14-amino-camptothecin | 1258494-59-5

• 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: 14-amino-camptothecin
• 英文别名: 14-Aminocamptothecin；(19S)-21-amino-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione
• CAS: 1258494-59-5
• 化学式: C₂₀H₁₇N₃O₄
• 分子量: 363.373
• InChiKey: QIDVDDJMONJMDF-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  27
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  14-amino-camptothecin 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 1.17h， 以32%的产率得到(6S)-6-ethyl-6-hydroxy-8-(hydroxymethyl)-4,10,20-triazapentacyclo[10.8.0.02,10.03,7.014,19]icosa-1(20),2,7,12,14,16,18-heptaene-5,9-dione
  参考文献：
  名称：

  14-Aminocamptothecins: Their Synthesis, Preclinical Activity, and Potential Use for Cancer Treatment

  摘要：

  14-Aminocamptothecins were synthesized in good yields by treating camptothecin (1a) and 7-ethylcamptothecin (1b) with 90% fuming nitric acid either neat or in acetic anhydride and then followed by I reduction of the resulting 14-nitrocamptothecins (2). 14-Aminocamptothecin (3a) and 7-ethyl-14-aminocamptothecin (313) demonstrated excellent cytotoxic potency against human tumor cell lines in vitro, and they are not substrates for any of the major clinically relevant efflux pumps (MDR1, MRP1, and BCRP). 3a and 3b showed similar cytotoxicity against human and mouse bone marrow progenitor cells. This is in contrast to many camptothecin analogues, which are substrates for efflux pumps and are dramatically more toxic to human marrow cells relative to murine. 3a and 3b demonstrated significant brain penetration when dosed orally in mice. 3b showed significantly better efficacy relative to topotecan when dosed orally in the three ectopic xenograft models, H460, HT29, and PC-3. On the basis of its favorable in vitro and in vivo profile, 3b warrants future development.

  DOI：

  10.1021/jm101354u
• 作为产物：
  描述：

  14-nitro-camptothecin 在 palladium 10% on activated carbon 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 14-amino-camptothecin
  参考文献：
  名称：

  [EN] CAMPTOTHECIN DERIVATIVES
  [FR] DÉRIVÉS DE CAMPTOTHÉCINE

  摘要：

  公开号：

  WO2010148138A3

文献信息

• [EN] CAMPTOTHECIN DERIVATIVES<br/>[FR] DÉRIVÉS DE CAMPTOTHÉCINE
  申请人：THRESHOLD PHARMACEUTICALS INC

  公开号：WO2010148138A3

  公开（公告）日：2011-05-12
• CAMPTOTHECIN DERIVATIVES
  申请人：Threshold Pharmaceuticals, Inc.

  公开号：EP2443125A2

  公开（公告）日：2012-04-25
• US8575188B2
  申请人：——

  公开号：US8575188B2

  公开（公告）日：2013-11-05
• 14-Aminocamptothecins: Their Synthesis, Preclinical Activity, and Potential Use for Cancer Treatment
  作者：Jian-Xin Duan、Xiaohong Cai、Fanying Meng、Jessica D. Sun、Qian Liu、Donald Jung、Hailong Jiao、Jackson Matteucci、Brian Jung、Deepthi Bhupathi、Dharmendra Ahluwalia、Heli Huang、Charles P. Hart、Mark Matteucci

  DOI：10.1021/jm101354u

  日期：2011.3.24

  14-Aminocamptothecins were synthesized in good yields by treating camptothecin (1a) and 7-ethylcamptothecin (1b) with 90% fuming nitric acid either neat or in acetic anhydride and then followed by I reduction of the resulting 14-nitrocamptothecins (2). 14-Aminocamptothecin (3a) and 7-ethyl-14-aminocamptothecin (313) demonstrated excellent cytotoxic potency against human tumor cell lines in vitro, and they are not substrates for any of the major clinically relevant efflux pumps (MDR1, MRP1, and BCRP). 3a and 3b showed similar cytotoxicity against human and mouse bone marrow progenitor cells. This is in contrast to many camptothecin analogues, which are substrates for efflux pumps and are dramatically more toxic to human marrow cells relative to murine. 3a and 3b demonstrated significant brain penetration when dosed orally in mice. 3b showed significantly better efficacy relative to topotecan when dosed orally in the three ectopic xenograft models, H460, HT29, and PC-3. On the basis of its favorable in vitro and in vivo profile, 3b warrants future development.