title: Synthesis and SAR studies of bicyclic amine series GPR119 agonists.
abstract: We disclosed a novel series of G-protein coupled receptor 119 (GPR119) agonists based on a bicyclic amine scaffold. Through the optimization of hit compound 1, we discovered that the basic nitrogen atom of bicyclic amine played an important role in GPR119 agonist activity expression and that an indanone in various bicyclic rings was suitable in this series of compounds. The indanone derivative 2 showed the effect of plasma glucose control in oGTT and scGTT in the rodent model.
authors: Drug Discovery Laboratories, Sanwa Kagaku Kenkyusho Co., Ltd, Hokusei-cho, Inabe-shi Mie, Japan. m_sakairi@skk-net.com
authors: Masao
authors: M
authors: Sakairi
authors: Masakazu
authors: M
authors: Kogami
authors: Masafumi
authors: M
authors: Torii
authors: Hiroyo
authors: H
authors: Kataoka
authors: Hiroki
authors: H
authors: Fujieda
authors: Mitsuhiro
authors: M
authors: Makino
authors: Daisuke
authors: D
authors: Kataoka
authors: Ryuji
authors: R
authors: Okamoto
authors: Toshiyuki
authors: T
authors: Miyazawa
authors: Morio
authors: M
authors: Okabe
authors: Megumi
authors: M
authors: Inoue
authors: Naoki
authors: N
authors: Takahashi
authors: Satoko
authors: S
authors: Harada
authors: Nobuhide
authors: N
authors: Watanabe
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007189:Indans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D001786:Blood Glucose; D001643:Bridged Bicyclo Compounds; C519854:GPR119 protein, human; D007004:Hypoglycemic Agents; D007189:Indans; D011743:Pyrimidines; D043562:Receptors, G-Protein-Coupled; C013352:indacrinone