title: Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists.
abstract: We described here the synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as potential mGluR5 antagonists. We found that a series of thiazole derivatives 6 showed better inhibitory activity against mGluR5. Compounds 6bc and 6bj have been identified as potent antagonists (IC50=274 and 159nM) showing excellent in vitro stability profile. Molecular docking study using the crystal structure of mGluR5 revealed that our compounds 6bc and 6bj fit the allosteric binding site of mavoglurant well.
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; Department of Biological Chemistry, Korea University of Science and Technology (UST), 217 Gajungro, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Hoang Nam
authors.initials: HN
authors.lastname: Vu
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; Department of Biological Chemistry, Korea University of Science and Technology (UST), 217 Gajungro, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Ahmed H E
authors.initials: AH
authors.lastname: Hassan
authors.affiliation: Department of Chemistry, Korea University, Seoul 02841, Republic of Korea.
authors.forename: Kihang
authors.initials: K
authors.lastname: Choi
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea.
authors.forename: Jong-Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; Department of Biological Chemistry, Korea University of Science and Technology (UST), 217 Gajungro, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Ki Duk
authors.initials: KD
authors.lastname: Park
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; Department of Biological Chemistry, Korea University of Science and Technology (UST), 217 Gajungro, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Jae Kyun
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; Department of Biological Chemistry, Korea University of Science and Technology (UST), 217 Gajungro, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Ae Nim
authors.initials: AN
authors.lastname: Pae
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; Department of Biological Chemistry, Korea University of Science and Technology (UST), 217 Gajungro, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Hyunah
authors.initials: H
authors.lastname: Choo
authors.affiliation: Department of Applied Chemistry, Hanyang University, Ansan, Gyeonggi-do 15588, Republic of Korea. Electronic address: sjmin@hanyang.ac.kr.
authors.forename: Sun-Joon
authors.initials: SJ
authors.lastname: Min
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST), 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; Department of Biological Chemistry, Korea University of Science and Technology (UST), 217 Gajungro, Yuseong-gu, Daejeon 34113, Republic of Korea. Electronic address: ys4049@kist.re.kr.
authors.forename: Yong Seo
authors.initials: YS
authors.lastname: Cho
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010848:Picolinic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000577:Amides; C578935:GRM5 protein, human; D010848:Picolinic Acids; D064529:Receptor, Metabotropic Glutamate 5; D013844:Thiazoles; C003142:picolinamide
keywords: Antagonist; Metabotropic glutamate receptor; Molecular docking; Picolinamides; Thiazole-2-carboxamides