tert-butyl 5-(benzyloxy)-1-methyl-1,2-dihydro-3H-benzo[e]indole-3-carboxylate | 550356-45-1

• 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
• 英文名称: tert-butyl 5-(benzyloxy)-1-methyl-1,2-dihydro-3H-benzo[e]indole-3-carboxylate
• 英文别名: Tert-butyl 1-methyl-5-phenylmethoxy-1,2-dihydrobenzo[e]indole-3-carboxylate
• CAS: 550356-45-1
• 化学式: C₂₅H₂₇NO₃
• 分子量: 389.494
• InChiKey: PDVRCLSOHGXYGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 5-(benzyloxy)-1-methyl-1,2-dihydro-3H-benzo[e]indole-3-carboxylate 在 palladium on activated charcoal 盐酸 、 碳酸氢铵 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 5.5h， 生成 1-Methyl-2,3-dihydro-1H-benzo[e]indol-5-ol; hydrochloride
  参考文献：
  名称：

  Unsymmetrical DNA Cross-Linking Agents:  Combination of the CBI and PBD Pharmacophores

  摘要：

  A set of 10 compounds, each combining the seco-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (seco-CBI) and pyrrolo[2,1-c][1,4]benzodiazepine (PBD) pharmacophores, was designed and prepared. These compounds were anticipated to cross-link between N3 of adenine and N2 of guanine in the minor groove of DNA. The compounds, which differ in the chain length separating the two alkylation subunits, and the configuration of the CBI portion, showed great variation in cellular toxicity (over 4 orders of magnitude in a cell line panel) with the most potent example exhibiting IC50S in the pM range. Cytotoxicity correlated with the ability of the compounds to cross-link naked DNA. Cross-linking was also observed in living cells, at much lower concentrations than for a related symmetrical PBD dimer. A thermal cleavage assay was used to assess sequence selectivity, demonstrating that the CBI portion controlled the alkylation sites, while the PBD substituent increased the overall efficiency of alkylation. Several compounds were tested for in vivo activity using a tumor growth delay assay against WiDr human colon carcinoma xenografts, with one compound (the most cytotoxic and most efficient cross-linker) showing a statistically significant increase in survival time following a single iv dose.

  DOI：

  10.1021/jm020526p
• 作为产物：
  描述：

  (4-苄氧基-1-溴萘-2-基)氨基甲酸叔丁酯 在 偶氮二异丁腈 、 三正丁基氢锡 、 sodium hydride 作用下， 以 苯 为溶剂， 反应 1.0h， 生成 tert-butyl 5-(benzyloxy)-1-methyl-1,2-dihydro-3H-benzo[e]indole-3-carboxylate
  参考文献：
  名称：

  Unsymmetrical DNA Cross-Linking Agents:  Combination of the CBI and PBD Pharmacophores

  摘要：

  A set of 10 compounds, each combining the seco-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (seco-CBI) and pyrrolo[2,1-c][1,4]benzodiazepine (PBD) pharmacophores, was designed and prepared. These compounds were anticipated to cross-link between N3 of adenine and N2 of guanine in the minor groove of DNA. The compounds, which differ in the chain length separating the two alkylation subunits, and the configuration of the CBI portion, showed great variation in cellular toxicity (over 4 orders of magnitude in a cell line panel) with the most potent example exhibiting IC50S in the pM range. Cytotoxicity correlated with the ability of the compounds to cross-link naked DNA. Cross-linking was also observed in living cells, at much lower concentrations than for a related symmetrical PBD dimer. A thermal cleavage assay was used to assess sequence selectivity, demonstrating that the CBI portion controlled the alkylation sites, while the PBD substituent increased the overall efficiency of alkylation. Several compounds were tested for in vivo activity using a tumor growth delay assay against WiDr human colon carcinoma xenografts, with one compound (the most cytotoxic and most efficient cross-linker) showing a statistically significant increase in survival time following a single iv dose.

  DOI：

  10.1021/jm020526p

文献信息

• [EN] NEW TRICYCLIC 5-HT2 ANTAGONISTS<br/>[FR] NOUVEAUX ANTAGONISTES DE 5-HT2TRICYCLIQUES
  申请人：ANAMAR AB

  公开号：WO2020254322A1

  公开（公告）日：2020-12-24

  The present invention relates to tricyclic 1-amidino-4-methyl-[2,3 fused]-2-pyrroline derivatives of the general formula (I). The invention specifically relates to such derivatives which exhibit antagonizing activity towards serotonin 5-HT2B receptors. The present invention also relates to use of said compounds as a medicament and for the treatment of fibrosis, cardiovascular diseases, pain, IBD, inflammatory diseases, and cancer, as well as pharmaceutical compositions comprising one or more of said compounds and methods of treatment.

  本发明涉及一般式(I)的三环1-酰胺基-4-甲基-[2,3融合]-2-吡咯烯衍生物。该发明具体涉及表现出对5-羟色胺5-HT2B受体的拮抗活性的这些衍生物。本发明还涉及所述化合物作为药物的用途，用于治疗纤维化、心血管疾病、疼痛、炎症性肠病、炎症性疾病和癌症，以及包含一种或多种所述化合物的药物组合物和治疗方法。