4β-[4-(4,6-dichloro-1,3-benzothiazole-2-yl)anilino]-4-desoxypodophyllotoxin | 1073610-42-0

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: 4β-[4-(4,6-dichloro-1,3-benzothiazole-2-yl)anilino]-4-desoxypodophyllotoxin
• 英文别名: 4β-[4"-(4",6"-dichloro-1",3"-benzothiazole-2"-yl)anilino]-4-desoxypodophyllotoxin；(5S,5aS,8aR,9R)-5-[4-(4,6-dichloro-1,3-benzothiazol-2-yl)anilino]-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one
• CAS: 1073610-42-0
• 化学式: C₃₅H₂₈Cl₂N₂O₇S
• 分子量: 691.589
• InChiKey: HFGCEKHKVUDISX-AOVYYMIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  47
• 可旋转键数：
  7
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-(4-aminophenyl)-4,6-dichlorobenzothiazole 、 鬼臼毒素 以70%的产率得到4β-[4-(4,6-dichloro-1,3-benzothiazole-2-yl)anilino]-4-desoxypodophyllotoxin
  参考文献：
  名称：

  NOVEL 4BETA-AMINO PODOPHYLLOTOXIN CONGENERS AS POTENTIAL ANTICANCER AGENTS AND A PROCESS FOR THE PREPARATION THEREOF

  摘要：

  本发明提供了一类新的4β-[4″-(1″,3″-苯并噻唑-2″-基)苯胺基]翠榆毒素类似物，其结构式如下所示（4）。其中R=H或CH3；R1=H、卤素、CH3；R2=H、卤素、OCH3。本发明还提供了一种制备新的4β-[4″-(1″,3″-苯并噻唑-2″-基)苯胺基]翠榆毒素类似物作为有效抗癌剂的方法。更具体地，它提供了一种制备翠榆毒素的4β-[4″-(1″,3″-苯并噻唑-2″-基)苯胺基]衍生物的方法。合成新翠榆毒素类似物作为抗癌剂的方法产生了翠榆毒素的新颖和立体选择性衍生物，其中这些类似物的合成关键步骤是通过对C-4β-碘中间体的直接亲核取代。4β-碘翠榆毒素与取代或未取代的4-(1,3-苯并噻唑-2-基)苯胺以立体选择性的方式反应，从而得到4β-[4″-(1″,3″-苯并噻唑-2″-基)苯胺基]翠榆毒素衍生物。

  公开号：

  US20080275248A1

文献信息

• An efficient one-pot synthesis of benzothiazolo-4β-anilino-podophyllotoxin congeners: DNA topoisomerase-II inhibition and anticancer activity
  作者：Ahmed Kamal、B. Ashwini Kumar、Paidakula Suresh、Nagula Shankaraiah、M. Shiva Kumar

  DOI：10.1016/j.bmcl.2010.11.002

  日期：2011.1

  An efficient one-pot iodination methodology for the synthesis of benzothiazolo-4 beta-anilino-podophyllotoxin (5a-h) and benzothiazolo-4 beta-anilino-4-O-demethylepipodophyllotoxin (6a-h) congeners has been successfully developed by using zirconium tetrachloride/sodium iodide. Interestingly, this protocol demonstrates enhancement of stereoselectivity apart from the improvement in the yields in comparison to previous methods reported for such related podophyllotoxin derivatives. These compounds have been designed and synthesized using association strategy by coupling of 4 beta-podophyllotoxin and 4 beta-demethylepipodophyllotoxin with a variety of substituted aminoaryl benzothiazoles. Some of the representative compounds have been evaluated for their cytotoxicity against selected human cancer cell lines and DNA topoisomerase-II inhibition activity. (C) 2010 Elsevier Ltd. All rights reserved.
• US7960418B2
  申请人：——

  公开号：US7960418B2

  公开（公告）日：2011-06-14
• [EN] NOVEL 4ß-AMINO PODOPHYLLOTOXIN CONGENERS AS POTENTIAL ANTICANCER AGENTS AND A PROCESS FOR THE PREPARATION THEREOF<br/>[FR] NOUVEAUX CONGÉNÈRES DE 4?-AMINO PODOPHYLLOTOXINE UTILISÉS COMME AGENTS ANTI-CANCEREUX POTENTIELS ET LEUR PROCÉDÉ DE PRÉPARATION
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2008136018A2

  公开（公告）日：2008-11-13

  [EN] The present invention provides new class of 4ß-[4"-(1", 3"-benzothiazole-2"-yl) anilino] podophyllotoxin analogues having the structural formula (4) as follows. Where R = H or CH₃; R₂ = H, halogen, CH₃ and R₂ = H1 halogen, OCH3. The present invention also provides a process for the preparation of new 4ß- [4"-(1", 3"-benzothiazole-2"-yl) anilino] podophyllotoxin analogues as useful anticancer agents. More particularly, it provides a process for the preparation of 4ß- [4"-(1", 3"-benzothiazoIe-2"-yl) anilino] derivatives of podophyllotoxin. The process for the synthesis of new podophyllotoxin analogues as anticancer agents produces the novel and stereo-selective derivatives of the podophyllotoxin in good yields, where in the key step for the synthesis of these analogues is by direct nucleophilic substitution of C-4ß-iodo intermediates. The 4ß-iodopodophyllotoxin, which has been reacted with substituted or unsubstituted 4-(1,3-benzothiazole-2-yl) aniline in a stereo-selective manner to afford the 4ß-[4"-(1", 3"-benzothiazole-2"-yl) anilino] derivatives of podophyllotoxin.
  [FR] La présente invention concerne une nouvelle classe d'analogues de 4ß-[4'-(1', 3'-benzothiazole-2'-yl) anilino] podophyllotoxine représentée par la formule structurale (4) dans laquelle R = H ou CH₃ ; R₂ = H, halogène, CH₃ et R₂ = H1, halogène, OCH3. La présente invention concerne également un procédé pour la préparation de nouveaux analogues de 4ß- [4'-(1', 3'-benzothiazole-2'-yl) anilino] podophyllotoxine utilisés comme agents anti-cancéreux. L'invention concerne plus particulièrement un procédé pour la préparation de dérivés 4ß- [4'-(1', 3'-benzothiazoIe-2'-yl) anilino] de podophyllotoxine. Le procédé pour la synthèse de nouveaux analogues de podophyllotoxine utilisés comme agents anti-cancéreux produit les nouveaux dérivés stéréo-sélectifs de la podophyllotoxine avec de bons rendements, l'étape clé pour la synthèse de ces analogues étant la substitution nucléophile directe d'intermédiaires C-4ß-iodo. L'invention concerne également la 4ß-iodopodophyllotoxine, qui a été amenée à réagir avec une 4-(1,3-benzothiazole-2-yl) aniline substituée ou non substituée de façon stéréo-sélective pour produire les dérivés 4ß-[4'-(1', 3'-benzothiazole-2'-yl) anilino] de la podophyllotoxine.
• NOVEL 4BETA-AMINO PODOPHYLLOTOXIN CONGENERS AS POTENTIAL ANTICANCER AGENTS AND A PROCESS FOR THE PREPARATION THEREOF
  申请人：Ahmed Kamal

  公开号：US20080275248A1

  公开（公告）日：2008-11-06

  The present invention provides new class of 4β-[4″-(1″,3″-benzothiazole-2″-yl)anilino]podophyllotoxin analogues having the structural formula as follows (4). Where R═H or CH 3 ; R 1 ═H, halogen, CH 3 and R 2 ═H, halogen, OCH 3 . The present invention also provides a process for the preparation of new 4β-[4″-(1″, 3″-benzothiazole-2″-yl)anilino]podophyllotoxin analogues as useful anticancer agents. More particularly, it provides a process for the preparation of 4β-[4″-(1″,3″-benzothiazole-2″-yl)anilino] derivatives of podophyllotoxin. The process for the synthesis of new podophyllotoxin analogues as anticancer agents produces the novel and stereo-selective derivatives of the podophyllotoxin in good yields, where in the key step for the synthesis of these analogues is by direct nucleophilic substitution of C-4β-iodo intermediates. The 4β-iodopodophyllotoxin, which has been reacted with substituted or unsubstituted 4-(1,3-benzothiazole-2-yl)aniline in a stereo-selective manner to afford the 4β-[4″-(1″,3″-benzothiazole-2″-yl)anilino] derivatives of podophyllotoxin.

  本发明提供了一类新的4β-[4″-(1″,3″-苯并噻唑-2″-基)苯胺基]翠榆毒素类似物，其结构式如下所示（4）。其中R=H或CH3；R1=H、卤素、CH3；R2=H、卤素、OCH3。本发明还提供了一种制备新的4β-[4″-(1″,3″-苯并噻唑-2″-基)苯胺基]翠榆毒素类似物作为有效抗癌剂的方法。更具体地，它提供了一种制备翠榆毒素的4β-[4″-(1″,3″-苯并噻唑-2″-基)苯胺基]衍生物的方法。合成新翠榆毒素类似物作为抗癌剂的方法产生了翠榆毒素的新颖和立体选择性衍生物，其中这些类似物的合成关键步骤是通过对C-4β-碘中间体的直接亲核取代。4β-碘翠榆毒素与取代或未取代的4-(1,3-苯并噻唑-2-基)苯胺以立体选择性的方式反应，从而得到4β-[4″-(1″,3″-苯并噻唑-2″-基)苯胺基]翠榆毒素衍生物。