Literature DB >> 30034601

Structure-Activity Relationship of Novel and Selective Biaryl-Chroman GPR40 AgoPAMs.

Helen Y Chen1, Christopher W Plummer1, Dong Xiao1, Harry R Chobanian1, Duane DeMong1, Michael Miller1, Maria E Trujillo1, Melissa Kirkland1, Daniel Kosinski1, Joel Mane1, Michele Pachanski1, Boonlert Cheewatrakoolpong1, Jerry Di Salvo1, Brande Thomas-Fowlkes1, Sarah Souza1, Daniel A Tatosian1, Qing Chen1, Michael J Hafey1, Robert Houle1, Andrew F Nolting1, Robert Orr1, Juliann Ehrhart1, Adam B Weinglass1, Richard Tschirret-Guth1, Andrew D Howard1, Steven L Colletti1.   

Abstract

A series of biaryl chromans exhibiting potent and selective agonism for the GPR40 receptor with positive allosteric modulation of endogenous ligands (AgoPAM) were discovered as potential therapeutics for the treatment of type II diabetes. Optimization of physicochemical properties through modification of the pendant aryl rings resulted in the identification of compound AP5, which possesses an improved metabolic profile while demonstrating sustained glucose lowering.

Entities:  

Year:  2018        PMID： 30034601      PMCID： PMC6047031          DOI： 10.1021/acsmedchemlett.8b00149

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  17 in total

1.  Interspecies prediction of human drug clearance based on scaling data from one or two animal species.

Authors:  Huadong Tang; Azher Hussain; Mauricio Leal; Michael Mayersohn; Eric Fluhler
Journal:  Drug Metab Dispos       Date:  2007-07-23       Impact factor: 3.922

Review 2.  Emerging paradigms in GPCR allostery: implications for drug discovery.

Authors:  Denise Wootten; Arthur Christopoulos; Patrick M Sexton
Journal:  Nat Rev Drug Discov       Date:  2013-08       Impact factor: 84.694

3.  Design and Synthesis of Novel, Selective GPR40 AgoPAMs.

Authors:  Christopher W Plummer; Matthew J Clements; Helen Chen; Murali Rajagopalan; Hubert Josien; William K Hagmann; Michael Miller; Maria E Trujillo; Melissa Kirkland; Daniel Kosinski; Joel Mane; Michele Pachanski; Boonlert Cheewatrakoolpong; Andrew F Nolting; Robert Orr; Melodie Christensen; Louis-Charles Campeau; Michael J Wright; Randal Bugianesi; Sarah Souza; Xiaoping Zhang; Jerry Di Salvo; Adam B Weinglass; Richard Tschirret-Guth; Ravi Nargund; Andrew D Howard; Steven L Colletti
Journal:  ACS Med Chem Lett       Date:  2017-01-23       Impact factor: 4.345

4.  Improving the Pharmacokinetics of GPR40/FFA1 Full Agonists.

Authors:  Xiaohui Du; Paul J Dransfield; Daniel C-H Lin; Simon Wong; Yingcai Wang; Zhongyu Wang; Todd Kohn; Ming Yu; Sean P Brown; Marc Vimolratana; Liusheng Zhu; An-Rong Li; Yongli Su; Xianyun Jiao; Jiwen Jim Liu; Gayathri Swaminath; Thanhvien Tran; Jian Luo; Run Zhuang; Jane Zhang; Qi Guo; Frank Li; Richard Connors; Julio C Medina; Jonathan B Houze
Journal:  ACS Med Chem Lett       Date:  2014-02-03       Impact factor: 4.345

5.  In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans.

Authors:  Sarah Dawson; Simone Stahl; Nikki Paul; Jane Barber; J Gerald Kenna
Journal:  Drug Metab Dispos       Date:  2011-09-30       Impact factor: 3.922

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.  AMG 837: a potent, orally bioavailable GPR40 agonist.

Authors:  Jonathan B Houze; Liusheng Zhu; Ying Sun; Michelle Akerman; Wei Qiu; Alex J Zhang; Rajiv Sharma; Michael Schmitt; Yingcai Wang; Jiwen Liu; Jinqian Liu; Julio C Medina; Jeff D Reagan; Jian Luo; George Tonn; Jane Zhang; Jenny Ying-Lin Lu; Michael Chen; Edwin Lopez; Kathy Nguyen; Li Yang; Liang Tang; Hui Tian; Steven J Shuttleworth; Daniel C-H Lin
Journal:  Bioorg Med Chem Lett       Date:  2011-11-06       Impact factor: 2.940

8.  Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus.

Authors:  Ralph A Defronzo
Journal:  Diabetes       Date:  2009-04       Impact factor: 9.461

9.  Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion.

Authors:  Sara Edfalk; Pär Steneberg; Helena Edlund
Journal:  Diabetes       Date:  2008-06-02       Impact factor: 9.461

10.  GPR40 partial agonists and AgoPAMs: Differentiating effects on glucose and hormonal secretions in the rodent.

Authors:  Michele J Pachanski; Melissa E Kirkland; Daniel T Kosinski; Joel Mane; Boonlert Cheewatrakoolpong; Jiyan Xue; Daphne Szeto; Gail Forrest; Corin Miller; Michelle Bunzel; Christopher W Plummer; Harry R Chobanian; Michael W Miller; Sarah Souza; Brande S Thomas-Fowlkes; Aimie M Ogawa; Adam B Weinglass; Jerry Di Salvo; Xiaoyan Li; Yue Feng; Daniel A Tatosian; Andrew D Howard; Steven L Colletti; Maria E Trujillo
Journal:  PLoS One       Date:  2017-10-20       Impact factor: 3.240
View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.