(19S)-19-ethyl-7,12,19-trihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaene-14,18-dione | 200553-21-5

• 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: (19S)-19-ethyl-7,12,19-trihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaene-14,18-dione
• CAS: 200553-21-5
• 化学式: C₂₀H₁₆N₂O₆
• 分子量: 380.357
• InChiKey: ZBMBAPDNKSBROJ-OZBJMMHXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  28
• 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：
  120
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (19S)-19-ethyl-7,12,19-trihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaene-14,18-dione 在 吡啶 、 氢氧化钾 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 24.0h， 生成 2-[(19S)-19-ethyl-7,19-dihydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaen-12-yl]acetic acid
  参考文献：
  名称：

  Novel C-ring analogues of 20(S)-camptothecin-part-2: Synthesis and cytotoxicity of 5-C-substituted 20(S)-camptothecin analogues

  摘要：

  A series of 5-C-substituted 20(S)-camptothecin analogues were synthesised and evaluated their in vitro anti-cancer activity. Several of these analogues have showed excellent activity against human tumor cell lines. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00268-1
• 作为产物：
  描述：

  10-羟基喜树碱 在 盐酸 、 硫酸 、 三氯化铁 作用下， 以 乙醇 为溶剂， 反应 40.0h， 生成 (19S)-19-ethyl-7,12,19-trihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaene-14,18-dione
  参考文献：
  名称：

  20（S）-喜树碱的新型C环类似物。第3部分：A环，B环和C环类似物的合成及其体外细胞毒性。

  摘要：

  通过半合成制备了几种具有A环和B环取代基的5-取代的烷氧基20（S）-喜树碱类似物。根据获得的针对人肿瘤细胞系的体外细胞毒性数据，发现这些化合物中的大多数都具有有效的抗癌活性。

  DOI：

  10.1016/s0960-894x(00)00005-6

文献信息

• [EN] NOVEL WATER-SOLUBLE C-RING ANALOGUES OF 20 (S)-CAMPTOTHECIN<br/>[FR] NOUVEAUX ANALOGUES DE NOYAUX C HYDROSOLUBLES DE 20(S)-CAMPTOTHECINE
  申请人：DR. REDDY'S RESEARCH FOUNDATION

  公开号：WO1997046563A1

  公开（公告）日：1997-12-11

  (EN) Novel water-soluble C-ring analogues of 20(S)-camptothecin having general formula (1). All the compounds of formula (1) are prepared from the compounds of general formula (2) having 20(S)-chiral carbon where R1 to R5 have the meaning given above. The compounds of formula (1) possess potent anti-cancer and anti-viral properties. The invention also provides an alternate process for the preparation of known C-5 substituted compounds of formula (1).(FR) Nouveaux analogues de noyaux C hydrosolubles de 20(S)-camptothécine ayant la formule générale (1). Tous les composés de la formule (1) sont préparés à aprtir des composés de la formule générale (2) présentant un carbone 20(S)-chiral dans laquelle R1 à R5 ont la notation donnée dans la description. Les composés de la formule (1) présentent des propriétés anticancéreuses et antivirales puissantes. L'invention concerne également un autre procédé de préparation de composés à substitution C-5 connus de la formule (1).

  （中）具有一般式（1）的20（S）-喜树碱C环类似物的新型水溶性衍生物。所有式（1）的化合物均由具有20（S）-手性碳的通式（2）的化合物制备，其中R1至R5具有上述给定的含义。式（1）的化合物具有强效的抗癌和抗病毒性能。本发明还提供了一种用于制备已知的式（1）的C-5取代化合物的替代方法。
• Camptothecin derivatives, processes for preparing same, formulations containing such derivatives and their use
  申请人：KABUSHIKI KAISHA YAKULT HONSHA

  公开号：EP0074256A1

  公开（公告）日：1983-03-16

  New camptothecin derivatives possessing high anti-tumor activity and slight toxicity are represented by the general fnrmula: wherein R' is a hydrogen atom, an alkyl group, a hydroxyl group, an alkoxy group or an acyloxy group, R2 is a hydrogen atom, an alkyl group, an aralkyl group, a hydroxymethyl group, a carboxymethyl group or an acyloxymethyl group, and R3 is the grouping -XR' (in which a hydrogen atom, an alkyl group or an acyl group and X is an oxygen atom or a sulfur atom), a nitro group, an amino group, an alkylamino group, an acylamino group or a halogen atom, with the proviso that when R' and R2 are both hydrogen atoms, R3 is not a hydroxyl group, methoxy group or acetoxy group. Such derivatives may be prepared by treating a 5-R1-7-R2- camptothecin derivative with a peroxidant and then reacting the resultant 5-R'-7-R2-camptothecin-1-oxide with an active hydrogen compound under irradiation with UV-rays or by catalytically hydrogenating the ring B of camptothecin in a solvent, treating the resultant tetrahydro product with an acylating agent, introducing a nitro group into the 10- position of the acylated product by reaction with nitric acid, splitting off the acyl group in the 10-nitro product by hydrolysis and treating the hydrolyzed tetrahydro product with an oxidizing agent for dehydrogenation, and if desired, reducing the nitro group in the resultant product to amino group and modifying the amino group by N-alkylation, N-acylation or by diazotization followed by hydrolysis or a Sandmeyer reaction, before or after oxidation of the 10-nitro- tetrahydro product.

  具有高抗肿瘤活性和轻微毒性的喜树碱新衍生物由通式表示： 其中，R'是氢原子、烷基、羟基、烷氧基或酰氧基；R2是氢原子、烷基、芳基、羟甲基、羧甲基或酰氧基；R3是基团-XR'（其中氢原子、烷基或酰基和X是氧原子或硫原子）、R'和 R2 都是氢原子时，R3 不是羟基、甲氧基或乙酰氧基。此类衍生物的制备方法如下：用过氧化物处理 5-R1-7-R2- 喜树碱衍生物，然后在紫外线照射下使生成的 5-R'-7-R2 喜树碱-1-氧化物与活性氢化合物反应，或者在溶剂中催化喜树碱环 B 的氢化，用酰化剂处理生成的四氢产物，通过与硝酸反应在酰化产物的 10-位引入硝基、在 10-硝基-四氢产物氧化之前或之后，通过水解将 10-硝基产物中的酰基分 离，并用氧化剂处理水解后的四氢产物以进行脱氢，如果需要，将所得产物中 的硝基还原为氨基，并通过 N-烷基化、N-酰基化或重氮化修饰氨基，然后进行水 解或桑德迈尔反应。
• Novel water soluble c-ring analogues of 20 (s)-camptothecin
  申请人：DR. REDDY'S RESEARCH FOUNDATION

  公开号：EP1138682A1

  公开（公告）日：2001-10-04

  Novel water-soluble C-ring analogues of 20(s)-camptothecin having general formula (1). All the compounds of formula (1) are prepared from the compounds of general formula (2) having 20(s)-chiral carbon where R1 to R5 have the meaning given above. The compounds of formula (1) possess potent anti-cancer and anti-viral properties. The invention also provides an alternate process for the preparation of known C-5 substituted compounds of formula (1).

  具有通式(1)的 20(s)-喜树碱的新型水溶性 C 环类似物。所有的式(1)化合物均由具有 20(s)-手性碳的通式(2)化合物制备而成，其中 R1 至 R5 具有上述含义。式（1）化合物具有强效的抗癌和抗病毒特性。本发明还提供了制备已知 C-5 取代的式 (1) 化合物的另一种工艺。
• New Method for the Synthesis of 5‐Hydroxycamptothecin Derivatives
  作者：Xungui He、Heyong Gao、Wei Lu、Junchao Cai

  DOI：10.1081/scc-200039356

  日期：2004.12.31

  An efficient hydroxylation at the 5-position of the C ring of camptothecins was accomplished with the complex of CuI and organic amines as catalyst in the presence of oxygen at room temperature in dimethyl formate (DMF). To be successfully hydroxylated. the insoluble camptothecin analogue was transformed to the corresponding 20 carbonates.
• WATER-SOLUBLE C-RING ANALOGUES OF 20 (S)-CAMPTOTHECIN
  申请人：DR. REDDY'S RESEARCH FOUNDATION

  公开号：EP0847397B1

  公开（公告）日：2002-09-04