ethyl α-(5-chloro-6-methyl-1-oxo-2,3-dihydro-1H-inden-2-yl)-α-oxo-acetate | 919078-02-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: ethyl α-(5-chloro-6-methyl-1-oxo-2,3-dihydro-1H-inden-2-yl)-α-oxo-acetate
• 英文别名: ethyl 2-(5-chloro-6-methyl-1-oxo-2,3-dihydro-1H-inden-2-yl)-2-oxoacetate；Ethyl 2-(6-chloro-5-methyl-3-oxo-1,2-dihydroinden-2-yl)-2-oxoacetate
• CAS: 919078-02-7
• 化学式: C₁₄H₁₃ClO₄
• 分子量: 280.708
• InChiKey: IFVIQQJKXWTTRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl α-(5-chloro-6-methyl-1-oxo-2,3-dihydro-1H-inden-2-yl)-α-oxo-acetate 在 氢氧化钾 、 1-羟基苯并三唑 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 32.0h， 生成 6-chloro-1-(2’,4’-dichlorophenyl)-7-methyl-N-piperidin-1-yl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide
  参考文献：
  名称：

  Tricyclic Pyrazoles. 4. Synthesis and Biological Evaluation of Analogues of the Robust and Selective CB₂ Cannabinoid Ligand 1-(2‘,4‘-Dichlorophenyl)-6-methyl-N-piperidin-1-yl- 1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide

  摘要：

  New analogues (2a-p) of the previously reported CB2 ligands 6-methyl- and 6-chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamides (1a,b) have been synthesized and evaluated for cannabinoid receptor affinity. One example, 1-(2',4'-dichlorophenyl)-6-methyl-N-cyclohexyilamine-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide (2a) was shown to have single digit nanomolar affinity for cannabinoid CB2 receptors. Furthermore, compounds 2a and 2b, as well as lead structures 1a, b, were also shown to be agonist in an in vitro model based on human promyelocytic leukemia HL-60 cells.

  DOI：

  10.1021/jm060920d
• 作为产物：
  描述：

  5-氯-6-甲基-1-茚酮 以87%的产率得到ethyl α-(5-chloro-6-methyl-1-oxo-2,3-dihydro-1H-inden-2-yl)-α-oxo-acetate
  参考文献：
  名称：

  PHARMACEUTICAL COMPOUNDS

  摘要：

  具有紧凑结构的三环化合物，包含一个苯环和一个吡唑环，通过一个由五至八个原子组成的中心环相互连接，在CB1和/或CB2受体上具有亲和力，具有中枢神经系统和/或外周活性，化学式（I）如下：其中各种取代基如描述中所定义。这些化合物对CB1和/或CB2类大麻素受体具有亲和力。

  公开号：

  US20100215741A1

文献信息

• PHARMACEUTICAL COMPOSITIONS
  申请人：LAZZARI Paolo

  公开号：US20100216785A1

  公开（公告）日：2010-08-26

  Microemulsions of pharmaceutical compositions comprising, the following components (% by weight), the sum of the components being 100%: S) from 0.01 to 95% of one or more compounds selected from surfactants, polymers, forming organized structures as: aggregates, micelles, liquid crystals, vesicles, in the liquid in which they are solubilized, O) from 0.01 to 95% of one or more oils selected from esters of C 4 -C 32 acids or C 4 -C 32 acids, PA) from 0.001 to 90% of compounds having affinity for the CB1 and/or CB2 cannabinoidergic receptors of formula A′: AD) from 0 to 60% by weight of one or more compounds selected from modifiers of the water and/or oil polarity, modifiers of the film curvature of component S), co-surfactants, water or a saline aqueous solution the difference to 100%, wherein the ratio by weight S)/PA) is lower than that of microemulsions wherein component O) is absent.

  药物组成的微乳液包含以下组分（按重量百分比计算），各组分总和为100％：S）从0.01到95％的一种或多种化合物，选自表面活性剂、聚合物，形成有序结构，如：聚集体、胶束、液晶、囊泡，在它们被溶解的液体中，O）从0.01到95％的一种或多种油，选自C4-C32酸酯或C4-C32酸，PA）从0.001到90％的化合物，具有亲和力为公式A'的CB1和/或CB2大麻素受体，AD）从0到60％的一种或多种化合物，按重量计算，选自调节剂，水和/或油极性的调节剂，组分S）的膜曲率调节剂，共表面活性剂，水或盐水溶液之差为100％，其中按重量比S）/PA）低于不含组分O）的微乳液的比例。
• Tricyclic condensed pyrazole derivatives as CB1 inhibitors
  申请人：Neuroscienze Pharmaness S.C. A R.L.

  公开号：EP2223914A1

  公开（公告）日：2010-09-01

  Condensed tricyclic compounds having a condensed structure containing one phenyl and one pyrazole ring linked with each other by a central ring rcomprising from five to eight atoms, having affinity for the CB1 and/or CB2 receptors, with central nervous system and/or peripheral activity, of formula (I) : wherein the various substituents are as defined in the description. The compounds show affinity for the CB1 and/or CB2 cannabinoidergic receptors.

  具有紧凑结构的三环化合物，其中包含一个苯环和一个吡唑环，通过一个含有五至八个原子的中心环相互连接，具有对CB1和/或CB2受体的亲和力，具有中枢神经系统和/或外周活性，化学式为(I)：其中各种取代基如描述中定义。这些化合物显示对CB1和/或CB2大麻素受体的亲和力。
• Tricyclic pyrazole derivatives and microemulsions thereof as CB1- and/or CB2-inhibitors
  申请人：Neuroscienze Pharmaness S.C. A R.L.

  公开号：EP2223913A1

  公开（公告）日：2010-09-01

  Microemulsions of pharmaceutical compositions comprising the following components (% by weight), the sum of the components being 100%: S) from 0.01 to 95% of one or more compounds selected from surfactants, polymers forming organized structures as: aggregates, micelles, liquid crystals, vesicles, in the liquid in which they are solublized, O) from 0.01 to 95% of one or more oils selected from esters of C4-C32 acids or C4-C32 acids, PA) from 0.001 to 90% of compounds having affinity for the CB1 and/or CB2 cannabinoidergic receptors of formula A': AD) from 0 to 60% by weight of one or more compounds selected from modifiers of the water and/or oil polarity, modifiers of the film curvature of component S), co-surfactants, water or a saline aqueous solution the difference to 100%, wherein the ratio by weight S)/PA) is lower than that of microemulsions wherein component O) is absent.

  医药组合物的微乳液包含以下组分（按重量百分比计），各组分之和为100%：S）从0.01到95%的一种或多种从表面活性剂、形成有序结构的聚合物，如：聚集体、胶束、液晶、囊泡，在它们溶解的液体中选择的化合物，O）从0.01到95%的一种或多种选择自C4-C32酸酯或C4-C32酸的油，PA）从0.001到90%的具有亲和力的化合物CB1和/或CB2大麻素受体的配方A'，AD）从0到60%的一种或多种选择自水和/或油极性修饰剂，成分S）的膜曲率修饰剂，共表面活性剂，水或盐水溶液的差异为100%，其中按重量比S）/PA）低于不含成分O）的微乳液。
• PHARMACEUTICAL COMPOUNDS
  申请人：LAZZARI Paolo

  公开号：US20100215741A1

  公开（公告）日：2010-08-26

  Condensed tricyclic compounds having a condensed structure containing one phenyl and one pyrazole ring linked with each other by a central ring comprising from five to eight atoms, having affinity for the CB1 and/or CB2 receptors, with central nervous system and/or peripheral activity, of formula (I): wherein the various substituents are as defined in the description. The compounds show affinity for the CB1 and/or CB2 cannabinoidergic receptors.

  具有紧凑结构的三环化合物，包含一个苯环和一个吡唑环，通过一个由五至八个原子组成的中心环相互连接，在CB1和/或CB2受体上具有亲和力，具有中枢神经系统和/或外周活性，化学式（I）如下：其中各种取代基如描述中所定义。这些化合物对CB1和/或CB2类大麻素受体具有亲和力。
• Tricyclic Pyrazoles. 4. Synthesis and Biological Evaluation of Analogues of the Robust and Selective CB₂ Cannabinoid Ligand 1-(2‘,4‘-Dichlorophenyl)-6-methyl-<i>N</i>-piperidin-1-yl- 1,4-dihydroindeno[1,2-<i>c</i>]pyrazole-3-carboxamide
  作者：Gabriele Murineddu、Paolo Lazzari、Stefania Ruiu、Angela Sanna、Giovanni Loriga、Ilaria Manca、Matteo Falzoi、Christian Dessì、Maria M. Curzu、Giorgio Chelucci、Luca Pani、Gérard A. Pinna

  DOI：10.1021/jm060920d

  日期：2006.12.1

  New analogues (2a-p) of the previously reported CB2 ligands 6-methyl- and 6-chloro-1-(2',4'-dichlorophenyl)-N-piperidin-1-yl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamides (1a,b) have been synthesized and evaluated for cannabinoid receptor affinity. One example, 1-(2',4'-dichlorophenyl)-6-methyl-N-cyclohexyilamine-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide (2a) was shown to have single digit nanomolar affinity for cannabinoid CB2 receptors. Furthermore, compounds 2a and 2b, as well as lead structures 1a, b, were also shown to be agonist in an in vitro model based on human promyelocytic leukemia HL-60 cells.