(+)-(4aS,8aR)-(4aβ,8aβ)-4,4a,6,7,8,8a,9,10-octahydro-1,4a,8a-trimethylphenanthren-2(3H)-one | 670246-58-9

• 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,8aR)-(4aβ,8aβ)-4,4a,6,7,8,8a,9,10-octahydro-1,4a,8a-trimethylphenanthren-2(3H)-one
• 英文别名: (+)-(4aS,8aR)-1,4a,8a-trimethyl-4,4a,6,7,8,8a,9,10-octahydrophenanthren-2(3H)-one；(4aS,8aR)-1,4a,8a-triMethyl-4,4a,6,7,8,8a,9,10-octahydrophenanthren-2(3H)-one；(4aS,8aR)-1,4a,8a-trimethyl-4,6,7,8,9,10-hexahydro-3H-phenanthren-2-one
• CAS: 670246-58-9
• 化学式: C₁₇H₂₄O
• 分子量: 244.377
• InChiKey: FAYHTWDDMCBTHR-SJORKVTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (+)-(4aS,8aR)-(4aβ,8aβ)-4,4a,6,7,8,8a,9,10-octahydro-1,4a,8a-trimethylphenanthren-2(3H)-one 在 盐酸羟胺 、 氨 、 sodium methylate 、 lithium 作用下， 以 四氢呋喃 、 乙醇 、 水 、 苯 为溶剂， 生成 (+)-(4aS,8aR,10aR)-1,1,4a,8a-tetramethyl-3,4,4a,6,7,8,8a,9,10,10a-decahydrophenanthreno[3,2-d]isoxazole
  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
• 作为产物：
  描述：

  1-氯-3-戊酮 、 (-)-1,10-dimethyl-1(9)-octalone-2 在 sodium hydride 、 氢氧化钾 作用下， 以 四氢呋喃 、 甲醇 、 二甲基亚砜 为溶剂， 反应 17.0h， 以3.59 g的产率得到(+)-(4aS,8aR)-(4aβ,8aβ)-4,4a,6,7,8,8a,9,10-octahydro-1,4a,8a-trimethylphenanthren-2(3H)-one
  参考文献：
  名称：

  在环A和C中高效合成具有烯酮功能的（-）-和（+）-三环化合物。一类新型的口服活性抗炎和癌症化学预防剂。

  摘要：

  根据合成的三萜类化合物2-氰基-3,12-二氧代油酸酯-1,9（11）的结构设计了在环A和环C具有烯酮官能团的新型三环化合物[三环-双-烯酮（TBE）化合物]。 ）-二烯-28-油酸（CDDO）（1），它是预防和/或治疗癌症和炎症性疾病的有前途的候选药物，其发病机理可能涉及一氧化氮（NO）和/或前列腺素的过量生产。一系列外消旋形式的TBE化合物显示出对小鼠巨噬细胞中干扰素-γ（IFN-γ）诱导的NO产生的高抑制活性。这些化合物之一，（+/-）-（4a [小β，8a [小β，10a [小α]）-1,2,4a，6,8a，9,10,10a-八氢-1 ，1,4a，8a-tetramethyl-2,6-dioxophenanthren e-3,7-dicarbonitrile（（+/-）-3），在一项初步研究中，使用硫代乙醇酸酯和IFN-γ诱导的小鼠腹膜炎症，口服活性为15 mg kg（-1）（单次

  DOI：

  10.1039/b307491a

文献信息

• 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
• US8067465B2
  申请人：——

  公开号：US8067465B2

  公开（公告）日：2011-11-29