2-(4-amino-3-methylphenyl)-4-fluorobenzothiazole | 328087-12-3

• 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-amino-3-methylphenyl)-4-fluorobenzothiazole
• 英文别名: Benzenamine, 4-(4-fluoro-2-benzothiazolyl)-2-methyl-；4-(4-fluoro-1,3-benzothiazol-2-yl)-2-methylaniline
• CAS: 328087-12-3
• 化学式: C₁₄H₁₁FN₂S
• 分子量: 258.319
• InChiKey: ILHIPVYEKVGUKF-UHFFFAOYSA-N

物化性质

• 熔点：
  203-205 °C
• 沸点：
  440.1±55.0 °C(Predicted)
• 密度：
  1.329±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-甲基-4-硝基苯甲酰氯 在 劳森试剂 、 吡啶 、 六甲基磷酰三胺 、 sodium hydroxide 、 tin(ll) chloride 、 potassium hexacyanoferrate(III) 作用下， 以 乙醇 为溶剂， 反应 22.0h， 生成 2-(4-amino-3-methylphenyl)-4-fluorobenzothiazole
  参考文献：
  名称：

  Antitumor Benzothiazoles. 14. Synthesis and in Vitro Biological Properties of Fluorinated 2-(4-Aminophenyl)benzothiazoles

  摘要：

  Synthetic routes to a series of mono- and difluorinated 2-(4-amino-3-substituted-phenyl)benzothiazoles have been devised. Whereas mixtures of regioisomeric 5- and 7-fluorobenzothiazoles were formed from the established Jacobsen cyclization of precursor 3-fluorothiobenzanilides, two modifications to this general process have allowed the synthesis of pure samples of these target compounds. Fluorinated 2-(4-aminophenyl)benzothiazoles were potently cytotoxic (GI(50) < 1 nM) in vitro in sensitive human breast MCF-7 (ER+) and MDA 468 (ER-) cell lines but inactive (GI(50) > 10 muM) against PC 3 prostate, nonmalignant HBL 100 breast, and HCT 116 colon cells. The biphasic dose-response relationship characteristically shown by the benzothiazole series against sensitive cell lines was exhibited by the 4- and 6-fluorobenzothiazoles (10b,d) but not by the 5- and 7-fluoro-benzothiazoles (10h,i). The most potent broad spectrum agent in the NCI cell panel was 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (10h) which, unlike the g-fluoro isomer (10d), produces no exportable metabolites in the presence of sensitive MCF-7 cells. Induction of cytochrome P450 CYP1A1, a crucial event in determining the antitumor specificity of this series of benzothiazoles, was not compromised. 10h is currently the focus of pharmaceutical and preclinical development.

  DOI：

  10.1021/jm001104n

文献信息

• Substituted 2-arylbenzazole compounds and their use as antitumour agents
  申请人：Stevens Malcolm F. G.

  公开号：US06858633B1

  公开（公告）日：2005-02-22

  Substituted 2-phenylbenzazole compounds of formula (I) wherein X represents S or O and Q represents a direct bond, —CH2— or —CH═Ch—, exhibt selective antiproliferactive activity in respect of mammalian tumour cells. At least in preferred enbodiments the benzene ring of the benzazole nucleus has a halogen substituent, preferably flourine, and the 2-phenyl group has a 4′-amino substituent which may be conjugated with an amino acid to provide a water soluble amino acid amide prodrug or salt thereof.

  公式（I）中X代表S或O，Q代表直接键，—CH2—或—CH═CH—的2-苯基苯并唑化合物表现出对哺乳动物肿瘤细胞的选择性抗增殖活性。在至少首选实施例中，苯并唑核的苯环具有卤素取代基，优选是氟，并且2-苯基团具有4'-氨基取代基，可能与氨基酸共轭以提供水溶性氨基酸酰胺前药或其盐。
• [EN] SUBSTITUTED 2-ARYLBENZAZOLE COMPOUNDS AND THEIR USE AS ANTITUMOUR AGENTS<br/>[FR] COMPOSES DE 2-ARYLBENZAZOLE SUBSTITUES ET LEUR UTILISATION COMME AGENTS ANTITUMORAUX
  申请人：CANCER RES CAMPAIGN TECH

  公开号：WO2001014354A1

  公开（公告）日：2001-03-01

  Substituted 2-phenylbenzazole compounds of formula (I) wherein X represents S or O and Q represents a direct bond, -CH2- or -CH=CH-, exhibit selective antiproliferative activity in respect of mammalian tumour cells. At least in preferred embodiments the benzene ring of the benzazole nucleus has a halogen substituent, preferably fluorine, and the 2-phenyl group has a 4'-amino substituent which may be conjugated with an amino acid to provide a water soluble amino acid amide prodrug or salt thereof.

  公式（I）中的2-苯基苯并咪唑化合物，其中X代表S或O，Q代表直接键，-CH2-或-CH=CH-，在哺乳动物肿瘤细胞中表现出选择性抗增殖活性。在至少优选实施例中，苯并咪唑核的苯环具有卤素取代基，优选为氟，而2-苯基基团具有4'-氨基取代基，可以与氨基酸结合以提供水溶性氨基酸酰胺前药或其盐。
• SUBSTITUTED 2-ARYLBENZAZOLE COMPOUNDS AND THEIR USE AS ANTITUMOUR AGENTS
  申请人：Cancer Research Ventures Limited

  公开号：EP1204650B1

  公开（公告）日：2006-04-19
• US6858633B1
  申请人：——

  公开号：US6858633B1

  公开（公告）日：2005-02-22
• Antitumor Benzothiazoles. 14. Synthesis and in Vitro Biological Properties of Fluorinated 2-(4-Aminophenyl)benzothiazoles
  作者：Ian Hutchinson、Mei-Sze Chua、Helen L. Browne、Valentina Trapani、Tracey D. Bradshaw、Andrew D. Westwell、Malcolm F. G. Stevens

  DOI：10.1021/jm001104n

  日期：2001.4.1

  Synthetic routes to a series of mono- and difluorinated 2-(4-amino-3-substituted-phenyl)benzothiazoles have been devised. Whereas mixtures of regioisomeric 5- and 7-fluorobenzothiazoles were formed from the established Jacobsen cyclization of precursor 3-fluorothiobenzanilides, two modifications to this general process have allowed the synthesis of pure samples of these target compounds. Fluorinated 2-(4-aminophenyl)benzothiazoles were potently cytotoxic (GI(50) < 1 nM) in vitro in sensitive human breast MCF-7 (ER+) and MDA 468 (ER-) cell lines but inactive (GI(50) > 10 muM) against PC 3 prostate, nonmalignant HBL 100 breast, and HCT 116 colon cells. The biphasic dose-response relationship characteristically shown by the benzothiazole series against sensitive cell lines was exhibited by the 4- and 6-fluorobenzothiazoles (10b,d) but not by the 5- and 7-fluoro-benzothiazoles (10h,i). The most potent broad spectrum agent in the NCI cell panel was 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (10h) which, unlike the g-fluoro isomer (10d), produces no exportable metabolites in the presence of sensitive MCF-7 cells. Induction of cytochrome P450 CYP1A1, a crucial event in determining the antitumor specificity of this series of benzothiazoles, was not compromised. 10h is currently the focus of pharmaceutical and preclinical development.