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公开(公告)号:US06974801B2
公开(公告)日:2005-12-13
申请号:US10435925
申请日:2003-05-12
申请人: Tadashi Honda , Yukiko Honda , Gordon W. Gribble , Michael B. Sporn , Nanjoo Suh
发明人: Tadashi Honda , Yukiko Honda , Gordon W. Gribble , Michael B. Sporn , Nanjoo Suh
IPC分类号: A61K31/275 , A61K31/4172 , A61K31/4184 , A61K31/4196 , A61K31/704 , C07D233/54 , C07D233/60 , C07D233/68 , C07D235/06 , C07D249/08 , C07D249/10 , C07D317/34 , C07H15/24 , A61K31/70 , A61K31/4164 , C07H13/08
CPC分类号: C07D233/54 , A61K31/275 , A61K31/4172 , A61K31/4184 , A61K31/4196 , A61K31/704 , C07D233/68 , C07D235/06 , C07D249/08 , C07D317/34 , C07H15/24
摘要: New triterpenoid derivatives with various substituents at the C-17 position of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) were synthesized. Among them, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile (CNDDO), 1-(2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl) imidazole, 1-(2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl)-2-methylimidazole, 1-(2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl)-4-methylimidazole show extremely high inhibitory activity (IC50=0.01-1 pM level) against production of nitric oxide induced by interferon-γ in mouse macrophages. These compounds can be used in the prevention or treatment of diseases such as cancer, Alzheimer's disease, Parkinson's disease, multiple sclerosis, rheumatoid arthritis, and other inflammatory diseases. All the new triterpenoid derivatives are more potent than previously known CDDO.
摘要翻译: 合成了在2-氰基-3,12-二氧代噻吩-1,9(11) - 二 - 二十八酸(CDDO)的C-17位具有各种取代基的新三萜衍生物。 其中,2-氰基-3,12-二氧代噻吩-1,9(11) - 二烯-28-腈(CNDDO),1-(2-氰基-3,12-二氧杂环戊烯-1,9(11) - 二烯 -2-甲基咪唑,1-(2-氰基-3,12-二氧杂环戊烯-1,9(11) - 二烯-28-基)-2-甲基咪唑,1-(2-氰基-3,12-二氧代噻唑 -1,9(11) - 二烯-28-基)-4-甲基咪唑显示出对干扰素-γ诱导的一氧化氮产生的极高的抑制活性(IC 50> 0.01-1pM水平) 在小鼠巨噬细胞。 这些化合物可用于预防或治疗诸如癌症,阿尔茨海默氏病,帕金森病,多发性硬化症,类风湿性关节炎和其它炎性疾病的疾病。 所有新的三萜衍生物比先前已知的CDDO更有效。