Melanin concentrating hormone receptor 1 (MCHR1) antagonists - Still a viable approach for obesity treatment?

TY - JOUR

T1 - Melanin concentrating hormone receptor 1 (MCHR1) antagonists - Still a viable approach for obesity treatment?

AU - Högberg, T.

AU - Frimurer, T.M.

AU - Sasmal, P.K.

PY - 2012/10/1

Y1 - 2012/10/1

N2 - Obesity is a global epidemic associated with multiple severe diseases. Several pharmacotherapies have been investigated including the melanin concentrating hormone (MCH) and its receptor 1. The development of MCHR1 antagonists are described with a specific perspective on different chemotypes investigated in efforts to overcome hERG liabilities while having orally active, potent and selective compounds with sufficient brain penetration. A chemometric comparison of ∼2000 diverse MCHR1 and ∼1000 diverse hERG ligands underline the structural similarities. A binding pocket analysis of a MCHR1 model and recent X-ray structures of GPCRs invoked in selectivity issues indicate a way to support future drug design.

AB - Obesity is a global epidemic associated with multiple severe diseases. Several pharmacotherapies have been investigated including the melanin concentrating hormone (MCH) and its receptor 1. The development of MCHR1 antagonists are described with a specific perspective on different chemotypes investigated in efforts to overcome hERG liabilities while having orally active, potent and selective compounds with sufficient brain penetration. A chemometric comparison of ∼2000 diverse MCHR1 and ∼1000 diverse hERG ligands underline the structural similarities. A binding pocket analysis of a MCHR1 model and recent X-ray structures of GPCRs invoked in selectivity issues indicate a way to support future drug design.

UR - http://www.scopus.com/inward/record.url?scp=84866384546&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2012.08.025

DO - 10.1016/j.bmcl.2012.08.025

M3 - Journal article

AN - SCOPUS:84866384546

SN - 0960-894X

VL - 22

SP - 6039

EP - 6047

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 19

ER -