Discovery of 5-phenoxy-1,3-dimethyl-1H-pyrazole-4-carboxamides as potent agonists of TGR5 via sequential combinatorial libraries

Allyn T. Londregan, David W. Piotrowski, Kentaro Futatsugi, Joseph S. Warmus, Markus Boehm, Philip A. Carpino, Janice E. Chin, Ann M. Janssen, Nicole S. Roush, Joanne Buxton and Terri Hinchey

Bioorganic & Medicinal Chemistry Letters, 2013, 23, 1407
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Intramolecular Copper(I)‐Catalyzed Interrupted Click–Acylation Domino Reaction

Egor M. Larin and Mark Lautens

Angewandte Chemie, 2019, 131, 13572
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Discovery and optimisation of 1-hydroxyimino-3,3-diphenylpropanes, a new class of orally active GPBAR1 (TGR5) agonists

Henrietta Dehmlow, Rubén Alvarez Sánchez, Stephan Bachmann, Caterina Bissantz, Fritz Bliss, Karin Conde-Knape, Martin Graf, Rainer E. Martin, Ulrike Obst Sander, Susanne Raab, Hans G.F. Richter, Sabine Sewing, Urs Sprecher, Christoph Ullmer and Patrizio Mattei

Bioorganic & Medicinal Chemistry Letters, 2013, 23, 4627
DOI: 10.1016/j.bmcl.2013.06.017

G-Protein-Coupled Bile Acid Receptor 1 (GPBAR1, TGR5) Agonists Reduce the Production of Proinflammatory Cytokines and Stabilize the Alternative Macrophage Phenotype

Klemens Högenauer, Luca Arista, Niko Schmiedeberg, Gudrun Werner, Herbert Jaksche, Rochdi Bouhelal, Deborah G. Nguyen, B. Ganesh Bhat, Layla Raad, Celine Rauld and José M. Carballido

J. Med. Chem., 2014, 57, 10343
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Lithiation‐Functionalisation of Triazoles Bearing Electron‐Withdrawing N‐Substituents: Challenges and Solutions**

Frances E. Bugden, Guy J. Clarkson and Mark D. Greenhalgh

Eur J Org Chem, 2023, 26
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A GPBAR1 (TGR5) Small Molecule Agonist Shows Specific Inhibitory Effects on Myeloid Cell Activation In Vitro and Reduces Experimental Autoimmune Encephalitis (EAE) In Vivo

Nuruddeen D. Lewis, Lori A. Patnaude, Josephine Pelletier, Donald J. Souza, Susan M. Lukas, F. James King, Jonathan D. Hill, Dimitria E. Stefanopoulos, Kelli Ryan, Sudha Desai, Donna Skow, Stefan G. Kauschke, Andre Broermann, Daniel Kuzmich, Christian Harcken, Eugene R. Hickey, Louise K. Modis and Ralf Andreas Linker

PLoS ONE, 2014, 9, e100883
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G Protein–Coupled Bile Acid Receptor 1 Stimulation Mediates Arterial Vasodilation through a KCa1.1 (BKCa)–Dependent Mechanism

Ryan M. Fryer, Khing Jow Ng, Suzanne G. Nodop Mazurek, Lori Patnaude, Donna J. Skow, Akalushi Muthukumarana, Kyle E. Gilpin, Roger M. Dinallo, Daniel Kuzmich, John Lord, Sulagna Sanyal, Hui Yu, Christian Harcken, Matthew A. Cerny, Eugene R. Hickey and Louise K. Modis

The Journal of Pharmacology and Experimental Therapeutics, 2014, 348, 421
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Identification of Tetrahydropyrido[4,3-d]pyrimidine Amides as a New Class of Orally Bioavailable TGR5 Agonists

David W. Piotrowski, Kentaro Futatsugi, Joseph S. Warmus, Suvi T. M. Orr, Kevin D. Freeman-Cook, Allyn T. Londregan, Liuqing Wei, Sandra M. Jennings, Michael Herr, Steven B. Coffey, Wenhua Jiao, Gregory Storer, David Hepworth, Jian Wang, Sophie Y. Lavergne, Janice E. Chin, John R. Hadcock, Martin B. Brenner, Angela C. Wolford, Ann M. Janssen, Nicole S. Roush, Joanne Buxton, Terri Hinchey, Amit S. Kalgutkar, Raman Sharma and Declan A. Flynn

ACS Med. Chem. Lett., 2013, 4, 63
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Discovery of Trifluoromethyl(pyrimidin-2-yl)azetidine-2-carboxamides as Potent, Orally Bioavailable TGR5 (GPBAR1) Agonists: Structure–Activity Relationships, Lead Optimization, and Chronic In Vivo Efficacy

Dean P. Phillips, Wenqi Gao, Yang Yang, Guobao Zhang, Isabelle K. Lerario, Thomas L. Lau, Jiqing Jiang, Xia Wang, Deborah G. Nguyen, B. Ganesh Bhat, Carol Trotter, Heather Sullivan, Gustav Welzel, Jannine Landry, Yali Chen, Sean B. Joseph, Chun Li, W. Perry Gordon, Wendy Richmond, Kevin Johnson, Angela Bretz, Badry Bursulaya, Shifeng Pan, Peter McNamara and H. Martin Seidel

J. Med. Chem., 2014, 57, 3263
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Update on the development of TGR5 agonists for human diseases

Wangrui Jin, Mingyue Zheng, Yihua Chen and Hai Xiong

European Journal of Medicinal Chemistry, 2024, 271, 116462
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Discovery and Structure–Activity Relationship Study of 4-Phenoxythiazol-5-carboxamides as Highly Potent TGR5 Agonists

Zhixiang Chen, Mengmeng Ning, Qingan Zou, Hua Cao, Yangliang Ye, Ying Leng and Jianhua Shen

Chem. Pharm. Bull., 2016, 64, 326
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Clinical relevance of the bile acid receptor TGR5 in metabolism

F Samuel van Nierop, Matthijs J Scheltema, Hannah M Eggink, Thijs W Pols, David P Sonne, Filip K Knop and Maarten R Soeters

The Lancet Diabetes & Endocrinology, 2017, 5, 224
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Intestinally-targeted TGR5 agonists equipped with quaternary ammonium have an improved hypoglycemic effect and reduced gallbladder filling effect

Hua Cao, Zhi-Xiang Chen, Kai Wang, Meng-Meng Ning, Qing-An Zou, Ying Feng, Yang-Liang Ye, Ying Leng and Jian-Hua Shen

Sci Rep, 2016, 6
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Compound and compositions as TGR5 agonists: WO2012082947

Saurin Raval

Expert Opinion on Therapeutic Patents, 2013, 23, 531
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Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets

Joshua S. Fleishman and Sunil Kumar

Sig Transduct Target Ther, 2024, 9
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Discovery of Orally Efficacious Tetrahydrobenzimidazoles as TGR5 Agonists for Type 2 Diabetes

Xuqing Zhang, Mark Wall, Zhihua Sui, Jack Kauffman, Cuifen Hou, Cailin Chen, Fuyong Du, Thomas Kirchner, Yin Liang, Dana L. Johnson, William V. Murray and Keith Demarest

ACS Med. Chem. Lett., 2017, 8, 560
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Design, Synthesis, and Structure–Activity Relationships of 3,4,5‐Trisubstituted 4,5‐Dihydro‐1,2,4‐oxadiazoles as TGR5 Agonists

Junjie Zhu, Yangliang Ye, Mengmeng Ning, Attila Mándi, Ying Feng, Qingan Zou, Tibor Kurtán, Ying Leng and Jianhua Shen

ChemMedChem, 2013, 8, 1210
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Identification of new non-steroidal TGR5 agonists using virtual screening with combined pharmacophore models

Chen Zhou, Fangxia Zou, Yungen Xu, Luyong Zhang and Xiaoming Zha

Med Chem Res, 2015, 24, 2561
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Intramolecular Copper(I)‐Catalyzed Interrupted Click–Acylation Domino Reaction

Egor M. Larin and Mark Lautens

Angew Chem Int Ed, 2019, 58, 13438
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Late-Stage Functionalization Strategies of 1,2,3-Triazoles: A Post-Click Approach in Organic Synthesis

Mangal S. Yadav, Vinay K. Pandey, Manoj K. Jaiswal, Sumit K. Singh, Anindra Sharma, Mayank Singh and Vinod K. Tiwari

J. Org. Chem., 2025, 90, 5731
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Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist

Sameer Agarwal, Amit Patil, Umesh Aware, Prashant Deshmukh, Brijesh Darji, Santosh Sasane, Kalapatapu V. V. M. Sairam, Priyanka Priyadarsiny, Poonam Giri, Harilal Patel, Suresh Giri, Mukul Jain and Ranjit C. Desai

ACS Med. Chem. Lett., 2016, 7, 51
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Recent Progress on Bile Acid Receptor Modulators for Treatment of Metabolic Diseases

Yanping Xu

J. Med. Chem., 2016, 59, 6553
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Novel 2-mercapto imidazole and triazole derivatives as potent TGR5 receptor agonists

Sameer Agarwal, Santosh Sasane, Jeevan Kumar, Brijesh Darji, Hitesh Bhayani, Shubhangi Soman, Neelima Kulkarni and Mukul Jain

Medicine in Drug Discovery, 2019, 1, 100002
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Topical Intestinal Aminoimidazole Agonists of G-Protein-Coupled Bile Acid Receptor 1 Promote Glucagon Like Peptide-1 Secretion and Improve Glucose Tolerance

Manuel Lasalle, Vanessa Hoguet, Nathalie Hennuyer, Florence Leroux, Catherine Piveteau, Loïc Belloy, Sophie Lestavel, Emmanuelle Vallez, Emilie Dorchies, Isabelle Duplan, Emmanuel Sevin, Maxime Culot, Fabien Gosselet, Rajaa Boulahjar, Adrien Herledan, Bart Staels, Benoit Deprez, Anne Tailleux and Julie Charton

J. Med. Chem., 2017, 60, 4185
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Evaluation of anti-diabetic effect and gall bladder function with 2-thio-5-thiomethyl substituted imidazoles as TGR5 receptor agonists

Xuqing Zhang, Zhihua Sui, Jack Kauffman, Cuifen Hou, Cailin Chen, Fuyong Du, Thomas Kirchner, Yin Liang, Dana Johnson, William V. Murray and Keith Demarest

Bioorganic & Medicinal Chemistry Letters, 2017, 27, 1760
DOI: 10.1016/j.bmcl.2017.02.069

Deuterium isotope effects in drug pharmacokinetics II: Substrate-dependence of the reaction mechanism influences outcome for cytochrome P450 cleared drugs

Hao Sun, David W. Piotrowski, Suvi T. M. Orr, Joseph S. Warmus, Angela C. Wolford, Steven B. Coffey, Kentaro Futatsugi, Yinsheng Zhang, Alfin D. N. Vaz and Markos Leggas

PLoS ONE, 2018, 13, e0206279
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Discovery, Structure–Activity Relationships, and In Vivo Activity of Dihydropyridone Agonists of the Bile Acid Receptor TGR5

Sylvain Picon, Rajaa Boulahjar, Vanessa Hoguet, Morgane Baron, Isabelle Duplan, Emmanuelle Vallez, Nathalie Hennuyer, Julie Dumont, Véronique Touche, Emilie Dorchies, Manuel Lasalle, Amandine Descat, Catherine Piveteau, Alexandre Biela, Ludovic Chaput, Bruno O. Villoutreix, Emmanuelle Lipka, Emmanuel Sevin, Maxime Culot, Fabien Gosselet, Sophie Lestavel, Pascal Roussel, Rebecca Deprez-Poulain, Florence Leroux, Bart Staels, Benoit Deprez, Anne Tailleux and Julie Charton

J. Med. Chem., 2023, 66, 11732
DOI: 10.1021/acs.jmedchem.2c01881