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Bioorg Med Chem Lett. 2012 Feb 15;22(4):1550-6. doi: 10.1016/j.bmcl.2012.01.002. Epub 2012 Jan 10.

Discovery of benzodihydroisofurans as novel, potent, bioavailable and brain-penetrant prolylcarboxypeptidase inhibitors.

Author information

1
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA. hongshen@stanfordalumni.org

Abstract

A series of benzodihydroisofurans were discovered as novel, potent, bioavailable and brain-penetrant prolylcarboxypeptidase (PrCP) inhibitors. The structure-activity relationship (SAR) is focused on improving PrCP activity and metabolic stability, and reducing plasma protein binding. In the established diet-induced obese (eDIO) mouse model, compound ent-3a displayed target engagement both in plasma and in brain. However, this compound failed to induce significant body weight loss in eDIO mice in a five-day study.

PMID:
22264488
DOI:
10.1016/j.bmcl.2012.01.002
[Indexed for MEDLINE]

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