title: Synthesis and biological evaluation of thienopyrimidine derivatives as GPR119 agonists.
abstract: A series of thienopyrimidine derivatives was synthesized and evaluated for their GPR119 agonistic ability. Several thienopyrimidine derivatives containing R(1) and R(2) substituents displayed potent GPR119 agonistic activity. Among them, compound 5d, which is a prototype, showed good in vitro activity with an EC50 value of 3 nM and human and rat liver microsomal stability. Compound 5d exhibited no CYP inhibition and induction, Herg binding, or mutagenic potential. Compound 5d showed increase insulin secretion in beta TC-6 cell and lowered the glucose excursion in mice in an oral glucose-tolerance test.
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Republic of Korea.
authors.forename: Moon-Kook
authors.initials: MK
authors.lastname: Jeon
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Republic of Korea.
authors.forename: Kyu Myung
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Republic of Korea.
authors.forename: Il Hyang
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Republic of Korea; Department of Medicinal and Pharmaceutical Chemistry, University of Science and Technology, 305-333, Republic of Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jang
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Republic of Korea.
authors.forename: Seung Kyu
authors.initials: SK
authors.lastname: Kang
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Republic of Korea.
authors.forename: Jun Mi
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Republic of Korea.
authors.forename: Kwan-Young
authors.initials: KY
authors.lastname: Jung
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Republic of Korea.
authors.forename: Jaladi Ashok
authors.initials: JA
authors.lastname: Kumar
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Republic of Korea.
authors.forename: Sang Dal
authors.initials: SD
authors.lastname: Rhee
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Republic of Korea.
authors.forename: Won Hoon
authors.initials: WH
authors.lastname: Jung
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Republic of Korea.
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Song
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Republic of Korea.
authors.forename: Myung Ae
authors.initials: MA
authors.lastname: Bae
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Republic of Korea.
authors.forename: Kwang Rok
authors.initials: KR
authors.lastname: Kim
authors.affiliation: Drug Discovery Division, Korea Research Institute of Chemical Technology, Republic of Korea; Department of Medicinal and Pharmaceutical Chemistry, University of Science and Technology, 305-333, Republic of Korea. Electronic address: jhahn@krict.re.kr.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Ahn
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D051379:Mice; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D001786:Blood Glucose; C519854:GPR119 protein, human; D007328:Insulin; D011743:Pyrimidines; D043562:Receptors, G-Protein-Coupled; C476003:thienopyrimidine
keywords: Diabetes; GPR119; Thienopyrimidine; Treatment