3-ethyl-3-ethynyl-6-oxocyclohexa-1,4-dienecarbonitrile | 1207111-94-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-ethyl-3-ethynyl-6-oxocyclohexa-1,4-dienecarbonitrile
• 英文别名: 3-Ethyl-3-ethynyl-6-oxocyclohexa-1,4-diene-1-carbonitrile
• CAS: 1207111-94-1
• 化学式: C₁₁H₉NO
• 分子量: 171.199
• InChiKey: JHHWHLBJYCYYAA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  40.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  5-ethyl-5-ethynyl-2-oxocyclohex-3-enecarbonitrile 在 吡啶 、 苯基氯化硒 、 双氧水 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 1.5h， 以79%的产率得到3-ethyl-3-ethynyl-6-oxocyclohexa-1,4-dienecarbonitrile
  参考文献：
  名称：

  New Monocyclic, Bicyclic, and Tricyclic Ethynylcyanodienones as Activators of the Keap1/Nrf2/ARE Pathway and Inhibitors of Inducible Nitric Oxide Synthase

  摘要：

  A monocyclic compound 3 (3-ethynyl-3-methyl-6-oxocyclohexa-1,4-dienecarbonitrile) is a highly reactive Michael acceptor leading to reversible adducts with nucleophiles, which displays equal or greater potency than the pentacyclic triterpenoid CDDO in inflammation and carcinogenesis related assays. Recently, reversible covalent drugs, which bind with protein targets but not permanently, have been gaining attention because of their unique features. To explore such reversible covalent drugs, we have synthesized monocyclic, bicyclic, and tricyclic compounds containing 3 as an electrophilic fragment and evaluated them as activators of the Keap1/Nrf2/ARE pathway and inhibitors of iNOS. Notably, these compounds maintain the unique features of the chemical reactivity and biological potency of 3. Among them, a monocyclic compound 5 is the most potent in these assays while a tricyclic compound 14 displays a more robust and specific activation profile compared to 5. In conclusion, we demonstrate that 3 is a useful electrophilic fragment for exploring reversible covalent drugs.

  DOI：

  10.1021/acs.jmedchem.5b00393

文献信息

• MONOCYCLIC CYANOENONES AND METHODS OF USE THEREOF
  申请人：Honda Tadashi

  公开号：US20110196007A1

  公开（公告）日：2011-08-11

  The present invention features monocyclic cyanoenone compositions and methods for using the same in the treatment of diseases such as cancer, inflammatory diseases and neurodegenerative diseases.

  本发明涉及单环氰基烯酮组合物及其在治疗癌症、炎症性疾病和神经退行性疾病等疾病中的应用方法。
• Acetylenic cyanoenones as therapeutics for inflammation and carcinogenesis
  申请人：Honda Tadashi

  公开号：US10233146B2

  公开（公告）日：2019-03-19

  The present invention provides a compound having the structure: wherein X is C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, cyano, aryl, heteroaryl, alkylaryl, alkylheteroaryl, alkenylaryl, alkenylheteroaryl, alkynylaryl, alkynylheteroaryl, alkoxy, alkenyloxy, alkynyloxy, aryloxy, heteroaryloxy, acyl, alkylhydroxy, alkylamino, alkenylamino, alkynylamino, amido, carboxyl, or carboxyl ester, or forms an unsubstituted or substituted cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, indane or tetralin with Y, Y is H or forms an unsubstituted or substituted cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, indane or tetralin with X, or forms an unsubstituted or substituted monocycle with Z; and Z is H or forms an unsubstituted or substituted monocycle with Y; wherein when X and Y are both H, then X is C2 alkenyl or C2 alkynyl, and when Y is H forms a substituted cyclohexyl, cycloheptyl with X, the cyclohexyl is other than a trisubstituted cyclohexyl bearing CH3, i-Pr and (CH2)2CO2CH3 groups or CH3, i-Pr and (CH2)3NH2, or a salt or ester thereof.

  本发明提供了一种具有以下结构的化合物： 其中 X是C1-C12烷基、C2-C12烯基、C2-C12炔基、氰基、芳基、杂芳基、烷芳基、烷基异芳基、烯芳基、烯基异芳基、炔芳基、炔基异芳基、烷氧基、烯氧基、炔氧基、芳氧基、杂芳氧基、酰基、烷基羟基、烷基氨基、烯基氨基、炔基氨基、氨基、羧基或羧基酯，或与 Y 形成未取代或取代的环丁基、环戊基、环己基、环庚基、茚或四萘、 Y 是 H，或与 X 形成未取代或取代的环丁基、环戊基、环己基、环庚基、茚满或四萘，或与 Z 形成未取代或取代的单环；和 Z 是 H，或与 Y 形成未取代或取代的单环； 其中，当 X 和 Y 均为 H 时，则 X 为 C2 烯基或 C2 炔基，而当 Y 为 H 时，则与 X 形成取代的环己基、环庚基，该环己基是三取代的环己基以外的环己基。 当 Y 为 H 与 X 形成取代的环己基、环庚基时，环己基不是含有 CH3、i-Pr 和 (CH2)2CO2 基团或 、i-Pr 和 ( )3NH2 的三取代环己基、 或其盐或酯。
• ACETYLENIC CYANOENONES AS THERAPEUTICS FOR INFLAMMATION AND CARCINOGENESIS
  申请人：Honda Tadashi

  公开号：US20180134654A1

  公开（公告）日：2018-05-17

  The present invention provides a compound having the structure: wherein X is C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, cyano, aryl, heteroaryl, alkylaryl, alkylheteroaryl, alkenylaryl, alkenylheteroaryl, alkynylaryl, alkynylheteroaryl, alkoxy, alkenyloxy, alkynyloxy, aryloxy, heteroaryloxy, acyl, alkylhydroxy, alkylamino, alkenylamino, alkynylamino, amido, carboxyl, or carboxyl ester, or forms an unsubstituted or substituted cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, indane or tetralin with Y, Y is H or forms an unsubstituted or substituted cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, indane or tetralin with X, or forms an unsubstituted or substituted monocycle with Z; and Z is H or forms an unsubstituted or substituted monocycle with Y; wherein when X and Y are both H, then X is C 2 alkenyl or C 2 alkynyl, and when Y is H forms a substituted cyclohexyl, cycloheptyl with X, the cyclohexyl is other than a trisubstituted cyclohexyl bearing CH 3 , i-Pr and (CH 2 ) 2 CO 2 CH 3 groups or CH 3 , i-Pr and (CH 2 ) 3 NH 2 , or a salt or ester thereof.
• US8314137B2
  申请人：——

  公开号：US8314137B2

  公开（公告）日：2012-11-20
• US9000188B2
  申请人：——

  公开号：US9000188B2

  公开（公告）日：2015-04-07