title: Discovery of biological evaluation of pyrazole/imidazole amides as mGlu5 receptor negative allosteric modulators.
abstract: Development of SAR in a 5-aryl-3-acylpyridinyl-pyrazoles and 1-aryl-4-acylpyridinyl imidazoles series of mGlu5 receptor negative allosteric modulators (mGluR5 NAMs) using a functional cell-based assay is described in this Letter. Analysis of the Ligand-lipophilic efficiency (LipE) of compounds provided new insight for the design of potent mGluR5 negative allosteric modulators with anti-depressant activities.
authors: CNS Drug Discovery, Drug Development Center, SK Biopharmaceuticals, Daejeon 305-712, Republic of Korea. Eunhee.chae@sk.com
authors: Eunhee
authors: E
authors: Chae
authors: Yong-Je
authors: YJ
authors: Shin
authors: Eun-Ju
authors: EJ
authors: Ryu
authors: Mi Kyung
authors: MK
authors: Ji
authors: Nahm
authors: N
authors: Ryune Cho
authors: Ki-Ho
authors: KH
authors: Lee
authors: Hyun Ji
authors: HJ
authors: Jeong
authors: Soo-Jin
authors: SJ
authors: Kim
authors: Yeonjung
authors: Y
authors: Choi
authors: Kyung
authors: K
authors: Seok Oh
authors: Chun-Eung
authors: CE
authors: Park
authors: Young
authors: Y
authors: Soo Yoon
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D057809:HEK293 Cells; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; C578935:GRM5 protein, human; C578936:Grm5 protein, mouse; C578937:Grm5 protein, rat; D007093:Imidazoles; D008024:Ligands; D011720:Pyrazoles; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C031280:pyrazole