title: Thieno[3,2-b]thiophene-2-carboxylic acid derivatives as GPR35 agonists.
abstract: The optimization of a series of thieno[3,2-b]thiophene-2-carboxylic acid derivatives for agonist activity against the GPR35 is reported. Compounds were optimized to achieve β-arrestin-biased agonism for developing probe molecules that may be useful for elucidating the biology and physiology of GPR35. Compound 13 was identified to the most potent GPR35 agonist, and compounds 30 and 36 exhibited the highest efficacy to cause β-arrestin translocation.
authors.affiliation: Biochemical Technologies, Science and Technology Division, Corning Inc., Corning, NY 14831, USA.
authors.forename: Huayun
authors.initials: H
authors.lastname: Deng
authors.forename: Jieyu
authors.initials: J
authors.lastname: Hu
authors.forename: Haibei
authors.initials: H
authors.lastname: Hu
authors.forename: Mingqian
authors.initials: M
authors.lastname: He
authors.forename: Ye
authors.initials: Y
authors.lastname: Fang
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D019390:Arrestins / Q000819:agonists* / Q000737:chemistry / Q000235:genetics; D001681:Biological Assay; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells; D006801:Humans; D008024:Ligands; D021381:Protein Transport / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000737:chemistry / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000819:agonists / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology; D000071557:beta-Arrestins
chemical_list: D000893:Anti-Inflammatory Agents; D019390:Arrestins; C111379:GPR35 protein, human; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D013876:Thiophenes; D000071557:beta-Arrestins