift in whole serum and minimal recognition by P-glycoprotein (P-gp) efflux transporters. The compounds were also cell permeable and demonstrated in vivo brain exposure. The in vivo effect of compound (S)-6e on weight loss in an established diet-induced obesity (eDIO) mouse model was studied.
CiteXplore: 22079761