1. Discovery of novel potent imidazo[1,2-b]pyridazine PDE10a inhibitors
- Author
-
Raymond J. Patch, Tianbao Lu, Hui Huang, Brian Rady, Alan Gibbs, Thomas Kirchner, Yu-Kai Lee, Carl R. Illig, Parks Daniel J, Margery A. Connelly, Sanath K. Meegalla, Mark R. Player, Wing S. Cheung, Chen Jinsheng, John G. Geisler, Hossein B. Askari, Kenneth J. Wilson, and Sharmila Patel
- Subjects
Phosphodiesterase Inhibitors ,Pyridines ,medicine.medical_treatment ,Clinical Biochemistry ,Pharmaceutical Science ,Pharmacology ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Rats, Sprague-Dawley ,Pyridazine ,Structure-Activity Relationship ,chemistry.chemical_compound ,Pharmacokinetics ,In vivo ,Drug Discovery ,medicine ,Animals ,Humans ,Insulin ,Molecular Biology ,G protein-coupled receptor ,Binding Sites ,Phosphoric Diester Hydrolases ,010405 organic chemistry ,Organic Chemistry ,Imidazoles ,Glucose Tolerance Test ,In vitro ,Protein Structure, Tertiary ,Rats ,0104 chemical sciences ,Molecular Docking Simulation ,chemistry ,Drug Design ,Molecular Medicine ,Secretagogue ,PDE10A ,Half-Life ,Protein Binding - Abstract
Design and optimization of a novel series of imidazo[1,2-b]pyridazine PDE10a inhibitors are described. Compound 31 displays excellent pharmacokinetic properties and was also evaluated as an insulin secretagogue in vitro and in vivo.
- Published
- 2016