2-amino-9H-indeno[2,1-d]pyrimidin-4-yl 4-nitrobenzenesulfonate | 1126602-50-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-amino-9H-indeno[2,1-d]pyrimidin-4-yl 4-nitrobenzenesulfonate
• 英文别名: 4-nitro-benzenesulfonic acid 2-amino-9H-indeno[2,1-d]pyrimidin-4-ylester；(2-amino-9H-indeno[2,1-d]pyrimidin-4-yl) 4-nitrobenzenesulfonate
• CAS: 1126602-50-3
• 化学式: C₁₇H₁₂N₄O₅S
• 分子量: 384.372
• InChiKey: JLTSZDWNRKQXOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  149
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-amino-9H-indeno[2,1-d]pyrimidin-4-yl 4-nitrobenzenesulfonate 、 4-氯-2-氟苯胺 以 1,4-二氧六环 为溶剂， 以18%的产率得到N4-(4-chloro-2-fluorophenyl)-9H-indeno[2,1-d]pyrimidine-2,4-diamine
  参考文献：
  名称：

  Novel tricyclic indeno[2,1-d]pyrimidines with dual antiangiogenic and cytotoxic activities as potent antitumor agents

  摘要：

  We designed, synthesized and evaluated 13 novel tricyclic indeno[2,1-d]pyrimidines as RTK inhibitors. These analogues were synthesized via a Dieckmann condensation of 1,2-phenylenediacetonitrile followed by cyclocondensation with guanidine carbonate to afford the 2-amino-3,9-dihydro-indeno[2,1-d]pyrimidin-4-one. Sulfonation of the 4-position followed by displacement with appropriately substituted anilines afforded the target compounds. These compounds were potent inhibitors of platelet-derived growth factor receptor beta (PDGFR beta) and inhibited angiogenesis in the chicken embryo chorioallantonic membrane (CAM) assay compared to standards. In addition, compound 7 had a two digit nanomolar GI(50) against nine tumor cell lines, a submicromolar GI(50) against 29 of other tumor cell lines in the preclinical NCI 60 tumor cell line panel. Compound 7 also demonstrated significant in vivo inhibition of tumor growth and angiogenesis in a B16-F10 syngeneic mouse melanoma model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.068
• 作为产物：
  描述：

  1,2-苯二乙腈 在 4-二甲氨基吡啶 、 硫酸 、 potassium tert-butylate 、 sodium 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 、 叔丁醇 为溶剂， 反应 18.0h， 生成 2-amino-9H-indeno[2,1-d]pyrimidin-4-yl 4-nitrobenzenesulfonate
  参考文献：
  名称：

  Novel tricyclic indeno[2,1-d]pyrimidines with dual antiangiogenic and cytotoxic activities as potent antitumor agents

  摘要：

  We designed, synthesized and evaluated 13 novel tricyclic indeno[2,1-d]pyrimidines as RTK inhibitors. These analogues were synthesized via a Dieckmann condensation of 1,2-phenylenediacetonitrile followed by cyclocondensation with guanidine carbonate to afford the 2-amino-3,9-dihydro-indeno[2,1-d]pyrimidin-4-one. Sulfonation of the 4-position followed by displacement with appropriately substituted anilines afforded the target compounds. These compounds were potent inhibitors of platelet-derived growth factor receptor beta (PDGFR beta) and inhibited angiogenesis in the chicken embryo chorioallantonic membrane (CAM) assay compared to standards. In addition, compound 7 had a two digit nanomolar GI(50) against nine tumor cell lines, a submicromolar GI(50) against 29 of other tumor cell lines in the preclinical NCI 60 tumor cell line panel. Compound 7 also demonstrated significant in vivo inhibition of tumor growth and angiogenesis in a B16-F10 syngeneic mouse melanoma model. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.068

文献信息

• TRICYCLIC COMPOUNDS HAVING CYTOSTATIC AND/OR CYTOTOXIC ACTIVITY AND METHODS OF USE THEREOF
  申请人：Gangjee Aleem

  公开号：US20090062318A1

  公开（公告）日：2009-03-05

  The present invention provides tricyclic compounds having cytostatic and cytotoxic activity in a single molecule having receptor tyrosine kinase(s), dihydrofolate reductase, thymidylate synthase and/or dihydroorotate dehydrogenase inhibitory activity, which are useful as anti-angiogenic and anti-tumor agents. Also provided are methods of utilizing these inhibitors to treat tumor cells and other proliferative diseases and disorders.

  本发明提供了一种三环化合物，其在单个分子中具有受体酪氨酸激酶、二氢叶酸还原酶、胸苷酸合成酶和/或二氢甲氧呋喃脱氢酶的抑制活性，这些化合物具有细胞静止和细胞毒活性，可用作抗血管生成和抗肿瘤药物。还提供了利用这些抑制剂治疗肿瘤细胞和其他增殖性疾病和紊乱的方法。
• Tricyclic Compounds Having Cytostatic and/or Cytoxic Activity and Methods of Use Thereof
  申请人：Gangjee Aleem

  公开号：US20110207757A1

  公开（公告）日：2011-08-25

  The present invention provides tricyclic compounds having cytostatic and cytotoxic activity in a single molecule having receptor tyrosine kinase(s), dihydrofolate reductase, thymidylate synthase and/or dihydroorotate dehydrogenase inhibitory activity, which are useful as anti-angiogenic and anti-tumor agents. Also provided are methods of utilizing these inhibitors to treat tumor cells and other proliferative diseases and disorders.

  本发明提供了三环化合物，其在单一分子中具有受体酪氨酸激酶、二氢叶酸还原酶、胸腺嘧啶合成酶和/或二氢乳酸脱氢酶抑制活性，具有细胞增殖抑制和细胞毒性活性，可用作抗血管生成和抗肿瘤剂。还提供了利用这些抑制剂治疗肿瘤细胞和其他增殖性疾病和疾病的方法。
• Tricyclic Compounds Having Cytostatic and/or Cytotoxic Activity and Methods of Use Thereof
  申请人：Duquesne University of the Holy Ghost

  公开号：US20150141445A1

  公开（公告）日：2015-05-21

  The present invention provides tricyclic compounds having cytostatic and cytotoxic activity in a single molecule having receptor tyrosine kinase(s), dihydrofolate reductase, thymidylate synthase and/or dihydroorotate dehydrogenase inhibitory activity, which are useful as anti-angiogenic and anti-tumor agents. Also provided are methods of utilizing these inhibitors to treat tumor cells and other proliferative diseases and disorders.

  本发明提供了三环化合物，其在单个分子中具有受体酪氨酸激酶、二氢叶酸还原酶、胸腺嘧啶合成酶和/或二氢乳酸脱氢酶抑制活性，具有细胞增殖抑制和细胞毒性活性，可用作抗血管生成和抗肿瘤剂。还提供了利用这些抑制剂治疗肿瘤细胞和其他增殖性疾病和疾病的方法。
• US7960400B2
  申请人：——

  公开号：US7960400B2

  公开（公告）日：2011-06-14
• US8314114B2
  申请人：——

  公开号：US8314114B2

  公开（公告）日：2012-11-20