title: Discovery of novel potent imidazo[1,2-b]pyridazine PDE10a inhibitors.
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.
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Sanath K
authors: SK
authors: Meegalla
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Hui
authors: H
authors: Huang
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Carl R
authors: CR
authors: Illig
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Daniel J
authors: DJ
authors: Parks
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Jinsheng
authors: J
authors: Chen
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Yu-Kai
authors: YK
authors: Lee
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Kenneth J
authors: KJ
authors: Wilson
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Sharmila K
authors: SK
authors: Patel
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Wing S
authors: WS
authors: Cheung
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Tianbao
authors: T
authors: Lu
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Thomas
authors: T
authors: Kirchner
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Hossein B
authors: HB
authors: Askari
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: John
authors: J
authors: Geisler
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Raymond J
authors: RJ
authors: Patch
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Alan C
authors: AC
authors: Gibbs
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Brian
authors: B
authors: Rady
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.
authors: Margery
authors: M
authors: Connelly
authors: Janssen Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA. Electronic address: mplayer@its.jnj.com.
authors: Mark R
authors: MR
authors: Player
mesh_terms: D000818:Animals; D001665:Binding Sites; D015195:Drug Design; D005951:Glucose Tolerance Test; D006207:Half-Life; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D007328:Insulin / Q000378:metabolism; D062105:Molecular Docking Simulation; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D007328:Insulin; D010726:Phosphodiesterase Inhibitors; D011725:Pyridines; C000619660:imidazopyridine; C119843:PDE10A protein, human; D010727:Phosphoric Diester Hydrolases
keywords: Brain penetration; GPCR; GSIS; Insulin secretagogues; PDE10a inhibitor; Type 2 diabetes