(+)-(4aS,8aS,10aR)-1,1,4a,8a-tetramethyl-2,6-dioxo-1,2,4a,6,7,8,8a,9,10,10a-decahydrophenanthrene-3-carbonitrile | 1029027-52-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (+)-(4aS,8aS,10aR)-1,1,4a,8a-tetramethyl-2,6-dioxo-1,2,4a,6,7,8,8a,9,10,10a-decahydrophenanthrene-3-carbonitrile
• 英文别名: (4aS,8aS,10aR)-1,1,4a,8a-tetramethyl-2,6-dioxo-8,9,10,10a-tetrahydro-7H-phenanthrene-3-carbonitrile
• CAS: 1029027-52-8
• 化学式: C₁₉H₂₃NO₂
• 分子量: 297.397
• InChiKey: GTWIHHXFFORGMI-KYNGSXCRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  57.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (+)-(4aS)-4,4a,5,6,7,8-hexahydro-1,4a-dimethyl-naphthalen-2(3H)-one 在 chromium(VI) oxide 、 甲醇 、 叔丁基过氧化氢 、 盐酸羟胺 、 氨 、 sodium methylate 、 lithium 、 sodium hydride 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 mineral oil 、 苯 为溶剂， 生成 (+)-(4aS,8aS,10aR)-1,1,4a,8a-tetramethyl-2,6-dioxo-1,2,4a,6,7,8,8a,9,10,10a-decahydrophenanthrene-3-carbonitrile
  参考文献：
  名称：

  Tricyclic Compounds Containing Nonenolizable Cyano Enones. A Novel Class of Highly Potent Anti-Inflammatory and Cytoprotective Agents

  摘要：

  Forty-four novel tricycles containing nonenolizable cyano enones (TCEs) were designed and synthesized on the basis of a semisynthetic pentacyclic triterpenoid, bardoxolone methyl, which is currently being developed in phase II clinical trials for the treatment of severe chronic kidney disease in diabetic patients. Most of the TCEs having two different kinds of nonenolizable cyano enones in rings A and C are highly potent suppressors of induction of inducible nitric oxide synthase stimulated with interferon-gamma and are highly potent inducers of the cytoprotective enzymes heme oxygenase-1 and NAD(P)H:quinone oxidoreductase-1. Among these compounds, (+/-)-(4bS,8aR,10aS)-10a-ethynyl-4b,8,8-trimethyl-3,7-dioxo-3,4b,7,8,8a,9,10,10a-octahydrophenanthrene-2,6-dicarbonitrile ((+/-)-31) is the most potent in these bioassays in our pool of drug candidates including semisynthetic triterpenoids and synthetic tricycles. These facts strongly suggest that an essential factor for potency is not a triterpenoid skeleton but the cyano enone functionality. Notably, TCE 31 reduces hepatic tumorigenesis induced with aflatoxin in rats. Further preclinical studies and detailed mechanism studies on 31 are in progress.

  DOI：

  10.1021/jm101445p

文献信息

• SYNTHETIC TRITERPENOIDS AND TRICYCLIC-BIS-ENONES FOR USE IN STIMULATING BONE AND CARTILAGE GROWTH
  申请人：Spoorn Michael B.

  公开号：US20080233195A1

  公开（公告）日：2008-09-25

  The present invention concerns methods for stimulating the growth and repair of bone and cartilage using synthetic triterpenoids and tricyclic-bis-enones. Examples of suitable triterpenoids include CDDO, CDDO-Me, CDDO-Im, and CDDO-Ethylamide. Examples of tricyclic-bis-enones include TBE-31 and TBE-34.

  本发明涉及使用合成三萜类化合物和三环双酮类化合物刺激骨骼和软骨生长和修复的方法。适用的三萜类化合物示例包括CDDO、CDDO-Me、CDDO-Im和CDDO-Ethylamide。适用的三环双酮类化合物示例包括TBE-31和TBE-34。
• TRICYCLIC-BIS-ENONE DERIVATIVES AND METHODS OF USE THEREOF
  申请人：Trustees of Dartmouth College

  公开号：EP1465615B1

  公开（公告）日：2012-08-01
• Tricyclic-Bis-Enone Derivatives and Methods of Use Thereof
  申请人：Honda Tadashi

  公开号：US20100261930A1

  公开（公告）日：2010-10-14

  Novel tricyclic-bis-enone derivatives (TBEs) as well as the process for the preparation of such TBEs are provided. Also provided are methods for prevention and/or treatment of cancer, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotropic lateral sclerosis, rheumatoid arthritis, inflammatory bowel disease, and all other diseases whose pathogenesis is believed to involve excessive production of either nitric oxide (NO) or prostaglandins or the overexpression of iNOS or COX-2 genes or gene products. Further, methods for the synthesis of the TBE compounds of the invention utilize cheap commercially available reagents and are highly cost effective and amenable to scale-up. Additional high efficiency synthetic methods that utilize novel intermediates as well as the synthesis of these intermediates are also provided. Furthermore, the invention also provides methods for designing novel and water-soluble TBEs.
• US7176237B2
  申请人：——

  公开号：US7176237B2

  公开（公告）日：2007-02-13
• US7678830B2
  申请人：——

  公开号：US7678830B2

  公开（公告）日：2010-03-16