A thienopyridazinone-based melanin-concentrating hormone receptor 1 antagonist with potent in vivo anorectic properties.

作者信息

Dyck Brian, Markison Stacy, Zhao Liren, Tamiya Junko, Grey Jonathan, Rowbottom Martin W, Zhang Mingzhu, Vickers Troy, Sorensen Katie, Norton Christi, Wen Jenny, Heise Christopher E, Saunders John, Conlon Paul, Madan Ajay, Schwarz David, Goodfellow Val S

机构信息

Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, California 92130, USA.

出版信息

J Med Chem. 2006 Jun 29;49(13):3753-6. doi: 10.1021/jm051263c.

Melanin-concentrating hormone receptor antagonists containing thieno- and a benzopyridazinone cores were designed and tested as potential anorectic agents. These ligands showed high affinity for the receptor, potent functional activity in vitro, and good oral bioavailabilty in rats. The thiophene analogue exhibited low iv clearance, long half-life, and high brain penetration. In obese rats, the thienopyridazinone demonstrated a dose-dependent reduction in feeding and body weight with doses between 1 and 10 mg kg-1.