3,10-二氢吡咯并[3,2-a]咔唑 | 101179-99-1

• 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
• 中文名称: 3,10-二氢吡咯并[3,2-a]咔唑
• 英文名称: 3,10-dihydro-pyrrolo[3,2-a]carbazole
• 英文别名: 3,10-dihydropyrrolo[3,2-a]carbazole
• CAS: 101179-99-1
• 化学式: C₁₄H₁₀N₂
• 分子量: 206.247
• InChiKey: KKENGBBYKXPQFM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  31.6
• 氢给体数：
  2
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  3,10-二氢吡咯并[3,2-a]咔唑 、 N,N-二甲基甲酰胺 在 草酰氯 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.33h， 以66%的产率得到3,10-dihydropyrrolo[3,2-a]carbazole-1-carbaldehyde
  参考文献：
  名称：

  Synthesis, Kinase Inhibitory Potencies, and in Vitro Antiproliferative Evaluation of New Pim Kinase Inhibitors

  摘要：

  Members of the Pim kinase family have been identified as promising targets for the development of antitumor agents. After a screening of pyrrolo[2,3-a]- and [3,2-a]carbazole derivatives toward 66 protein kinases, we identified pyrrolo[2,3-a]carbazole as a new scaffold to design potent Pim kinase inhibitors. In particular, compound 9 was identified as a low nM selective Pim inhibitor. Additionally, several pyrrolo[2,3-a]carbazole derivatives showed selectivity for Pim-1 and Pim-3 over Pim-2. In vitro antiproliferative activities of 9 and 28, the most potent Pim inhibitors identified, were evaluated toward three human solid cancer cell lines (PA1, PC3, and DU145) and one human fibroblast primary culture, revealing IC50 values in the micromolar range. Finally, the crystal structure of Pim-1 complexed with lead compound 9 was determined. The structure revealed a non-ATP mimetic binding mode with no hydrogen bonds formed with the kinase hinge region and explained the selectivity of pyrrolo[2,3-a]carbazole derivatives for Pim kinases.

  DOI：

  10.1021/jm901018f
• 作为产物：
  描述：

  3-benzenesulfonyl-3,10-dihydropyrrolo[3,2-a]carbazole 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 15.0h， 以96%的产率得到3,10-二氢吡咯并[3,2-a]咔唑
  参考文献：
  名称：

  Synthesis, Kinase Inhibitory Potencies, and in Vitro Antiproliferative Evaluation of New Pim Kinase Inhibitors

  摘要：

  Members of the Pim kinase family have been identified as promising targets for the development of antitumor agents. After a screening of pyrrolo[2,3-a]- and [3,2-a]carbazole derivatives toward 66 protein kinases, we identified pyrrolo[2,3-a]carbazole as a new scaffold to design potent Pim kinase inhibitors. In particular, compound 9 was identified as a low nM selective Pim inhibitor. Additionally, several pyrrolo[2,3-a]carbazole derivatives showed selectivity for Pim-1 and Pim-3 over Pim-2. In vitro antiproliferative activities of 9 and 28, the most potent Pim inhibitors identified, were evaluated toward three human solid cancer cell lines (PA1, PC3, and DU145) and one human fibroblast primary culture, revealing IC50 values in the micromolar range. Finally, the crystal structure of Pim-1 complexed with lead compound 9 was determined. The structure revealed a non-ATP mimetic binding mode with no hydrogen bonds formed with the kinase hinge region and explained the selectivity of pyrrolo[2,3-a]carbazole derivatives for Pim kinases.

  DOI：

  10.1021/jm901018f

文献信息

• First Suzuki–Miyaura type cross-coupling of ortho-azidobromobenzene with arylboronic acids and its application to the synthesis of fused aromatic indole-heterocycles
  作者：Marc Pudlo、Dorottya Csányi、Fabien Moreau、György Hajós、Zsuzsanna Riedl、Janos Sapi

  DOI：10.1016/j.tet.2007.07.068

  日期：2007.10

  short synthesis of some fused indole-heterocycles has been achieved via Pd-catalyzed cross-coupling reactions between azido-2-bromobenzene and arylboronic acids and subsequent thermally induced nitrene insertion. Additionally, 4-amino-α-carboline, a versatile intermediate toward grossularine analogs has also been prepared by Suzuki–Miyaura cross-coupling of 4-pivaloylaminopyridine-3-boronic acid with

  通过叠氮基-2-溴苯与芳基硼酸之间的钯催化的交叉偶联反应以及随后的热诱导的腈插入，已经实现了一些稠合的吲哚杂环的短合成。此外，还通过Suzuki-Miyaura将4-新戊酰氨基吡啶3-硼酸与2-溴苯胺交叉偶联，然后进行简单的官能团转化，制备了一种通用的通向小卵磷脂类似物的中间体4-氨基-α-咔啉。
• Preventives and remedies for central nervous system diseases
  申请人：——

  公开号：US20030207863A1

  公开（公告）日：2003-11-06

  A prophylactic or therapeutic agent for central nervous system diseases based on amyloid &bgr;40 secretion inhibitory activity of a compound having urotensin II receptor antagonistic activity or a salt thereof.

  一种预防或治疗中枢神经系统疾病的药剂，基于一种具有尿泰松II受体拮抗活性或其盐的化合物对淀粉样蛋白β40分泌抑制活性。
• Agents and crystals for improving excretory potency of urinary bladder
  申请人：——

  公开号：US20020177593A1

  公开（公告）日：2002-11-28

  Agents for improving potentcy of the urinary bladder which comprises an amine compound of non-carbamate-type having an acetylcholinesterase-inhibiting action. Particularly, crystals of a tricyclic, condensed, heterocyclic derivative are provided, which possess an excellent action to inhibit acetylcholine esterase and an action to improve the excretory potency of urinary bladder. As an example, crystals of of 8-[3-[1-[(3-fluorophenyl)-methyl]-4-piperidinyl]-1-oxopropyl]-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one or a salt thereof and pharmaceutical compositions containing them are disclosed.

  改善膀胱功能的药剂，包括一种非卡巴酯类胺化合物，具有乙酰胆碱酯酶抑制作用。特别地，提供了一种三环、紧凑、杂环衍生物的晶体，具有优异的抑制乙酰胆碱酯酶作用和改善膀胱排泄功能的作用。例如，揭示了8-[3-[1-[(3-氟苯基)-甲基]-4-哌啶基]-1-氧代丙基]-1,2,5,6-四氢-4H-吡咯烷[3,2,1-ij]-喹啉-4-酮或其盐和含有它们的药物组合物。
• Agents for improving excretory potency of urinary bladder
  申请人：——

  公开号：US20040116457A1

  公开（公告）日：2004-06-17

  Agents for improving excretory potency of the urinary bladder which comprises an amine compound of non-carbamate-type having an acetylcholinesterase-inhibiting action.

  改善排泄能力的尿道代理，包括一种非卡巴酯型胺类化合物，具有乙酰胆碱酯酶抑制作用。
• Preventives/remedies for urinary disturbance
  申请人：Ishihara Yuji

  公开号：US20050197362A1

  公开（公告）日：2005-09-08

  Preventives/remedies for voiding disturbance containing a compound having both of an acetylcholinesterase inhibitory action and an α1 antagonistic action which exhibits an excellent effect of improving the urinary function of the bladder (i.e., effects of improving urine flow rate and voiding efficiency) without affecting the urinary pressure or the blood pressure.

  具有乙酰胆碱酯酶抑制作用和α1拮抗作用的化合物的预防/治疗措施，可以显著改善膀胱的尿液功能（即改善尿流率和排尿效率的效果），而不影响尿压或血压。