Process Research and Impurity Control Strategy for Obeticholic Acid, a Farnesoid X Receptor Agonist

被引：4
|
作者：
Feng, Wei-Dong [1 ]
Zhuo, Song-Ming [2 ]
Zhang, Fu-Li [1 ,3 ]
机构：
[1] Zhejiang Univ Technol, Collaborat Innovat Ctr Yangtze River Delta Reg Gr, 18 Chaowang Rd, Hangzhou 310032, Zhejiang, Peoples R China
[2] China Pharmaceut Univ, Dept Pharmaceut Engn, 24 Tongjiaxiang, Nanjing 210009, Jiangsu, Peoples R China
[3] China State Inst Pharmaceut Ind, Shanghai Inst Pharmaceut Ind, 285 Gebaini Rd, Shanghai 201203, Peoples R China
来源：
ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2019年 / 23卷 / 09期
关键词：
obeticholic acid; process; primary biliary cholangitis; nonalcoholic steatohepatitis;
D O I：
10.1021/acs.oprd.9b00252
中图分类号：
O69 [应用化学];
学科分类号：
081704 ;
摘要：
The process to obtain ICH-grade quality obeticholic acid (OCA) was improved, and the overall yield was 25.9%. The critical process parameters were established to reduce or avoid process-related impurities. The formation mechanisms, purge pathways, and control strategies for these impurities were also discussed for the first time. An high-performance liquid chromatography instrument utilizing the charged aerosol detection technique was applied for an impurity content assay in OCA for the first time. The developed process was robust and suitable for manufacturing scale-up.
引用
收藏
页码：1979 / 1989
页数：11
相关论文
共 50 条
  • [31] Regulation of Intestinal UDP-Glucuronosyltransferase 1A1 by the Farnesoid X Receptor Agonist Obeticholic Acid Is Controlled by Constitutive Androstane Receptor through Intestinal Maturation
    Weber, Andre A.
    Mennillo, Elvira
    Yang, Xiaojing
    van der Schoor, Lori W. E.
    Jonker, Johan W.
    Chen, Shujuan
    Tukey, Robert H.
    DRUG METABOLISM AND DISPOSITION, 2021, 49 (01) : 12 - 19
  • [32] Suppression of Lung Nitrogen Mustard-induced Pulmonary Fibrosis, Oxidative Stress and Inflammatory Macrophage Activation by the Farnesoid X Receptor Agonist, Obeticholic Acid
    Meshanni, J.
    Sun, R.
    Vayas, K.
    Guo, G.
    Gow, A.
    Laskin, J.
    Laskin, D. L.
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2023, 207
  • [33] Correction: Synergistic tumor inhibition of colon cancer cells by nitazoxanide and obeticholic acid, a farnesoid X receptor ligand
    Junhui Yu
    Kui Yang
    Jianbao Zheng
    Wei Zhao
    Xuejun Sun
    Cancer Gene Therapy, 2022, 29 : 871 - 872
  • [34] The farnesoid X receptor agonist obeticholic acid upregulates biliary excretion of asymmetric dimethylarginine via MATE-1 during hepatic ischemia/reperfusion injury
    Ferrigno, Andrea
    Di Pasqua, Laura Giuseppina
    Berardo, Clarissa
    Siciliano, Veronica
    Rizzo, Vittoria
    Adorini, Luciano
    Richelmi, Plinio
    Vairetti, Mariapia
    PLOS ONE, 2018, 13 (01):
  • [35] LONG-TERM (LT) THERAPY OF A FARNESOID X RECEPTOR (FXR) AGONIST OBETICHOLIC ACID (OCA) MAINTAINS BIOCHEMICAL RESPONSE IN PRIMARY BILIARY CIRRHOSIS (PBC)
    Hirschfield, G.
    Kowdley, K.
    Mason, A.
    Luketic, V.
    Gordon, S.
    Vincent, C.
    Mayo, M.
    Pares, A.
    Chapman, R.
    Lindor, K.
    Esguerra, M.
    Eliot, L.
    Shapiro, D.
    JOURNAL OF HEPATOLOGY, 2012, 56 : S372 - S372
  • [36] THE FARNESOID X RECEPTOR (FXR) AGONIST OBETICHOLIC ACID (OCA) INCREASES PLASMA FGF-19 CONCENTRATIONS AND DECREASES BILE ACID SYNTHESIS IN PRIMARY BILIARY CIRRHOSIS (PBC)
    Marschall, H. -U.
    Luketic, V.
    Lovgren-Sandblom, A.
    Benthin, L.
    Kowdley, K.
    Hirschfield, G.
    Mason, A.
    Lindor, K.
    Gordon, S.
    Vincent, C.
    Chapman, R.
    Mayo, M.
    Burroughs, A.
    Pares, A.
    Jones, D.
    Schramm, C.
    Eliot, L.
    Hofmann, A. F.
    Shapiro, D.
    JOURNAL OF HEPATOLOGY, 2012, 56 : S377 - S377
  • [37] Extending the Structure-Activity Relationship of Anthranilic Acid Derivatives As Farnesoid X Receptor Modulators: Development of a Highly Potent Partial Farnesoid X Receptor Agonist
    Merk, Daniel
    Lamers, Christina
    Ahmad, Khalil
    Gomez, Roberto Carrasco
    Schneider, Gisbert
    Steinhilber, Dieter
    Schubert-Zsilavecz, Manfred
    JOURNAL OF MEDICINAL CHEMISTRY, 2014, 57 (19) : 8035 - 8055
  • [38] Obeticholic acid aggravates liver fibrosis by activating hepatic farnesoid X receptor-induced apoptosis in cholestatic mice
    Lu, Qian
    Yu, Jingyi
    Xia, Ninglin
    Jin, Ming
    Zhao, Wen
    Fan, Xue
    Zhang, Rongmi
    Wang, Jie
    Jiang, Zhenzhou
    Yu, Qinwei
    CHEMICO-BIOLOGICAL INTERACTIONS, 2025, 406
  • [39] Farnesoid X Receptor (FXR) Agonist Obeticholic Acid (OCA) Restores Liver Regeneration after Partial Hepatectomy in Bile Acid Deprived Rats but Does Not Overdrive Natural FXR Activation in the Physiologic Process of Liver Regeneration.
    Dahrenmoller, Carola
    Schaap, Frank G.
    Damink, Steven Olde, Sr.
    Van Mierlo, Kim
    Jansen, Peter L. M.
    Horsmans, Yves
    Leclercq, Isabelle A.
    HEPATOLOGY, 2018, 68 : 827A - 828A
  • [40] THE FARNESOID X RECEPTOR AGONIST, OBETICHOLIC ACID, IMPROVES INTESTINAL ANTIBACTERIAL DEFENSE AND REDUCES GUT BACTERIAL TRANSLOCATION AND HEPATIC FIBROGENESIS IN CCl4-CIRRHOTIC RATS WITH ASCITES
    Ubeda, M.
    Borrero, M. J.
    Lario, M.
    Munoz, L.
    Conde, E.
    Rodriguez, M.
    LLedo, L.
    Garcia-Bermejo, L.
    Alvarez-Mon, M.
    Albillos, A.
    JOURNAL OF HEPATOLOGY, 2014, 60 (01) : S63 - S63
12345