Design, synthesis, and biological activity of second-generation synthetic oleanane triterpenoids

被引：14
作者：
Fu, Liangfeng [1 ]
Lin, Qi-xian [1 ]
Onyango, Evans O. [1 ]
Liby, Karen T. [2 ]
Sporn, Michael B. [2 ]
Gribble, Gordon W. [1 ]
机构：
[1] Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA
[2] Geisel Sch Med, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA
来源：
ORGANIC & BIOMOLECULAR CHEMISTRY | 2017年 / 15卷 / 28期
关键词：
CHRONIC KIDNEY-DISEASE; CDDO-METHYL ESTER; TRANSGENIC MOUSE MODEL; BARDOXOLONE-METHYL; ETHYL AMIDE; CANCER; MECHANISM; MICE; PREVENTION; PATHWAY;
D O I：
10.1039/c7ob01420a
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
We report the synthesis and biological activity of C-24 demethyl CDDO-Me 2 and the C-28 amide derivatives 3 and 4, which are analogues of the anti-inflammatory synthetic triterpenoid bardoxolone methyl (CDDO-Me) 1. Demethylation of the C-24 methyl group was accomplished via "abnormal Beckmann" rearrangement and subsequent ring A reformation. Amides 3 and 4 were found to be potent inhibitors of the production of the inflammatory mediator NO in vitro.
引用
收藏
页码：6001 / 6005
页数：5
相关论文
共 33 条
[1]   CDDO-Me Redirects Activation of Breast Tumor Associated Macrophages [J].
Ball, Michael S. ;
Shipman, Emilie P. ;
Kim, Hyunjung ;
Liby, Karen T. ;
Pioli, Patricia A. .
PLOS ONE, 2016, 11 (02)
[2]   Is B-type Natriuretic Peptide a Risk Factor for Heart Failure in Patients Treated With Bardoxolone Methyl? [J].
Camer, Danielle ;
Huang, Xu-Feng .
JOURNAL OF CARDIAC FAILURE, 2015, 21 (03) :258-259
[3]   The Endothelin Pathway: A Protective or Detrimental Target of Bardoxolone Methyl on Cardiac Function in Patients with Advanced Chronic Kidney Disease? [J].
Camer, Danielle ;
Huang, Xu-Feng .
AMERICAN JOURNAL OF NEPHROLOGY, 2014, 40 (03) :288-290
[4]   Total synthesis of (-)-elegansidiol by using an abnormal Beckmann fragmentation of Hajos ketone oxime as a key step [J].
Cao, Liya ;
Sun, Jianwei ;
Wang, Xinyan ;
Zhu, Rui ;
Shi, Haijian ;
Hu, Yuefei .
TETRAHEDRON, 2007, 63 (23) :5036-5041
[5]   2-cyano-3,12-dioxooleana-1,9(11)-diene-28-oic acid disrupts microtubule polymerization: A possible mechanism contributing to apoptosis [J].
Couch, RD ;
Ganem, NJ ;
Zhou, M ;
Popov, VM ;
Honda, T ;
Veenstra, TD ;
Sporn, MB ;
Anderson, AC .
MOLECULAR PHARMACOLOGY, 2006, 69 (04) :1158-1165
[6]   Studies on the reactivity of CDDO, a promising new chemopreventive and chemotherapeutic agent: implications for a molecular mechanism of action [J].
Couch, RD ;
Browning, RG ;
Honda, T ;
Gribble, GW ;
Wright, DL ;
Sporn, MB ;
Anderson, AC .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (09) :2215-2219
[7]   Bardoxolone Methyl in Type 2 Diabetes and Stage 4 Chronic Kidney Disease [J].
de Zeeuw, Dick ;
Akizawa, Tadao ;
Audhya, Paul ;
Bakris, George L. ;
Chin, Melanie ;
Christ-Schmidt, Heidi ;
Goldsberry, Angie ;
Houser, Mark ;
Krauth, Melissa ;
Heerspink, Hiddo J. Lambers ;
McMurray, John J. ;
Meyer, Colin J. ;
Parving, Hans-Henrik ;
Remuzzi, Giuseppe ;
Toto, Robert D. ;
Vaziri, Nosratola D. ;
Wanner, Christoph ;
Wittes, Janet ;
Wrolstad, Danielle ;
Chertow, Glenn M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (26) :2492-2503
[8]   Bardoxolone Methyl Prevents High-Fat Diet-Induced Colon Inflammation in Mice [J].
Dinh, Chi H. L. ;
Yu, Yinghua ;
Szabo, Alexander ;
Zhang, Qingsheng ;
Zhang, Peng ;
Huang, Xu-Feng .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2016, 64 (04) :237-255
[9]   The synthetic triterpenoid (CDDO-Im) inhibits STAT3, as well as IL-17, and improves DSS-induced colitis in mice [J].
Fitzpatrick, Leo R. ;
Stonesifer, Elizabeth ;
Small, Jeffrey S. ;
Liby, Karen T. .
INFLAMMOPHARMACOLOGY, 2014, 22 (06) :341-349
[10]   Efficient and Scalable Synthesis of Bardoxolone Methyl (CDDO-methyl Ester) [J].
Fu, Liangfeng ;
Gribble, Gordon W. .
ORGANIC LETTERS, 2013, 15 (07) :1622-1625
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