Literature DB >> 22724451

Free fatty acid receptor 1 (FFA1/GPR40) agonists: mesylpropoxy appendage lowers lipophilicity and improves ADME properties.

Elisabeth Christiansen1, Maria E Due-Hansen, Christian Urban, Manuel Grundmann, Ralf Schröder, Brian D Hudson, Graeme Milligan, Michael A Cawthorne, Evi Kostenis, Matthias U Kassack, Trond Ulven.   

Abstract

FFA1 (GPR40) is a new target for treatment of type 2 diabetes. We recently identified the potent FFA1 agonist TUG-469 (5). Inspired by the structurally related TAK-875, we explored the effects of a mesylpropoxy appendage on 5. The appendage significantly lowers lipophilicity and improves metabolic stability while preserving potency, resulting in discovery of the potent FFA1 agonist 13.

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Year:  2012        PMID： 22724451     DOI： 10.1021/jm3002026

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  22 in total

1.  Physicochemical property-driven optimization of diarylaniline compounds as potent HIV-1 non-nucleoside reverse transcriptase inhibitors.

Authors:  Na Liu; Bingjie Qin; Lian-Qi Sun; Fei Yu; Lu Lu; Shibo Jiang; Kuo-Hsiung Lee; Lan Xie
Journal:  Bioorg Med Chem Lett       Date:  2014-07-11       Impact factor: 2.823

2.  An uncharged oxetanyl sulfoxide as a covalent modifier for improving aqueous solubility.

Authors:  Erin M Skoda; Joshua R Sacher; Mustafa Z Kazancioglu; Jaideep Saha; Peter Wipf
Journal:  ACS Med Chem Lett       Date:  2014-06-27       Impact factor: 4.345

Review 3.  Characterizing pharmacological ligands to study the long-chain fatty acid receptors GPR40/FFA1 and GPR120/FFA4.

Authors:  G Milligan; E Alvarez-Curto; K R Watterson; T Ulven; B D Hudson
Journal:  Br J Pharmacol       Date:  2015-02-27       Impact factor: 8.739

4.  Optimization of the antiviral potency and lipophilicity of halogenated 2,6-diarylpyridinamines as a novel class of HIV-1 NNRTIS.

Authors:  Zhi-Yuan Wu; Na Liu; Bingjie Qin; Li Huang; Fei Yu; Keduo Qian; Susan L Morris-Natschke; Shibo Jiang; Chin Ho Chen; Kuo-Hsiung Lee; Lan Xie
Journal:  ChemMedChem       Date:  2014-06-04       Impact factor: 3.466

Review 5.  Ligand binding at the protein-lipid interface: strategic considerations for drug design.

Authors:  Jian Payandeh; Matthew Volgraf
Journal:  Nat Rev Drug Discov       Date:  2021-07-13       Impact factor: 84.694

6.  Discovery and Optimization of Potent GPR40 Full Agonists Containing Tricyclic Spirocycles.

Authors:  Yingcai Wang; Jiwen Jim Liu; Paul J Dransfield; Liusheng Zhu; Zhongyu Wang; Xiaohui Du; Xianyun Jiao; Yongli Su; An-Rong Li; Sean P Brown; Annie Kasparian; Marc Vimolratana; Ming Yu; Vatee Pattaropong; Jonathan B Houze; Gayathri Swaminath; Thanhvien Tran; Khanh Nguyen; Qi Guo; Jane Zhang; Run Zhuang; Frank Li; Lynn Miao; Michael D Bartberger; Tiffany L Correll; David Chow; Simon Wong; Jian Luo; Daniel C-H Lin; Julio C Medina
Journal:  ACS Med Chem Lett       Date:  2013-05-07       Impact factor: 4.345

7.  In vitro and mouse in vivo characterization of the potent free fatty acid 1 receptor agonist TUG-469.

Authors:  C Urban; A Hamacher; H J Partke; M Roden; S Schinner; E Christiansen; M E Due-Hansen; T Ulven; H Gohlke; M U Kassack
Journal:  Naunyn Schmiedebergs Arch Pharmacol       Date:  2013-07-17       Impact factor: 3.000

Review 8.  Drugs or diet?--Developing novel therapeutic strategies targeting the free fatty acid family of GPCRs.

Authors:  H J Dranse; M E M Kelly; B D Hudson
Journal:  Br J Pharmacol       Date:  2013-10       Impact factor: 8.739

9.  An efficient multistep ligand-based virtual screening approach for GPR40 agonists.

Authors:  Sihui Yao; Tao Lu; Zifan Zhou; Haichun Liu; Haoliang Yuan; Ting Ran; Shuai Lu; Yanmin Zhang; Zhipeng Ke; Jinxing Xu; Xiao Xiong; Yadong Chen
Journal:  Mol Divers       Date:  2013-12-05       Impact factor: 2.943

10.  The pharmacology of TUG-891, a potent and selective agonist of the free fatty acid receptor 4 (FFA4/GPR120), demonstrates both potential opportunity and possible challenges to therapeutic agonism.

Authors:  Brian D Hudson; Bharat Shimpukade; Amanda E Mackenzie; Adrian J Butcher; John D Pediani; Elisabeth Christiansen; Helen Heathcote; Andrew B Tobin; Trond Ulven; Graeme Milligan
Journal:  Mol Pharmacol       Date:  2013-08-26       Impact factor: 4.436
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