[3-(4-fluorophenyl)-5,10-dihydropyrrolo[1,2-b]isoquinoline-1,2-diyl]dimethanol | 1147551-29-8

• 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-(4-fluorophenyl)-5,10-dihydropyrrolo[1,2-b]isoquinoline-1,2-diyl]dimethanol
• 英文别名: [3-(4-flourophenyl)-1-hydroxymethyl-5,10-dihydro-pyrrolo[1,2-b]isoquinolin-2-yl]-methanol；[3-(4-fluorophenyl)-1-hydroxymethyl-5,10-dihydro-pyrrolo[1,2-b]isoquinolin-2-yl]-methanol；[3-(4-Fluorophenyl)-2-(hydroxymethyl)-5,10-dihydropyrrolo[1,2-b]isoquinolin-1-yl]methanol
• CAS: 1147551-29-8
• 化学式: C₂₀H₁₈FNO₂
• 分子量: 323.367
• InChiKey: AZPVOZPYNPBHHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  45.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [3-(4-fluorophenyl)-5,10-dihydropyrrolo[1,2-b]isoquinoline-1,2-diyl]dimethanol 、 异氰酸异丙酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以81%的产率得到[3-(4-fluorophenyl)-5,10-dihydropyrrolo[1,2-b]isoquinoline-1,2-diyl]bis(methylene) bis(iso-propylcarbamate)
  参考文献：
  名称：

  Novel bifunctional alkylating agents, 5,10-dihydropyrrolo[1,2-b]isoquinoline derivatives, synthesis and biological activity

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2010.11.030
• 作为产物：
  描述：

  3-(4-fluorophenyl)-5,10-dihydropyrrolo[1,2-b]isoquinoline-1,2-dicarboxylic acid dimethyl ester 在 lithium aluminium tetrahydride 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 以74%的产率得到[3-(4-fluorophenyl)-5,10-dihydropyrrolo[1,2-b]isoquinoline-1,2-diyl]dimethanol
  参考文献：
  名称：

  Novel bifunctional alkylating agents, 5,10-dihydropyrrolo[1,2-b]isoquinoline derivatives, synthesis and biological activity

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2010.11.030

文献信息

• 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：US20090117125A1

  公开（公告）日：2009-05-07

  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。
• US8410130B2
  申请人：——

  公开号：US8410130B2

  公开（公告）日：2013-04-02
• 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.