(E)-4-(3-(dimethylamino)acryloyl)-N,N-dimethylbenzamide | 1008119-10-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-4-(3-(dimethylamino)acryloyl)-N,N-dimethylbenzamide
• 英文别名: 4-[(E)-3-(dimethylamino)prop-2-enoyl]-N,N-dimethylbenzamide
• CAS: 1008119-10-5
• 化学式: C₁₄H₁₈N₂O₂
• 分子量: 246.309
• InChiKey: BCXJSQWZMQMQAI-MDZDMXLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-4-(3-(dimethylamino)acryloyl)-N,N-dimethylbenzamide 在 sodium tetrahydroborate 、 四氯化钛 、 溶剂黄146 、 lithium chloride 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.5h， 生成 2-[5-Chloro-13-[4-(dimethylcarbamoyl)phenyl]-2-oxa-4,14-diazatricyclo[8.4.0.03,8]tetradeca-1(10),3(8),4,6,11,13-hexaen-9-yl]-2-methylpropanoic acid
  参考文献：
  名称：

  [EN] FUSED HETEROARYL MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-KB ACTIVITY AND USE THEREOF
  [FR] MODULATEURS HÉTÉROARYLE CONDENSÉS, DE L'ACTIVITÉ AP-1 ET/OU NF-?B DU RÉCEPTEUR DES GLUCOCORTICOÏDES ET LEUR UTILISATION

  摘要：

  提供了一种新型的非类固醇化合物，可用于治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病或紊乱，包括代谢性、炎症性和免疫性疾病或紊乱，其结构如下式（I）：其对映体、非对映体或互变异构体，或其前药酯，或其药用可接受盐，其中：Z是杂环或杂芳基；• A是S至8-成员碳环或S至8-成员杂环；B1和B2环是吡啶环，其中B1和B2环各与A环融合，B1环可选地由一个至三个基取代，所述基相同或不同，并且独立地从R1、R2和R4中选择，B2环可选地由一个至三个基取代，所述基相同或不同，并且独立地从R5、R7和R3中选择，J1、J2和J3在每次出现时相同或不同，并且独立地为-A1QA2-；Q是键，O，S，S（O）或S（O）2；A1和A2相同或不同，并且在每次出现时独立地从键，C1-3烷基，取代C1-3烷基，C2-4烯烃基和取代C2-4烯烃基中选择，前提是选择A1和A2以使环A为5-至8-成员碳环或杂环；R1至R11如此处所定义...

  公开号：

  WO2009100171A1
• 作为产物：
  描述：

  4-乙酰基苯甲酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 水 、 乙腈 为溶剂， 反应 30.0h， 生成 (E)-4-(3-(dimethylamino)acryloyl)-N,N-dimethylbenzamide
  参考文献：
  名称：

  [EN] FUSED HETEROARYL MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-KB ACTIVITY AND USE THEREOF
  [FR] MODULATEURS HÉTÉROARYLE CONDENSÉS, DE L'ACTIVITÉ AP-1 ET/OU NF-?B DU RÉCEPTEUR DES GLUCOCORTICOÏDES ET LEUR UTILISATION

  摘要：

  提供了一种新型的非类固醇化合物，可用于治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病或紊乱，包括代谢性、炎症性和免疫性疾病或紊乱，其结构如下式（I）：其对映体、非对映体或互变异构体，或其前药酯，或其药用可接受盐，其中：Z是杂环或杂芳基；• A是S至8-成员碳环或S至8-成员杂环；B1和B2环是吡啶环，其中B1和B2环各与A环融合，B1环可选地由一个至三个基取代，所述基相同或不同，并且独立地从R1、R2和R4中选择，B2环可选地由一个至三个基取代，所述基相同或不同，并且独立地从R5、R7和R3中选择，J1、J2和J3在每次出现时相同或不同，并且独立地为-A1QA2-；Q是键，O，S，S（O）或S（O）2；A1和A2相同或不同，并且在每次出现时独立地从键，C1-3烷基，取代C1-3烷基，C2-4烯烃基和取代C2-4烯烃基中选择，前提是选择A1和A2以使环A为5-至8-成员碳环或杂环；R1至R11如此处所定义...

  公开号：

  WO2009100171A1

文献信息

• MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-kB ACTIVITY AND USE THEREOF
  申请人：Weinstein David S.

  公开号：US20090075995A1

  公开（公告）日：2009-03-19

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including inflammatory and immune diseases, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which: Z is heterocyclo or heteroaryl; A is a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring; B is a cycloalkyl, cycloalkenyl, aryl, heterocyclo, or heteroaryl ring, wherein each ring is fused to the A ring on adjacent atoms and optionally substituted by one to four groups which are the same or different and are independently selected from R 5 , R 6 , R 7 , and R 8 ; J 1 , J 2 , and J 3 are at each occurrence the same or different and are independently -A 1 QA 2 -; Q is a bond, O, S, S(O), or S(O) 2 ; A 1 and A 2 are the same or different and are at each occurrence independently selected from a bond, C 1-3 alkylene, substituted C 1-3 alkylene, C 2-4 alkenylene, and substituted C 2-4 alkenylene, provided that A 1 and A 2 are chosen so that ring A is a 5- to 8-membered carbocyclic or heterocyclic ring; R 1 to R 11 are as defined herein. Also provided are pharmaceutical compositions and methods of treating inflammatory- or immune-associated diseases and obesity and diabetes employing said compounds.

  提供了一系列新颖的非甾体化合物，这些化合物在治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病中很有用，包括炎性和免疫疾病，具有以下结构式（I）： 其对应的光学异构体、对映异构体或互变异构体，或其前药酯，或其药用可接受盐，其中： Z是杂环或杂芳基； A是一个5至8成员的碳环或一个5至8成员的杂环； B是一个环烷基、环烯基、芳基、杂环或杂芳基环，其中每个环都与A环上的相邻原子融合，并且可以选择性地被一个到四个独立选自R5、R6、R7和R8的相同或不同的组取代； J1、J2和J3每次出现时相同或不同，独立地选自-A1QA2-；Q是键、O、S、S(O)或S(O)2；A1和A2相同或不同，每次出现时独立地选自键、C1-3烷基、取代的C1-3烷基、C2-4烯基和取代的C2-4烯基，前提是A1和A2的选择使得环A是一个5至8成员的碳环或杂环； R1至R11如本文所述定义。 还提供了使用这些化合物的药物组合物和治疗炎性疾病、免疫相关疾病、肥胖和糖尿病的方法。
• Fused heteroaryl modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof
  申请人：Bristol-Myers Squibb Company

  公开号：US08304539B2

  公开（公告）日：2012-11-06

  Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or taυtomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which: Z is heterocyclo or heteroaryl; •A is a S- to 8-membered carbocyclic ring or a S- to 8-membered heterocyclic ring; B1 and B2 rings are pyridyl rings, wherein the B1 and B2 rings are each fused to the A ring and the B1 ring is optionally substituted by one to three groups which are the same or different and are independently selected from R1, R2, and R4, and the B2 ring is optionally substituted by one to three groups which are the same or different and are independently selected from R5, R7, and R3 J1, J2, and J3 are at each occurrence the same or different and are independently -A1QA2-; Q is a bond, O, S, S(O), or S(O)2; A1 and A2 are the same or different and are at each occurrence independently selected from a bond, C1-3 alkylene, substituted C1-3 alkylene, C2-4 alkenylene, and substituted C2-4 alkenylene, provided that A1 and A2 are chosen so that ring A is a 5- to 8-membered carbocyclic or heterocyclic ring; R1 to R11 are as defined herein.

  提供了新型非甾体化合物，其在治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病或障碍中非常有用，包括代谢性、炎症性和免疫性疾病或障碍，其结构为公式（I）：其对映体、顺异构体或互变异构体，或其前药酯，或其药学上可接受的盐，其中：Z是杂环或杂芳基；•A是S-至8元环碳环或S-至8元杂环；B1和B2环是吡啶环，其中B1和B2环各与A环融合，B1环可选地被一到三个相同或不同的基团取代，这些基团独立地从R1、R2和R4中选择，B2环可选地被一到三个相同或不同的基团取代，这些基团独立地从R5、R7和R3 J1、J2和J3在每次出现时都相同或不同，并且独立地是-A1QA2-；Q是键，O，S，S（O）或S（O）2；A1和A2在每次出现时相同或不同，并且独立地从键，C1-3烷基，取代C1-3烷基，C2-4烯基和取代C2-4烯基中选择，前提是A1和A2被选择为环A是5-至8元环碳环或杂环；R1至R11如本文所定义。
• Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof
  申请人：Bristol-Myers Squibb Company

  公开号：US08034940B2

  公开（公告）日：2011-10-11

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including inflammatory and immune diseases, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which: Z is heterocyclo or heteroaryl; A is a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring; B is a cycloalkyl, cycloalkenyl, aryl, heterocyclo, or heteroaryl ring, wherein each ring is fused to the A ring on adjacent atoms and optionally substituted by one to four groups which are the same or different and are independently selected from R5, R6, R7, and R8; J1, J2, and J3 are at each occurrence the same or different and are independently -A1QA2-; Q is a bond, O, S, S(O), or S(O)2; A1 and A2 are the same or different and are at each occurrence independently selected from a bond, C1-3alkylene, substituted C1-3alkylene, C2-4alkenylene, and substituted C2-4alkenylene, provided that A1 and A2 are chosen so that ring A is a 5- to 8-membered carbocyclic or heterocyclic ring; R1 to R11 are as defined herein. Also provided are pharmaceutical compositions and methods of treating inflammatory- or immune-associated diseases and obesity and diabetes employing said compounds.

  提供了新型非甾体化合物，其在治疗与葡萄糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病方面具有用途，包括炎症和免疫疾病，其具有以下结构（I）的构造： 其中，Z是杂环或杂环芳基；A是5-至8-成员的碳环或5-至8-成员的杂环；B是环烷基，环烯基，芳基，杂环芳基或杂环，其中每个环在相邻原子上与A环融合，并且可选地被一个到四个相同或不同的基团取代，这些基团是独立地从R5、R6、R7和R8中选择的；J1、J2和J3在每次出现时相同或不同，并且独立地是-A1QA2-；Q是键，O，S，S（O）或S（O）2；A1和A2在每次出现时相同或不同，并且独立地从键，C1-3烷基，取代的C1-3烷基，C2-4烯基和取代的C2-4烯基中选择，前提是A1和A2被选择为环A是5-至8-成员的碳环或杂环；R1到R11如本文所定义。 还提供了制药组合物和使用所述化合物治疗炎症或免疫相关疾病以及肥胖症和糖尿病的方法。
• FUSED HETEROARYL MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-kappaB ACTIVITY AND USE THEREOF
  申请人：Duan Jingwu

  公开号：US20110002952A1

  公开（公告）日：2011-01-06

  Novel non-steroidal compounds are provided which are useful in treating diseases or disorders associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including metabolic and inflammatory and immune diseases or disorders, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which: Z is heterocyclo or heteroaryl; -A is a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring; B1 and B2 rings are pyridyl rings, wherein the B1 and B 2 rings are each fused to the A ring and the B1 ring is optionally substituted by one to three groups which are the same or different and are independently selected from R 1 , R 2 , and R 4 , and the B2 ring is optionally substituted by one to three groups which are the same or different and are independently selected from R3, R 7 , and R 3 71, J 2 , and J3 are at each occurrence the same or different and are independently -AIQA2-; Q is a bond, O, S, S(0), or S(O)2; A1 and A2 are the same or different and are at each occurrence independently selected from a bond, C1-3 alkylene, substituted C 1-3 alkylene, C24 alkenylene, and substituted C24 alkenylene, provided that A 1 and A2 are chosen so that ring A is a 5- to 8-membered carbocyclic or heterocyclic ring; R 1 to R 11 are as defined herein.

  提供了一种新型的非类固醇化合物，其在治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病或疾病中具有用途，包括代谢性、炎症和免疫性疾病或疾病，其具有以下结构（I）的对映体、顺反异构体或互变异构体，或其前药酯，或其药学上可接受的盐，其中：Z是杂环或杂环芳基；-A是5-至8-成员的碳环或5-至8-成员的杂环；B1和B2环是吡啶环，其中B1和B2环各与A环融合，B1环可选地被1至3个基取代，所述基是相同或不同的，且独立地从R1、R2和R4中选择，B2环可选地被1至3个基取代，所述基是相同或不同的，且独立地从R3、R7和R371、J2和J3中选择，每次出现时，J2和J3是相同或不同的，且独立地为-AIQA2-；Q是键，O、S、S（0）或S（O）2；A1和A2是相同或不同的，且每次出现时独立地从键、C1-3烷基、取代C1-3烷基、C24烯基和取代C24烯基中选择，前提是A1和A2被选择为环A是5-至8-成员的碳环或杂环；R1至R11如本文所定义。
• MODULATORS OF GLUCOCORTICOID RECEPTOR, AND/OR AP-1, AND/OR NF-KB ACTIVITY AND USE THEREOF
  申请人：Bristol-Myers Squibb Company

  公开号：EP2049507A2

  公开（公告）日：2009-04-22