Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2012 Jan 1;22(1):658-65. doi: 10.1016/j.bmcl.2011.10.060. Epub 2011 Oct 24.

The discovery of non-benzimidazole and brain-penetrant prolylcarboxypeptidase inhibitors.

Author information

1
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. thomas.graham@merck.com

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.

PMID:
22079761
DOI:
10.1016/j.bmcl.2011.10.060
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center