Abstract
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.
| Original language | English |
|---|---|
| Journal | Bioorganic & Medicinal Chemistry Letters |
| Volume | 22 |
| Issue number | 19 |
| Pages (from-to) | 6039-6047 |
| Number of pages | 9 |
| ISSN | 0960-894X |
| DOIs | |
| Publication status | Published - 1 Oct 2012 |
