2-(4'-Chloroacetamido-3-iodophenyl) benzothiazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 2-(4'-Chloroacetamido-3-iodophenyl) benzothiazole
• 英文别名: N-[4-(1,3-benzothiazol-2-yl)-2-iodophenyl]-2-chloroacetamide
• 化学式: C₁₅H₁₀ClIN₂OS
• 分子量: 428.681
• InChiKey: IUFQXRBKEMOZCO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  70.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-(2-苯并噻唑基)苯胺 在 一氯化碘 、 溶剂黄146 作用下， 以 苯 为溶剂， 反应 0.5h， 生成 2-(4'-Chloroacetamido-3-iodophenyl) benzothiazole
  参考文献：
  名称：

  Antitumor Benzothiazoles. 7. Synthesis of 2-(4-Acylaminophenyl)benzothiazoles and Investigations into the Role of Acetylation in the Antitumor Activities of the Parent Amines

  摘要：

  2-(4-Aminophenyl)benzothiazoles display potent and selective antitumor activity against inter alia breast, ovarian, colon, and renal cell lines, but their mechanism of action, though yet to be defined, may be novel. Metabolism is suspected to play a central role in the mode of action of these benzothiazoles since drug uptake and biotransformation were observed in sensitive cell lines (e.g., breast MCF-7 and MDA 468 cells) in vitro, whereas insensitive cell lines (e.g., prostate PC 3 cells) showed negligible uptake and biotransformation. N-Acyl derivatives of the arylamines have been synthesized, and in vitro studies confirm N-acetylation and oxidation as the main metabolic transformations of 2-(4-aminophenyl)benzothiazoles, with the predominant process being dictated by the nature of the 3'-substituent. The prototype amine 3 underwent mainly N-acetylation in vitro, while 3'-substituted analogues 4 and 5 were primarily oxidized. N-Acetylation of 4 to 11 exerts a drastic dyschemotherapeutic effect in vitro, but acetylation of the halogeno congeners 5-7 gave acetylamines 12-14 which substantially retain selective antitumor activity. In vivo pharmacokinetic studies in rats confirmed rapid and exclusive N-acetylation of the 3'-methyl analogue 4, but less acetylation with the 3'-chloro analogue 5. Distinct expression patterns of N-acetyltransferase NAT1 and NAT2 have been demonstrated in our panel of cell lines.

  DOI：

  10.1021/jm981076x

文献信息

• 2-arylbenzazole compounds
  申请人：Cancer Research Campaign Technology Limited

  公开号：US06034246A1

  公开（公告）日：2000-03-07

  There are disclosed herein 2-phenylbenzazole compounds having a 3'-substituent and a 4'-NR.sup.2 R.sup.6 substituent in the phenyl group where R.sup.5 and R.sup.6 are each hydrogen or alkyl, or where the $'-NR.sup.5 R.sup.6 substituent is N-acyl (or N-benzoyl). There are also disclosed 2-phenylbenzazole compounds in the form of 4'-N sulphamate salts. Such compounds exhibit significant selective cytotoxic activity in respect of tumor cells and provide potentially useful chemotherapeutic agents for selective treatment of a range of cancers.

  本文披露了含有3'-取代基和4'-NR.sup.2 R.sup.6取代基的2-苯基苯并咪唑化合物，其中苯基中的R.sup.5和R.sup.6分别为氢或烷基，或者4'-NR.sup.5 R.sup.6取代基为N-酰基（或N-苯甲酰基）。还披露了以4'-N磺酸盐形式存在的2-苯基苯并咪唑化合物。这些化合物在肿瘤细胞中表现出显著的选择性细胞毒活性，并为选择性治疗多种癌症提供了潜在有用的化疗药物。
• 2-ARYLBENZAZOLE COMPOUNDS
  申请人：Cancer Research Ventures Limited

  公开号：EP0812319B1

  公开（公告）日：2002-07-10
• US6034246A
  申请人：——

  公开号：US6034246A

  公开（公告）日：2000-03-07
• [EN] 2-ARYLBENZAZOLE COMPOUNDS<br/>[FR] COMPOSES 2-ARYLBENZAZOLE
  申请人：CANCER RESEARCH CAMPAIGN TECHNOLOGY LIMITED

  公开号：WO1996026932A1

  公开（公告）日：1996-09-06

  (EN) There are disclosed herein 2-phenylbenzazole compounds having a 3'-substituent and a 4'-NR5R6 substituent in the phenyl group where R5 and R6 are each hydrogen or alkyl, or where the 4'-NR5R6 substituent is N-acyl (or N-benzoyl). There are also disclosed 2-phenylbenzazole compounds in the form of 4'-N sulphamate salts. Such compounds exhibit significant selective cytotoxic activity in respect of tumor cells and provide potentially useful chemotherapeutic agents for selective treatment of a range of cancers.(FR) Cette invention concerne des composés 2-phénylbenzazole ayant un substituant en 3' et un substituant NR5R6 en 4' dans le groupe phényle, R5 et R6 étant chacun l'hydrogène ou un alkyle, ou le substituant NR5R6 en 4' étant un N-acyle (ou un N-benzoyle). L'invention se rapporte également à des composés 2-phényl-benzazole sous la forme de sels de sulphamate portant N en 4'. De tels composés présentent une activité cytotoxique sélective significative vis-à-vis des cellules tumorales et permettent de disposer d'agents chimiothérapeutiques potentiellement utiles pour le traitement sélectif d'un certain nombre de cancers.
• Antitumor Benzothiazoles. 7. Synthesis of 2-(4-Acylaminophenyl)benzothiazoles and Investigations into the Role of Acetylation in the Antitumor Activities of the Parent Amines
  作者：Mei-Sze Chua、Dong-Fang Shi、Samantha Wrigley、Tracey D. Bradshaw、Ian Hutchinson、P. Nicholas Shaw、David A. Barrett、Lesley A. Stanley、Malcolm F. G. Stevens

  DOI：10.1021/jm981076x

  日期：1999.2.1

  2-(4-Aminophenyl)benzothiazoles display potent and selective antitumor activity against inter alia breast, ovarian, colon, and renal cell lines, but their mechanism of action, though yet to be defined, may be novel. Metabolism is suspected to play a central role in the mode of action of these benzothiazoles since drug uptake and biotransformation were observed in sensitive cell lines (e.g., breast MCF-7 and MDA 468 cells) in vitro, whereas insensitive cell lines (e.g., prostate PC 3 cells) showed negligible uptake and biotransformation. N-Acyl derivatives of the arylamines have been synthesized, and in vitro studies confirm N-acetylation and oxidation as the main metabolic transformations of 2-(4-aminophenyl)benzothiazoles, with the predominant process being dictated by the nature of the 3'-substituent. The prototype amine 3 underwent mainly N-acetylation in vitro, while 3'-substituted analogues 4 and 5 were primarily oxidized. N-Acetylation of 4 to 11 exerts a drastic dyschemotherapeutic effect in vitro, but acetylation of the halogeno congeners 5-7 gave acetylamines 12-14 which substantially retain selective antitumor activity. In vivo pharmacokinetic studies in rats confirmed rapid and exclusive N-acetylation of the 3'-methyl analogue 4, but less acetylation with the 3'-chloro analogue 5. Distinct expression patterns of N-acetyltransferase NAT1 and NAT2 have been demonstrated in our panel of cell lines.