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Bioorg Med Chem Lett. 2009 May 1;19(9):2400-3. doi: 10.1016/j.bmcl.2009.03.082. Epub 2009 Mar 25.

Synthesis and SAR of 1,2,3,4-tetrahydroisoquinolin-1-ones as novel G-protein-coupled receptor 40 (GPR40) antagonists.

Author information

1
Pfizer Global R&D, Eastern Point Road, Groton, CT 06340, USA.

Abstract

The development of a series of novel 1,2,3,4-tetrahydroisoquinolin-1-ones as antagonists of G protein-coupled receptor 40 (GPR40) is described. The synthesis, in vitro inhibitory values for GPR40, in vitro microsomal clearance and rat in vivo clearance data are discussed. Initial hits displayed high rat in vivo clearances that were higher than liver blood flow. Optimization of rat in vivo clearance was achieved and led to the identification of 15i, whose rat oral pharmacokinetic data is reported.

PMID:
19346127
DOI:
10.1016/j.bmcl.2009.03.082
[Indexed for MEDLINE]

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