chimmitecan | 185425-25-6

• 物质功能分类: 原料药 - 抑制剂
• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: chimmitecan
• 英文别名: 9-allyl-10-hydroxycamptothecin；(19S)-19-ethyl-7,19-dihydroxy-8-prop-2-enyl-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione
• CAS: 185425-25-6
• 化学式: C₂₃H₂₀N₂O₅
• 分子量: 404.422
• InChiKey: AXXPNDLHTNUMIK-QHCPKHFHSA-N

物化性质

• 沸点：
  803.0±65.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  6

制备方法与用途

抑制剂

吉米替康是一种Topoisomerase I抑制剂，展现出有效的体内和体外活性。

靶点

Topoisomerase

反应信息

• 作为反应物：
  描述：

  chimmitecan 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 溶剂黄146 为溶剂， 生成 (5S)-18-(bromomethyl)-5-ethyl-5-hydroxy-7,19-dioxa-11,24-diazahexacyclo[11.11.0.02,11.04,9.015,23.016,20]tetracosa-1(24),2,4(9),13,15(23),16(20),21-heptaene-6,10-dione
  参考文献：
  名称：

  Synthesis and antitumor activity of the hexacyclic camptothecin derivatives

  摘要：

  A series of hexacyclic camptothecin derivatives were synthesized to test for antitumor activity as topoisomerase I inhibitor. The strategy of synthesis was used for the formation of additional furan and dihydrofuran rings fused with 9- and 10-positions of camptothecin. All of the hexacyclic camptothecins were assayed for cytotoxicity against four human tumor cell lines, HL60, BEL-7402, HCT-116, and HeLa, and showed very impressive cytotoxicity activity in vitro. Enzyme activity of the hexacyclic camptothecins was evaluated, being equal or superior to that of SN-38. The stability of four compounds was assessed in human plasma. Two of these compounds were chosen to test for antitumor activity in vivo against Sarcoma-180. The results suggested that additional furan and dihydrofuran rings could improve the antitumor activity in vitro and vivo, though the stability of the lactone ring did not increase. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.04.063
• 作为产物：
  描述：

  10-羟基喜树碱 在 吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 N-溴代丁二酰亚胺(NBS) 、 cesium fluoride 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 chimmitecan
  参考文献：
  名称：

  Synthesis of 9-Allyl-10-hydroxycamptothecin via Suzuki Reaction

  摘要：

  A facile and eco‐friendly approach for synthesizing 9‐allyl‐10‐hydroxycamptothecin (2), a key intermediate for the preparation of camptothecin analogs, is described. The product was obtained in good yield and high purity (≥99% HPLC) under mild Suzuki reaction condition.

  DOI：

  10.1002/jhet.1549

文献信息

• SYNTHESIS METHOD OF 9-ALLYLCAMPTOTHECIN DERIVATIVES
  申请人：SHANGHAI HAIHE PHARMACEUTICAL CO., LTD.

  公开号：US20160340364A1

  公开（公告）日：2016-11-24

  A method for preparing 9-allylcamptothecin derivatives using compound 14 as an essential intermediate. The total yield of the method is high.

  使用14号化合物作为必要中间体制备9-烯丙基喜树碱衍生物的方法。该方法的总产率很高。
• Synthesis and Biological Evaluation of 10‐Substituted Camptothecin Derivatives with Improved Water Solubility and Activity
  作者：Xue‐Yan Yang、Hong‐Yi Zhao、Hao Lei、Bo Yuan、Shuai Mao、Minghang Xin、San‐Qi Zhang

  DOI：10.1002/cmdc.202000753

  日期：2021.3.18

  Despite remarkable clinical achievements, camptothecin (CPT) still suffers from poor solubility and severe toxicity. Therefore, it is necessary to redevelop CPT derivatives as supplementary antitumor agents with good water solubility and small side effects. In this work, 27 camptothecin derivatives were synthesized and screened for their cytotoxicity against A549 (lung) and HCT‐116 (colon) cancer cell

  尽管临床上取得了显着的成就，但喜树碱（CPT）仍然存在溶解性差和毒性严重的问题。因此，有必要重新开发CPT衍生物作为水溶性好、副作用小的辅助抗肿瘤剂。在这项工作中，合成了 27 种喜树碱衍生物并筛选了它们对 A549（肺）和 HCT-116（结肠）癌细胞系的细胞毒性。其中，化合物B7，7-乙基-10-（2-氧代-2-（4-甲基哌啶-1-基）乙氧基）喜树碱，在体外被证明是比 SN-38 更有效的抗肿瘤剂。它们对细胞增殖和集落形成的抑制活性和对细胞周期和细胞凋亡过程的干扰作用。此外，分子对接模型显示B7可以与拓扑异构酶 I-DNA 复合物相互作用，B7在水中的溶解度达到 5.73 μg/mL。此外，B7在 0.4 和 2.0 mg/kg 的剂量下显着抑制 A549 异种移植模型中的肿瘤生长，并且显示出与伊立替康相当的最小致死剂量。这些结果表明，B7具有改善的溶解性、增强的活性和可接受的急性毒性，可用作开发新型抗癌剂的先导化合物。
• CAMPTOTHECIN DERIVATIVES HAVING ANTI-TUMOR ACTIVITY
  申请人：Lei Xiaoguang

  公开号：US20140011833A1

  公开（公告）日：2014-01-09

  Disclosed are novel camptothecin derivatives having anti-tumor activity (the basic structure thereof is as shown in the figure) and compositions of such compounds and use thereof. The compounds according to the present invention exhibit very good water solubility and stability, show good selectivity among drugs of the same category, and have a very high therapeutic index. Such compounds are promising as therapeutic agents for treating tumors.

  本发明公开了具有抗肿瘤活性的新型喜树碱衍生物（其基本结构如图所示），以及这些化合物的组合物和使用方法。本发明的化合物具有非常好的水溶性和稳定性，显示出在同一类别药物中良好的选择性，并具有非常高的治疗指数。这些化合物作为治疗肿瘤的治疗剂具有很大的潜力。
• Water soluble camptothecin analogs
  申请人：SmithKline Beecham Corporation

  公开号：US06046209A1

  公开（公告）日：2000-04-04

  The present invention provides water soluble camptothecin analogs of Formula I: ##STR1## which are particularly useful as antineoplastic agents; pharmaceutical compositions thereof; and a method of treating cancer in an animal in need thereof, including human beings, comprising inhibition of the growth of tumor cells in said animal by administration of an effective amount of a compound of Formula I.

  本发明提供了一种水溶性的喜树碱类似物，化学式为I：##STR1## 特别适用于作为抗肿瘤剂；其中的药物组成；以及一种治疗需要治疗癌症的动物，包括人类的方法，通过给动物注射化合物I的有效量，抑制该动物体内肿瘤细胞的生长。
• HDAC INHIBITING DERIVATIVES OF CAMPTOTHECIN
  申请人：Chen Yi

  公开号：US20130281402A1

  公开（公告）日：2013-10-24

  The disclosure includes hydroxamic compounds of Formula I: (Formula I) wherein Z, L, R 1 , R 2 , and R 3 are defined herein. Also disclosed is a method for treating a neoplastic disease or an immune disease with these compounds.

  本公开涉及式I的羟肟酰胺化合物：（式I），其中Z，L，R1，R2和R3的定义如本文所述。还公开了使用这些化合物治疗肿瘤性疾病或免疫性疾病的方法。