| Title : The discovery of non-benzimidazole and brain-penetrant prolylcarboxypeptidase inhibitors - Graham_2012_Bioorg.Med.Chem.Lett_22_658 |
| Author(s) : 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 |
| Ref : Bioorganic & Medicinal Chemistry Lett , 22 :658 , 2012 |
|
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. |
| PubMedSearch : Graham_2012_Bioorg.Med.Chem.Lett_22_658 |
| PubMedID: 22079761 |
| Gene_locus related to this paper: human-PRCP |
| Inhibitor | CHEMBL1938516 CHEMBL1684295 |
| Gene_locus | human-PRCP |
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 (2012)
The discovery of non-benzimidazole and brain-penetrant prolylcarboxypeptidase inhibitors
Bioorganic & Medicinal Chemistry Lett
22 :658
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 (2012)
Bioorganic & Medicinal Chemistry Lett
22 :658