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6α-Ethyl-Chenodeoxycholic Acid (6-ECDCA), a Potent and Selective FXR Agonist Endowed with Anticholestatic Activity

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Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Via del Liceo, 06123 Perugia, Italy, Dipartimento di Medicina Clinica e Sperimentale, Clinica di Gastroenterologia ed Epatologia, Università di Perugia, 06123 Perugia, Italy, and Discovery Research, GlaxoSmithKline, Research Triangle Park, North Carolina 27709
Cite this: J. Med. Chem. 2002, 45, 17, 3569–3572
Publication Date (Web):July 20, 2002
https://doi.org/10.1021/jm025529g
Copyright © 2002 American Chemical Society

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    Abstract

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    A series of 6α-alkyl-substituted analogues of chenodeoxycholic acid (CDCA) were synthesized and evaluated as potential farnesoid X receptor (FXR) ligands. Among them, 6α-ethyl-chenodeoxycholic acid (6-ECDCA) was shown to be a very potent and selective FXR agonist (EC50 = 99 nM) and to be endowed with anticholeretic activity in an in vivo rat model of cholestasis.

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     To whom correspondence should be addressed. Tel:  +39 075 585 5120. Fax:  +39 075 585 5124. E-mail:  [email protected].

     Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia.

    §

     Dipartimento di Medicina Clinica e Sperimentale, Università di Perugia.

     GlaxoSmithKline.

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    29. Valentina Sepe, Giuseppe Bifulco, Barbara Renga, Claudio D’Amore, Stefano Fiorucci, and Angela Zampella . Discovery of Sulfated Sterols from Marine Invertebrates as a New Class of Marine Natural Antagonists of Farnesoid-X-Receptor. Journal of Medicinal Chemistry 2011, 54 (5) , 1314-1320. https://doi.org/10.1021/jm101336m
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    36. Antimo Gioiello, Emiliano Rosatelli, Bruno Cerra. Patented Farnesoid X receptor modulators: a review (2019 – present). Expert Opinion on Therapeutic Patents 2024, 79 , 1-18. https://doi.org/10.1080/13543776.2024.2314296
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    46. Emiliano Rosatelli, Andrea Carotti, Bruno Cerra, Francesca De Franco, Daniela Passeri, Roberto Pellicciari, Antimo Gioiello. Chemical exploration of TGR5 functional hot-spots: Synthesis and structure-activity relationships of C7- and C23-Substituted cholic acid derivatives. European Journal of Medicinal Chemistry 2023, 261 , 115851. https://doi.org/10.1016/j.ejmech.2023.115851
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    48. Luciano Adorini, Michael Trauner. FXR agonists in NASH treatment. Journal of Hepatology 2023, 79 (5) , 1317-1331. https://doi.org/10.1016/j.jhep.2023.07.034
    49. Arun J. Sanyal, Vlad Ratziu, Rohit Loomba, Quentin M. Anstee, Kris V. Kowdley, Mary E. Rinella, Muhammad Y. Sheikh, James F. Trotter, Whitfield Knapple, Eric J. Lawitz, Manal F. Abdelmalek, Philip N. Newsome, Jérôme Boursier, Philippe Mathurin, Jean-François Dufour, M. Michelle Berrey, Steven J. Shiff, Sangeeta Sawhney, Thomas Capozza, Rina Leyva, Stephen A. Harrison, Zobair M. Younossi. Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre-cirrhotic fibrosis due to non-alcoholic steatohepatitis. Journal of Hepatology 2023, 79 (5) , 1110-1120. https://doi.org/10.1016/j.jhep.2023.07.014
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    53. Annarosa Floreani, Daniela Gabbia, Sara De Martin. Primary biliary cholangitis: primary autoimmune disease or primary secretory defect. Expert Review of Gastroenterology & Hepatology 2023, 17 (9) , 863-870. https://doi.org/10.1080/17474124.2023.2242771
    54. Yuhua Gao, Jun Lin, Chuan Ye, Siqi Guo, Changtao Jiang. Microbial transformations of bile acids and their receptors in the regulation of metabolic dysfunction-associated steatotic liver disease. Liver Research 2023, 7 (3) , 165-176. https://doi.org/10.1016/j.livres.2023.09.002
    55. Dan Shan, Siyu Dai, Qian Chen, Yupei Xie, Yayi Hu. Hepatoprotective agents in the management of intrahepatic cholestasis of pregnancy: current knowledge and prospects. Frontiers in Pharmacology 2023, 14 https://doi.org/10.3389/fphar.2023.1218432
    56. Kenneth C. P. Cheung, Jiao Ma, Rodrigo Azevedo Loiola, Xingxuan Chen, Wei Jia. Bile acid‐activated receptors in innate and adaptive immunity: targeted drugs and biological agents. European Journal of Immunology 2023, 53 (8) https://doi.org/10.1002/eji.202250299
    57. Eileen L. Yoon, Won Kim. Current and future treatment for alcoholic‐related liver diseases. Journal of Gastroenterology and Hepatology 2023, 38 (8) , 1218-1226. https://doi.org/10.1111/jgh.16257
    58. Reeju Amatya, Donghee Lee, Kyoung Ah Min, Meong Cheol Shin. Pharmaceutical Strategies to Improve Druggability of Potential Drug Candidates in Nonalcoholic Fatty Liver Disease Therapy. Pharmaceutics 2023, 15 (7) , 1963. https://doi.org/10.3390/pharmaceutics15071963
    59. Danmei Yu, Zhou Lu, Ruyu Wang, Yusen Xiang, Hongtao Li, Jiani Lu, Lijun Zhang, Hongzhuan Chen, Weihua Li, Xin Luan, Lili Chen. FXR agonists for colorectal and liver cancers, as a stand-alone or in combination therapy. Biochemical Pharmacology 2023, 212 , 115570. https://doi.org/10.1016/j.bcp.2023.115570
    60. Anna C. Croce, Andrea Ferrigno, Giuseppina Palladini, Barbara Mannucci, Mariapia Vairetti, Laura G. Di Pasqua. Fatty Acids and Bilirubin as Intrinsic Autofluorescence Serum Biomarkers of Drug Action in a Rat Model of Liver Ischemia and Reperfusion. Molecules 2023, 28 (9) , 3818. https://doi.org/10.3390/molecules28093818
    61. Hao Ma, Yunyang Bao, Shuaishuai Niu, Shaorong Wang, Yiming Li, Hongwei He, Na Zhang, Weishuo Fang. Structure Optimization of 12β-O-γ-Glutamyl Oleanolic Acid Derivatives Resulting in Potent FXR Antagonist/Modulator for NASH Therapy. Pharmaceuticals 2023, 16 (5) , 758. https://doi.org/10.3390/ph16050758
    62. Song Yang, Hongyun Li, Yuanyuan Gu, Qiang Wang, Li Dong, Chao Xu, Yuxin Fan, Ming Liu, Qingbo Guan, Lixing Ma. The association between total bile acid and bone mineral density among patients with type 2 diabetes. Frontiers in Endocrinology 2023, 14 https://doi.org/10.3389/fendo.2023.1153205
    63. Caezaan Keshvani, Jonathan Kopel, Hemant Goyal. Obeticholic Acid—A Pharmacological and Clinical Review. Future Pharmacology 2023, 3 (1) , 238-251. https://doi.org/10.3390/futurepharmacol3010017
    64. Andreas Luxenburger, Lawrence D. Harris, Elizabeth M. Ure, Wanting Jiao, Anthony D. Woolhouse, Scott A. Cameron, Alex Weymouth-Wilson, Richard H. Furneaux, Janet L. Pitman, Simon F.R. Hinkley. The discovery of 12β-methyl-17-epi-18-nor-bile acids as potent and selective TGR5 agonists. European Journal of Medicinal Chemistry 2023, 250 , 115143. https://doi.org/10.1016/j.ejmech.2023.115143
    65. M. H. Zalzala, W. S. Al-khfajy, R. A. Khaleel. Cytotoxic Effect of 6-Ethyl-Chenodeoxycholic Acid and Cabazitaxel on PC-3 Cells. Drug development & registration 2023, 12 (1) , 52-58. https://doi.org/10.33380/2305-2066-2023-12-1-52-58
    66. Dong-Hyun Kim, Jung Sun Park, Hoon-In Choi, Chang Seong Kim, Eun Hui Bae, Seong Kwon Ma, Soo Wan Kim. The role of the farnesoid X receptor in kidney health and disease: a potential therapeutic target in kidney diseases. Experimental & Molecular Medicine 2023, 55 (2) , 304-312. https://doi.org/10.1038/s12276-023-00932-2
    67. Eun Jeoung Lee, Yun Kim, Ji Eun Kim, Eileen Laurel Yoon, Sung Ryol Lee, Dae Won Jun. ALS-L1023 from Melissa officinalis Alleviates Liver Fibrosis in a Non-Alcoholic Fatty Liver Disease Model. Life 2023, 13 (1) , 100. https://doi.org/10.3390/life13010100
    68. Cristina Zivko, Finja Witt, Andreas Koeberle, Gregor Fuhrmann, Paola Luciani. Formulating elafibranor and obeticholic acid with phospholipids decreases drug-induced association of SPARC to extracellular vesicles from LX-2 human hepatic stellate cells. European Journal of Pharmaceutics and Biopharmaceutics 2023, 182 , 32-40. https://doi.org/10.1016/j.ejpb.2022.11.025
    69. Huanhuan Cao, Yujie Zhu, Gaofei Hu, Qi Zhang, Lemin Zheng. Gut microbiome and metabolites, the future direction of diagnosis and treatment of atherosclerosis?. Pharmacological Research 2023, 187 , 106586. https://doi.org/10.1016/j.phrs.2022.106586
    70. Aalam Sohal, Kris V Kowdley. Primary Biliary Cholangitis: Promising Emerging Innovative Therapies and Their Impact on GLOBE Scores. Hepatic Medicine: Evidence and Research 2023, Volume 15 , 63-77. https://doi.org/10.2147/HMER.S361077
    71. Yilin Li, Rong Lei, Honglin Lei, Qin Xiong, Fengjiao Xie, Chengjiao Yao, Peimin Feng. Side effect profile of pharmacologic therapies for liver fibrosis in nonalcoholic fatty liver disease: a systematic review and network meta-analysis. European Journal of Gastroenterology & Hepatology 2023, 35 (1) , 1-14. https://doi.org/10.1097/MEG.0000000000002471
    72. Chuan Ding, Zeping Wang, Xinyue Dou, Qiao Yang, Yan Ning, Shi Kao, Xianan Sang, Min Hao, Kuilong Wang, Mengyun Peng, Shuosheng Zhang, Xin Han, Gang Cao. Farnesoid X receptor: From Structure to Function and Its Pharmacology in Liver Fibrosis. Aging and disease 2023, , 0. https://doi.org/10.14336/AD.2023.0830
    73. Linyu Pan, Ze Yu, Xiaolin Liang, Jiyou Yao, Yanfang Fu, Xu He, Xiaoling Ren, Jiajia Chen, Xuejuan Li, Minqiang Lu, Tian Lan. Sodium cholate ameliorates nonalcoholic steatohepatitis by activation of FXR signaling. Hepatology Communications 2023, 7 (2) , e0039-e0039. https://doi.org/10.1097/HC9.0000000000000039
    74. Cheng Han Ng, Ansel Shao Pin Tang, Jieling Xiao, Zhen Yu Wong, Jie Ning Yong, Clarissa E. Fu, Rebecca W. Zeng, Caitlyn Tan, Gabriel Hong Zhe Wong, Margaret Teng, Douglas Chee, Darren Jun Hao Tan, Kai En Chan, Daniel Q. Huang, Nicholas W.S. Chew, Benjamin Nah, Mohammad S. Siddqui, Arun J. Sanyal, Mazen Noureddin, Mark Muthiah. Safety and tolerability of obeticholic acid in chronic liver disease: a pooled analysis of 1878 individuals. Hepatology Communications 2023, 7 (3) , e0005-e0005. https://doi.org/10.1097/HC9.0000000000000005
    75. Lucia Sessa, Simona Concilio, Jesús Fominaya, Daniela Eletto, Stefano Piotto, Xavier Busquets. A new serotonin 2A receptor antagonist with potential benefits in non-alcoholic fatty liver disease. Life Sciences 2022, 37 , 121315. https://doi.org/10.1016/j.lfs.2022.121315
    76. Jinying Gu, Qiuyu Wu, Qiuyue Zhang, Qidong You, Lei Wang. A decade of approved first-in-class small molecule orphan drugs: Achievements, challenges and perspectives. European Journal of Medicinal Chemistry 2022, 243 , 114742. https://doi.org/10.1016/j.ejmech.2022.114742
    77. Cosimo Giannini, Concetta Mastromauro, Serena Scapaticci, Cristina Gentile, Francesco Chiarelli. Role of bile acids in overweight and obese children and adolescents. Frontiers in Endocrinology 2022, 13 https://doi.org/10.3389/fendo.2022.1011994
    78. Silvia Marchianò, Michele Biagioli, Rosalinda Roselli, Angela Zampella, Cristina Di Giorgio, Martina Bordoni, Rachele Bellini, Ginevra Urbani, Elva Morretta, Maria Chiara Monti, Eleonora Distrutti, Stefano Fiorucci. Beneficial effects of UDCA and norUDCA in a rodent model of steatosis are linked to modulation of GPBAR1/FXR signaling. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 2022, 1867 (11) , 159218. https://doi.org/10.1016/j.bbalip.2022.159218
    79. Christoph Schramm, Heiner Wedemeyer, Andrew Mason, Gideon M. Hirschfield, Cynthia Levy, Kris V. Kowdley, Piotr Milkiewicz, Ewa Janczewska, Elena Sergeevna Malova, Johanne Sanni, Phillip Koo, Jin Chen, Subhajit Choudhury, Lloyd B. Klickstein, Michael K. Badman, David Jones. Farnesoid X receptor agonist tropifexor attenuates cholestasis in a randomised trial in patients with primary biliary cholangitis. JHEP Reports 2022, 4 (11) , 100544. https://doi.org/10.1016/j.jhepr.2022.100544
    80. Zihang Yuan, Jie Wang, Haoran Zhang, Yingying Miao, Qianhui Tang, Ziqiao Yuan, Cheng Nong, Zhicheng Duan, Luyong Zhang, Zhenzhou Jiang, Qinwei Yu. Triptolide increases resistance to bile duct ligation-induced liver injury and fibrosis in mice by inhibiting RELB. Frontiers in Nutrition 2022, 9 https://doi.org/10.3389/fnut.2022.1032722
    81. Mengjiao Zhou, Danfeng Wang, Xiang Li, Ying Cao, Chengxue Yi, Dickson Kofi Wiredu Ocansey, Yuling Zhou, Fei Mao. Farnesoid-X receptor as a therapeutic target for inflammatory bowel disease and colorectal cancer. Frontiers in Pharmacology 2022, 13 https://doi.org/10.3389/fphar.2022.1016836
    82. Frederik Nevens, Michael Trauner, Michael P. Manns. Primary biliary cholangitis as a roadmap for the development of novel treatments for cholestatic liver diseases†. Journal of Hepatology 2022, 34–35 https://doi.org/10.1016/j.jhep.2022.10.007
    83. Thanatharayil Sathian Aishwarya, Nadella Mounika, Gayatri Vishwakarma, Ramu Adela. Effect of obeticholic acid in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) patients: a systematic review and meta-analysis. RPS Pharmacy and Pharmacology Reports 2022, 1 (1) https://doi.org/10.1093/rpsppr/rqac001
    84. Yangshuo Li, Kaili Wang, Jie Ding, Shuai Sun, Zhexin Ni, Chaoqin Yu. Influence of the gut microbiota on endometriosis: Potential role of chenodeoxycholic acid and its derivatives. Frontiers in Pharmacology 2022, 13 https://doi.org/10.3389/fphar.2022.954684
    85. Mamun Al Mahtab, Sheikh Mohammad Fazle Akbar, Partho Pratik Roy, Mohammad Abdur Rahim, SM Sabrina Yesmin, Sunan Bin Islam. Treatment of Nonalcoholic Steatohepatitis by Obeticholic Acid: Current Status. Euroasian Journal of Hepato-Gastroenterology 2022, 12 (S1) , S46-S50. https://doi.org/10.5005/jp-journals-10018-1360
    86. Rumei Li, Milaine V. Hovingh, Martijn Koehorst, Pim de Blaauw, Henkjan J. Verkade, Jan Freark de Boer, Folkert Kuipers. Short-term obeticholic acid treatment does not impact cholangiopathy in Cyp2c70-deficient mice with a human-like bile acid composition. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 2022, 1867 (8) , 159163. https://doi.org/10.1016/j.bbalip.2022.159163
    87. Shuni Duan, Xiaojiaoyang Li, Guifang Fan, Runping Liu. Targeting bile acid signaling for the treatment of liver diseases: From bench to bed. Biomedicine & Pharmacotherapy 2022, 152 , 113154. https://doi.org/10.1016/j.biopha.2022.113154
    88. Katrin Panzitt, Gernot Zollner, Hanns-Ulrich Marschall, Martin Wagner. Recent advances on FXR-targeting therapeutics. Molecular and Cellular Endocrinology 2022, 552 , 111678. https://doi.org/10.1016/j.mce.2022.111678
    89. Rasha A. Tawfiq, Noha N. Nassar, Olfat A. Hammam, Rasha M. Allam, Mohamed M. Elmazar, Dalaal M. Abdallah, Yasmeen M. Attia. Obeticholic acid orchestrates the crosstalk between ileal autophagy and tight junctions in non-alcoholic steatohepatitis: Role of TLR4/TGF-β1 axis. Chemico-Biological Interactions 2022, 361 , 109953. https://doi.org/10.1016/j.cbi.2022.109953
    90. Stefano Fiorucci, Angela Zampella, Patrizia Ricci, Eleonora Distrutti, Michele Biagioli. Immunomodulatory functions of FXR. Molecular and Cellular Endocrinology 2022, 551 , 111650. https://doi.org/10.1016/j.mce.2022.111650
    91. Yiming Ni, Mengna Lu, Yuan Xu, Qixue Wang, Xinyi Gu, Ying Li, Tongxi Zhuang, Chenyi Xia, Ting Zhang, Xiao-jun Gou, Mingmei Zhou. The Role of Gut Microbiota-Bile Acids Axis in the Progression of Non-alcoholic Fatty Liver Disease. Frontiers in Microbiology 2022, 13 https://doi.org/10.3389/fmicb.2022.908011
    92. Ji-Won Park, Jung-Hee Kim, Sung-Eun Kim, Jang Han Jung, Myoung-Kuk Jang, Sang-Hoon Park, Myung-Seok Lee, Hyoung-Su Kim, Ki Tae Suk, Dong Joon Kim. Primary Biliary Cholangitis and Primary Sclerosing Cholangitis: Current Knowledge of Pathogenesis and Therapeutics. Biomedicines 2022, 10 (6) , 1288. https://doi.org/10.3390/biomedicines10061288
    93. P. Barton Duell, Francine K. Welty, Michael Miller, Alan Chait, Gmerice Hammond, Zahid Ahmad, David E. Cohen, Jay D. Horton, Gregg S. Pressman, Peter P. Toth, . Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association. Arteriosclerosis, Thrombosis, and Vascular Biology 2022, 42 (6) https://doi.org/10.1161/ATV.0000000000000153
    94. Weilong Hong, Xuyun Peng, Xue Zhou, Panlong Li, Zhiqiang Ye, Weicheng Liang. FXR/ASS1 axis attenuates the TAA-induced liver injury through arginine metabolism. Biochemical and Biophysical Research Communications 2022, 611 , 31-37. https://doi.org/10.1016/j.bbrc.2022.04.073
    95. Chuangzhen Lin, Bingqing Yu, Xuelian Liu, Lixin Chen, Zhaohui Zhang, Weixiang Ye, Hui Zhong, Wenke Bai, Yuping Yang, Biao Nie. Obeticholic acid inhibits hepatic fatty acid uptake independent of FXR in mouse. Biomedicine & Pharmacotherapy 2022, 150 , 112984. https://doi.org/10.1016/j.biopha.2022.112984
    96. Chuangzhen Lin, Bingqing Yu, Lixin Chen, Zhaohui Zhang, Weixiang Ye, Hui Zhong, Wenke Bai, Yuping Yang, Biao Nie. Obeticholic Acid Induces Hepatoxicity Via FXR in the NAFLD Mice. Frontiers in Pharmacology 2022, 13 https://doi.org/10.3389/fphar.2022.880508
    97. Elizabeth M. Ure, Lawrence D. Harris, Scott A. Cameron, Alex Weymouth-Wilson, Richard H. Furneaux, Janet L. Pitman, Simon. F. Hinkley, Andreas Luxenburger. Synthesis of 12β-methyl-18- nor -avicholic acid analogues as potential TGR5 agonists. Organic & Biomolecular Chemistry 2022, 20 (17) , 3511-3527. https://doi.org/10.1039/D1OB02401A
    98. Si-yu Tian, Shu-ming Chen, Cheng-xi Pan, Yong Li. FXR: structures, biology, and drug development for NASH and fibrosis diseases. Acta Pharmacologica Sinica 2022, 43 (5) , 1120-1132. https://doi.org/10.1038/s41401-021-00849-4
    99. John Y.L. Chiang, Jessica M. Ferrell. Discovery of farnesoid X receptor and its role in bile acid metabolism. Molecular and Cellular Endocrinology 2022, 548 , 111618. https://doi.org/10.1016/j.mce.2022.111618
    100. Ludovico Abenavoli, Anna Caterina Procopio, Pietro Cinaglia, Christian Zanza, Claudio Delle Grazie, Yaroslava Longhitano, Pavla Libicherova, Francesco Luzza. Clinical Patterns of Primary Biliary Cholangitis: Comparison Between Two European Case Series. Reviews on Recent Clinical Trials 2022, 17 (2) , 136-142. https://doi.org/10.2174/1574887117666220617095856
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