[3-methyl-5,10-dihydropyrrolo[1,2-b]isoquinoline-1,2-diyl]dimethanol | 1147550-63-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: [3-methyl-5,10-dihydropyrrolo[1,2-b]isoquinoline-1,2-diyl]dimethanol
• 英文别名: (1-Hydroxymethyl-3-methyl-5,10-dihydro-pyrrolo[1,2-b]isoquinolin-2-yl)methanol；(2-Hydroxymethyl-3-methyl-5,10-dihydropyrrolo[1,2-b]isoquinolin-1-yl)methanol；[1-(hydroxymethyl)-3-methyl-5,10-dihydropyrrolo[1,2-b]isoquinolin-2-yl]methanol
• CAS: 1147550-63-7
• 化学式: C₁₅H₁₇NO₂
• 分子量: 243.305
• InChiKey: BVWJQOIYMKGOCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  45.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [3-methyl-5,10-dihydropyrrolo[1,2-b]isoquinoline-1,2-diyl]dimethanol 、 异氰酸甲酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以44.5%的产率得到[3-methyl-5,10-dihydropyrrolo[1,2-b]isoquinoline-1,2-diyl]bis(methylene) bis(methylcarbamate)
  参考文献：
  名称：

  SYNTHESIS OF 8H-3A-AZA-CYCLOPENTA[A]INDENES AND 5,10-DIHYDROPYRROLO[1,2-B]ISOQUINOLINES DERIVATIVES AND THEIR USE AS ANTITUMOR THERAPEUTIC AGENTS

  摘要：

  本公开涉及一系列8H-3a-氮杂环戊二烯-1-基和5,10-二氢吡咯并[1,2-b]异喹啉衍生物的双(羟甲基)和其双(氨基甲酸酯)（公式I-公式IV），作为DNA双烷基化剂。初步的抗肿瘤研究表明，本公开的化合物在体外可能表现出强大的细胞毒性，并在人类肿瘤移植物模型中表现出抗肿瘤治疗效果，并且可能几乎不会对紫杉醇或长春碱产生交叉耐药性。结果表明，本公开的化合物具有强大的抗肿瘤治疗效果，并有望在临床应用中发挥潜力。

  公开号：

  US20090117125A1
• 作为产物：
  描述：

  dimethyl 4,9-dihydro-1-methylpyrrolo<1,2-b>isoquinoline-2,3-dicarboxylate 在 lithium aluminium tetrahydride 、 sodium hydroxide 、 水 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 2.0h， 以76.2%的产率得到[3-methyl-5,10-dihydropyrrolo[1,2-b]isoquinoline-1,2-diyl]dimethanol
  参考文献：
  名称：

  SYNTHESIS OF 8H-3A-AZA-CYCLOPENTA[A]INDENES AND 5,10-DIHYDROPYRROLO[1,2-B]ISOQUINOLINES DERIVATIVES AND THEIR USE AS ANTITUMOR THERAPEUTIC AGENTS

  摘要：

  本公开涉及一系列8H-3a-氮杂环戊二烯-1-基和5,10-二氢吡咯并[1,2-b]异喹啉衍生物的双(羟甲基)和其双(氨基甲酸酯)（公式I-公式IV），作为DNA双烷基化剂。初步的抗肿瘤研究表明，本公开的化合物在体外可能表现出强大的细胞毒性，并在人类肿瘤移植物模型中表现出抗肿瘤治疗效果，并且可能几乎不会对紫杉醇或长春碱产生交叉耐药性。结果表明，本公开的化合物具有强大的抗肿瘤治疗效果，并有望在临床应用中发挥潜力。

  公开号：

  US20090117125A1

文献信息

• SYNTHESIS OF 4H-BENZO[D]PYRROLO[1,2-A]THIAZOLES AND INDOLIZINO[6,7-b]INDOLE DERIVATIVES AND THEIR USE AS ANTITUMOR THERAPEUTIC AGENTS
  申请人：Su Tsann-Long

  公开号：US20130178629A1

  公开（公告）日：2013-07-11

  The present invention provides a series of 2,3-bis(hydroxymethyl)-4H-benzo[d]pyrrolo-[1,2-a]thiazoles and 1,2-bis(hydroxymethyl)indolizino[6,7-b]indole derivatives and their bis(alkylcarbamates) derivatives. These derivatives were designed as bi-functional DNA cross-linking agents. The in vitro cytotoxicity study of these compounds revealed that they exhibit significant anti-proliferative activity in inhibiting human lymphoblastic leukemia and various solid tumor cell growth. The compounds also exhibit therapeutic efficacy against human breast carcinoma and lung cancer in xenograft model. The compounds generally possess potent antitumor activity to kill various human solid tumors and have high potential for clinical applications.

  本发明提供了一系列2,3-双(羟甲基)-4H-苯并[d]吡咯-[1,2-a]噻唑和1,2-双(羟甲基)吲哚并[6,7-b]吲哚衍生物及其双(烷基氨基甲酸酯)衍生物。这些衍生物被设计为具有双功能DNA交联作用的剂。对这些化合物进行的体外细胞毒性研究表明，它们在抑制人淋巴母细胞白血病和各种实体肿瘤细胞生长方面表现出显著的抗增殖活性。这些化合物还在异种移植模型中对人类乳腺癌和肺癌表现出治疗效果。这些化合物通常具有强大的抗肿瘤活性，可以杀死各种人类实体肿瘤，并具有高潜力用于临床应用。
• Synthesis of 8H-3A-aza-cyclopenta [A ]indenes and 5,10-dihydropyrrolo[1,2-B]isoquinolines derivatives and their use as antitumor therapeutic agents
  申请人：Su Tsann-Long

  公开号：US08410130B2

  公开（公告）日：2013-04-02

  The present disclosure relates to a series of bis(hydroxymethyl) and its bis(carbamate) of 8H-3a-azacyclopenta[a]indene-1-yl and 5,10-dihydropyrrolo-[1,2-b]isoquinolines derivatives (Formula I-Formula IV) as DNA di-alkylating agents. The preliminary antitumor studies indicated that compounds disclosed herein could exhibit potent cytotoxicity in vitro and antitumor therapeutic efficacy in human tumor xenografts and could have little or no cross-resistance to either Taxol or Vinblastine. The results demonstrated that compounds disclosed herein possess potent antitumor therapeutic efficacy and are expected to have potential for clinical applications.

  本公开涉及一系列8H-3a-氮杂环五环[1]吲哚-1-基和5,10-二氢吡咯并[1,2-b]异喹啉衍生物的双(羟甲基)和其双(氨基甲酸酯) (公式I-公式IV)，作为DNA二烷基化剂。初步的抗肿瘤研究表明，本公开的化合物在体外可能表现出强烈的细胞毒性和人类肿瘤异种移植物的抗肿瘤治疗效果，并且可能没有对紫杉醇或长春新碱的交叉耐药性。结果表明，本公开的化合物具有强大的抗肿瘤治疗效果，并有望在临床应用中发挥潜力。
• Novel bifunctional alkylating agents, 5,10-dihydropyrrolo[1,2-b]isoquinoline derivatives, synthesis and biological activity
  作者：Ravi Chaniyara、Naval Kapuriya、Huajin Dong、Pei-Chih Lee、Sharda Suman、Bhavin Marvania、Ting-Chao Chou、Te-Chang Lee、Rajesh Kakadiya、Anamik Shah、Tsann-Long Su

  DOI：10.1016/j.bmc.2010.11.030

  日期：2011.1

  A series of linear pyrrolo[1,2-b]isoquinoline derivatives was synthesized for antitumor evaluation. The preliminary antitumor studies reveal that both bis(hydroxymethyl) and their bis(alkylcarbamate) derivatives show significant antitumor activity in inhibiting various human tumor cell growth in vitro. 1,2-Bis(hydroxymethyl)-3-methyl-5,10-dihydropyrrolo[1,2-b] isoquinoline (20a) was selected for antitumor studies in animal models. The results show that this agent can induce complete tumor remission or significant suppression in nude mice bearing human breast (MX-1) xenograft and ovarian (SK-OV-3) xenografts, respectively. Alkaline agarose gel shifting assay showed that 20a is able to cross-link with DNA. Studies on the cell cycle inhibition revealed that this agent induces cell arrest at G2/M phase. The results warrant further antitumor investigation against other human tumor growth in animal models. (C) 2010 Elsevier Ltd. All rights reserved.
• US8410130B2
  申请人：——

  公开号：US8410130B2

  公开（公告）日：2013-04-02
• US8703951B2
  申请人：——

  公开号：US8703951B2

  公开（公告）日：2014-04-22