Literature DB >> 24900845

Improving the Pharmacokinetics of GPR40/FFA1 Full Agonists.

Xiaohui Du1, Paul J Dransfield1, Daniel C-H Lin1, Simon Wong1, Yingcai Wang1, Zhongyu Wang1, Todd Kohn1, Ming Yu1, Sean P Brown1, Marc Vimolratana1, Liusheng Zhu1, An-Rong Li1, Yongli Su1, Xianyun Jiao1, Jiwen Jim Liu1, Gayathri Swaminath1, Thanhvien Tran1, Jian Luo1, Run Zhuang1, Jane Zhang1, Qi Guo1, Frank Li1, Richard Connors1, Julio C Medina1, Jonathan B Houze1.   

Abstract

We recently reported the discovery of a potent GPR40 full agonist AM-1638 (1). Herein, we describe our efforts in improving the drug-like properties of the full agonists through the systematic introduction of polar groups in the C-, D-, and A-rings. This led to the discovery of new GPR40 full agonists with significantly improved pharmacokinetic propeties. Compound 8 and 20 also showed potent in vivo efficacy in oral glucose tolerance tests in mice in addition to the improvement in properties.

Entities:  

Keywords:  FFA1; GPR40; full agonist; insulin secretagoue; type 2 diabetes

Year:  2014        PMID： 24900845      PMCID： PMC4027632          DOI： 10.1021/ml4005123

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


  14 in total

1.  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

2.  Design, synthesis, and biological activity of potent and orally available G protein-coupled receptor 40 agonists.

Authors:  Shinobu Sasaki; Shuji Kitamura; Nobuyuki Negoro; Masami Suzuki; Yoshiyuki Tsujihata; Nobuhiro Suzuki; Takashi Santou; Naoyuki Kanzaki; Masataka Harada; Yasuhiro Tanaka; Makoto Kobayashi; Norio Tada; Miyuki Funami; Toshimasa Tanaka; Yoshio Yamamoto; Kohji Fukatsu; Tsuneo Yasuma; Yu Momose
Journal:  J Med Chem       Date:  2011-02-14       Impact factor: 7.446

3.  Identification of a potent and selective free fatty acid receptor 1 (FFA1/GPR40) agonist with favorable physicochemical and in vitro ADME properties.

Authors:  Elisabeth Christiansen; Christian Urban; Manuel Grundmann; Maria E Due-Hansen; Ellen Hagesaether; Johannes Schmidt; Leonardo Pardo; Susanne Ullrich; Evi Kostenis; Matthias Kassack; Trond Ulven
Journal:  J Med Chem       Date:  2011-09-13       Impact factor: 7.446

4.  Risk of macrovascular and microvascular complications in Type 2 diabetes: results of longitudinal study design.

Authors:  Boguslawa Nazimek-Siewniak; DariuszK Moczulski; Wladyslaw Grzeszczak
Journal:  J Diabetes Complications       Date:  2002 Jul-Aug       Impact factor: 2.852

5.  A novel model of type 2 diabetes mellitus based on obesity induced by high-fat diet in BDF1 mice.

Authors:  Hiroshi Karasawa; Seiko Nagata-Goto; Kiyosumi Takaishi; Yoshihiro Kumagae
Journal:  Metabolism       Date:  2009-03       Impact factor: 8.694

Review 6.  Diabetes-associated macrovasculopathy: pathophysiology and pathogenesis.

Authors:  Sayeeda Rahman; Tahminur Rahman; Aziz Al-Shafi Ismail; Abdul Rahman A Rashid
Journal:  Diabetes Obes Metab       Date:  2007-11       Impact factor: 6.577

Review 7.  Pathophysiology and treatment of diabetic peripheral neuropathy: the case for diabetic neurovascular function as an essential component.

Authors:  Keri A Kles; Aaron I Vinik
Journal:  Curr Diabetes Rev       Date:  2006-05

8.  A potent class of GPR40 full agonists engages the enteroinsular axis to promote glucose control in rodents.

Authors:  Jian Luo; Gayathri Swaminath; Sean P Brown; Jane Zhang; Qi Guo; Michael Chen; Kathy Nguyen; Thanhvien Tran; Lynn Miao; Paul J Dransfield; Marc Vimolratana; Jonathan B Houze; Simon Wong; Maria Toteva; Bei Shan; Frank Li; Run Zhuang; Daniel C-H Lin
Journal:  PLoS One       Date:  2012-10-09       Impact factor: 3.240

9.  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

10.  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
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  4 in total

1.  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

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

Authors:  Helen Y Chen; Christopher W Plummer; Dong Xiao; Harry R Chobanian; Duane DeMong; Michael Miller; Maria E Trujillo; Melissa Kirkland; Daniel Kosinski; Joel Mane; Michele Pachanski; Boonlert Cheewatrakoolpong; Jerry Di Salvo; Brande Thomas-Fowlkes; Sarah Souza; Daniel A Tatosian; Qing Chen; Michael J Hafey; Robert Houle; Andrew F Nolting; Robert Orr; Juliann Ehrhart; Adam B Weinglass; Richard Tschirret-Guth; Andrew D Howard; Steven L Colletti
Journal:  ACS Med Chem Lett       Date:  2018-06-14       Impact factor: 4.345

3.  Discovery of AM-6226: A Potent and Orally Bioavailable GPR40 Full Agonist That Displays Efficacy in Nonhuman Primates.

Authors:  Sean P Brown; Paul Dransfield; Marc Vimolratana; Liusheng Zhu; Jian Luo; Jane Zhang; XianYun Jiao; Vatee Pattaropong; Simon Wong; Run Zhuang; Gayathri Swaminath; Jonathan B Houze; Daniel C-H Lin
Journal:  ACS Med Chem Lett       Date:  2018-06-06       Impact factor: 4.345

4.  Omega-3 fatty acids and other FFA4 agonists inhibit growth factor signaling in human prostate cancer cells.

Authors:  Ze Liu; Mandi M Hopkins; Zhihong Zhang; Chrystal B Quisenberry; Louise C Fix; Brianna M Galvan; Kathryn E Meier
Journal:  J Pharmacol Exp Ther       Date:  2014-12-09       Impact factor: 4.030
  4 in total

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