2,3-dihydropyrrolo<1,2,3-de><1,4>benzothiazin-6-carboxylic acid ethyl ester | 152712-41-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2,3-dihydropyrrolo<1,2,3-de><1,4>benzothiazin-6-carboxylic acid ethyl ester
• 英文别名: ethyl 2,3-dihydro-[1,4]thiazino[2,3,4-hi]indole-6-carboxylate；Ethyl 9-thia-1-azatricyclo[6.3.1.04,12]dodeca-2,4(12),5,7-tetraene-3-carboxylate
• CAS: 152712-41-9
• 化学式: C₁₃H₁₃NO₂S
• 分子量: 247.318
• InChiKey: JAGISMKBBPHLDS-UHFFFAOYSA-N

物化性质

• 沸点：
  433.0±33.0 °C(predicted)
• 密度：
  1.33±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  56.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,3-dihydropyrrolo<1,2,3-de><1,4>benzothiazin-6-carboxylic acid ethyl ester 在 aluminum (III) chloride 、 copper chromite 、 水 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 sodium hydroxide 作用下， 以 N-甲基吡咯烷酮 、 喹啉 、 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 38.0h， 生成 (S)-tert-butyl 3-((4-(1,1-dioxido-2,3-dihydro-[1,4]thiazino[2,3,4-hi]indol-6-yl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)piperidine-1-carboxylate
  参考文献：
  名称：

  [EN] INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7)
  [FR] INHIBITEURS DE LA KINASE 7 DÉPENDANTE DES CYCLINES (CDK7)

  摘要：

  公开号：

  WO2018013867A8
• 作为产物：
  描述：

  3,4-二氢-2H-1,4-苯并噻嗪 在 magnesium chloride 作用下， 以 四氢呋喃 、 乙二醇甲醚 为溶剂， 反应 31.0h， 生成 2,3-dihydropyrrolo<1,2,3-de><1,4>benzothiazin-6-carboxylic acid ethyl ester
  参考文献：
  名称：

  [EN] INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7)
  [FR] INHIBITEURS DE LA KINASE 7 DÉPENDANTE DES CYCLINES (CDK7)

  摘要：

  公开号：

  WO2018013867A8

文献信息

• Development of high-affinity 5-HT3 receptor antagonists. Structure-affinity relationships of novel 1,7-annulated indole derivatives. 1
  作者：Ineke van Wijngaarden、Derk Hamminga、Rolf van Hes、Piet J. Standaar、Jacobus Tipker、Martin T. M. Tulp、Frans Mol、Berend Olivier、Adriaan de Jonge

  DOI：10.1021/jm00075a026

  日期：1993.11

  On the basis of the structures of ondansetron and GR 65,630, its ring-opened C-linked methylimidazole analogue, novel 1,7-annelated indole derivatives were synthesized as potential 5-HT3 antagonists. Receptor binding studies show that all compounds display a high affinity for the 5-HT3 receptors. In both series annelation results in compounds being 7 and 4 times more potent than the references ondansetron and GR 65,630, respectively. Similar to ondansetron, the 1,7-annelated indoles show little stereoselectivity. The (-)-isomers are only slightly more potent than the (+)-isomers. The receptor binding profile of l-10-[(2-methyl-1H-imidazol-1-yl)methyl]-5,6,8,9,10,11-hexahydro-4H-pyrido[3,2,1-jk]carbazol-11-one hydrochloride (24b) (INN cilansetron) shows that the compound displays, besides a high affinity for 5-HT3 receptors (K(i) = 0. 19 nM), a weak affinity for sigma-receptors (K(i) = 340 nM), muscarine M1 receptors (K(i) = 910 nM), and 5-HT4 receptors (K(i_ = 960 nM) and no affinity (K(i) greater-than-or-equal-to 5000 nM) for all the other receptor types tested (n = 37). The new compounds fit the proposed necessary chemical template for binding: a heteroaromatic ring system, a coplanar carbonyl group, and a nitrogen center at well-defined distances. The enhanced potency of the annelated 1,7-indole derivatives indicates that the extra ring provides a favorable hydrophobic area for interaction with the 5-HT3 receptor site. In vivo cilansetron is more potent and induces less central side effects than ondansetron. At present cilansetron is in clinical trials.
• [EN] INHIBITORS OF CYCLIN DEPENDNT KINASE 7 (CDK7)<br/>[FR] INHIBITEURS DE LA KINASE 7 DÉPENDANTE DES CYCLINES (CDK7)
  申请人：MARINEAU JASON J

  公开号：WO2018013867A1

  公开（公告）日：2018-01-18

  The present invention provides novel compounds of Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.