title: Discovery of 2H-Chromen-2-one Derivatives as G Protein-Coupled Receptor-35 Agonists.
abstract: A family of 2H-chromen-2-one derivatives were identified as G protein-coupled receptor-35 (GPR35) agonists using dynamic mass redistribution assays in HT-29 cells. The compounds with 1H-tetrazol-5-yl in 3-substituted position displayed higher potency than the corresponding carboxyl analogs, and the hydroxyl group in the 7-position also played an important role in GPR35 agonistic activity. 6-Bromo-7-hydroxy-8-nitro-3-(1H-tetrazol-5-yl)-2H-chromen-2-one (50) was found to be the most potent GPR35 agonist with an EC50of 5.8 nM. Calculating the physicochemical properties of compounds with moderate to high potency suggested that compounds 30, 50, and 51 showed good druggability. This study provides a novel series of GPR35 agonists, and compound 50 may be a powerful tool to study GPR35.
authors.affiliation: Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, China.
authors.forename: Jixia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, China.|Co-innovation Center of Neuroregeneration, Nantong University , Nantong 226019, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, China.
authors.forename: Yaopeng
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Hou
authors.affiliation: Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, China.
authors.forename: Lala
authors.initials: L
authors.lastname: Qu
authors.affiliation: Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Shi
authors.affiliation: Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023, China.|Co-innovation Center of Neuroregeneration, Nantong University , Nantong 226019, China.
authors.forename: Xinmiao
authors.identifier: 0000-0001-5802-1961
authors.initials: X
authors.lastname: Liang
authors.affiliation: Biochemical Technologies, Science and Technology Division, Corning , New York 14831, United States.
authors.forename: Ye
authors.initials: Y
authors.lastname: Fang
mesh_terms: D001578:Benzopyrans / Q000737:chemistry* / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D019073:HT29 Cells; D006801:Humans; D013058:Mass Spectrometry; D066244:Proton Magnetic Resonance Spectroscopy; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*
chemical_list: D001578:Benzopyrans; C111379:GPR35 protein, human; D043562:Receptors, G-Protein-Coupled