Novel compounds reducing IRS-1 serine phosphorylation for treatment of diabetes. Issue 2 (15th January 2016)

• Record Type: Journal Article
• Authors: Simon-Szabó, Laura; Kokas, Márton; Greff, Zoltán; Boros, Sándor; Bánhegyi, Péter; Zsákai, Lilián; Szántai-Kis, Csaba; Vantus, Tibor; Mandl, József; Bánhegyi, Gábor; Vályi-Nagy, István; Őrfi, László; Ullrich, Axel; Csala, Miklós; Kéri, György
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 2(2016)
• Page Start: 424
• Page End: 428
• Publication Date: 2016-01-15
• Subjects: TZVLWSNWONAKOX-UHFFFAOYSA-N -- QHPKKGUGRGRSGA-UHFFFAOYSA-N -- DTMZXHDQZQLTHA-UHFFFAOYSA-N -- LYNBNVBMAGDJRW-UHFFFAOYSA-N -- CPDLXBDVVJCDEQ-UHFFFAOYSA-N -- JYYLVUFNAHSSFE-UHFFFAOYSA-N -- HAVJVJFXQRMACG-UHFFFAOYSA-N -- FYTYWVADWQDNNG-UHFFFAOYSA-N -- GNRWBVNBKBFCAQ-UHFFFAOYSA-N -- JCZWGPOLOYAHME-UHFFFAOYSA-N -- XEDGIPZEQQIPKG-UHFFFAOYSA-N -- IJYAKYLQMNFAJH-UHFFFAOYSA-N -- XOEYHIASLQUJLZ-UHFFFAOYSA-N -- IRALUAJNHAVHJX-UHFFFAOYSA-N -- HQZLFWDMIGHLJC-UHFFFAOYSA-N -- QSLWILMHBLDNFG-UHFFFAOYSA-N -- MIRPOEPPAAEKAX-UHFFFAOYSA-N -- IWJMBVUMMQMCKL-UHFFFAOYSA-N -- WZTMLVYVSXWHRD-UHFFFAOYSA-N -- HPGHAQJNYIFAQZ-UHFFFAOYSA-N -- RBGTYQNUIHMBKM-UHFFFAOYSA-N -- LDTADWVWCRUXBO-UHFFFAOYSA-N -- HHBDQFLZIWRDQU-UHFFFAOYSA-N -- MNKDSVRFEDHLPU-UHFFFAOYSA-N -- ZRHGYSDRZJXCHG-UHFFFAOYSA-N -- FHZFRUHZBKDENV-UHFFFAOYSA-N -- IKCPKTRGNJUBMT-UHFFFAOYSA-N -- JMDLSDBBIDAGJC-UHFFFAOYSA-N -- BCTVGBJXUIOTRA-UHFFFAOYSA-N -- NVKGSBKKDOUQBL-UHFFFAOYSA-N -- CBPKAUGHLTVNHP-LBPRGKRZSA-N -- GDPNFRQTIUPZRF-UHFFFAOYSA-N -- XPLKLAPSYBBNLV-UHFFFAOYSA-N -- LMGJIECDPADVSW-NSHDSACASA-N -- GHPBSRHBIVNNEC-UHFFFAOYSA-N -- SQTGBOUGRATZKU-UHFFFAOYSA-N -- XSDBYWHPLWMHAX-UHFFFAOYSA-N -- DCUTZQNQYYZEMU-UHFFFAOYSA-N -- LIHDHWOPKVFJJI-UHFFFAOYSA-N -- MAPMGRSQBFNPGP-UHFFFAOYSA-N -- ZYHZCINGHGLKPH-UHFFFAOYSA-N -- SPHNPASRNFUBOV-UHFFFAOYSA-N -- RWBSDSJXLHIYCI-UHFFFAOYSA-N -- DBFDEQLIMUVSOV-UHFFFAOYSA-N -- CUOLILYHAIOACL-UHFFFAOYSA-N -- PWDHSXYQEDZMLP-UHFFFAOYSA-N; Type 2 diabetes -- Lipotoxicity -- c-Jun N-terminal kinase -- IRS-1 phosphorylation -- Pyrido[2, 3-d]pyrimidin; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.11.099
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Activation of various interacting stress kinases, particularly the c-Jun N-terminal kinases (JNK), and a concomitant phosphorylation of insulin receptor substrate 1 (IRS-1) at serine 307 play a central role both in insulin resistance and in β-cell dysfunction. IRS-1 phosphorylation is stimulated by elevated free fatty acid levels through different pathways in obesity. A series of novel pyrido[2, 3- d ]pyrimidin-7-one derivatives were synthesized as potential antidiabetic agents, preventing IRS-1 phosphorylation at serine 307 in a cellular model of lipotoxicity and type 2 diabetes.