2-(4-amino-3-iodophenyl)-6-methoxybenzothiazole | 178804-17-6

• 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-iodophenyl)-6-methoxybenzothiazole
• 英文别名: 2-(3'-iodo-4'-aminophenyl)-6-methoxybenzothiazole；2-(4'-Amino-3'-iodophenyl)-6-methoxybenzothiazole；2-iodo-4-(6-methoxy-1,3-benzothiazol-2-yl)aniline
• CAS: 178804-17-6
• 化学式: C₁₄H₁₁IN₂OS
• 分子量: 382.225
• InChiKey: GNPIDHOWIOQMKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  76.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-amino-3-iodophenyl)-6-methoxybenzothiazole 在 三溴化硼 、 三乙胺 、 copper(l) chloride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 Acetic acid 2-(4-acetylamino-3-chloro-phenyl)-benzothiazol-6-yl ester
  参考文献：
  名称：

  Antitumor Benzothiazoles. 8. Synthesis, Metabolic Formation, and Biological Properties of the C- and N-Oxidation Products of Antitumor 2-(4-Aminophenyl)benzothiazoles

  摘要：

  2-(4-Aminophenyl)benzothiazoles 1 and their N-acetylated forms have been converted to C- and N-hydroxylated derivatives to investigate the role of metabolic oxidation in the mode of action of this series of compounds. 2-(4-Amino-3-methylphenyl)benzothiazole (1a, DF 203, NSC 674495) is a novel and potent antitumor agent with selective growth inhibitory properties against human cancer cell lines. Very low IC50 values (<0.1 mu M) were encountered in the most sensitive breast cancer cell lines, MCF-7 and T-47D, whereas renal cell line TK-10 was weakly inhibited by la. Cell lines from the same tissue origin, MDA-MB-435 (breast), CAKI-1 (renal), and A498 (renal), were insensitive to 1a. Accumulation and metabolism of la were observed in sensitive cell lines only, with the highest rate of metabolism occurring in the most sensitive MCF-7 and T-47D cells. Thus, differential uptake and metabolism of 1a by cancer cell lines may underlie its selective profile of anticancer activity. A major metabolite in these sensitive cell lines has been identified as 2-(4-amino-3-methylphenyl)-6-hydroxybenzothiazole (6c). Hydroxylation of 1a was not detected in the homogenate of previously untreated MCF-7, T-47D, and TK-10 cells but was readily observed in homogenates of sensitive cells that were pretreated with 1a. Accumulation and covalent binding of [C-14]1a derived radioactivity was observed in the sensitive MCF-7 cell line but not in the insensitive MDA-MB-435 cell line. The mechanism of growth inhibition by 1a, which is unknown, may be dependent on the differential metabolism of the drug to an activated form by sensitive cell Lines only and its covalent binding to an intracellular protein. However, the 6-hydroxy derivative 6c is not the 'active' metabolite since, like all other C- and N-hydroxylated benzothiazoles examined in this study, it is devoid of antitumor properties in vitro.

  DOI：

  10.1021/jm990104o
• 作为产物：
  描述：

  6-甲氧基-2-(4-硝基苯基)苯并噻唑 在 一氯化碘 、 溶剂黄146 、 tin(ll) chloride 作用下， 以 乙醇 为溶剂， 反应 7.5h， 生成 2-(4-amino-3-iodophenyl)-6-methoxybenzothiazole
  参考文献：
  名称：

  Antitumor Benzothiazoles. 3. Synthesis of 2-(4-Aminophenyl)benzothiazoles and Evaluation of Their Activities against Breast Cancer Cell Lines in Vitro and in Vivo

  摘要：

  A new series of 2-(4-aminophenyl)benzothiazoles substituted in the phenyl ring and benzothiazole moiety has been synthesized by simple, high-yielding routes. The parent molecule 5a shows potent inhibitory activity in vitro in the nanomolar range against a panel of human breast cancer cell lines, but is inactive (IC50 > 30 mu M) against other cell types: activity against the sensitive breast lines MCF-7 and MDA 468 is characterized by a biphasic dose-response relationship. Structure-activity relationships derived using these cell types has revealed that activity follows the heterocyclic sequence benzothiazole > benzoxazole much greater than benzimidazole and that 2-(4-aminophenyl)benzothiazoles bearing a 3'-methyl- 9a, 3'-bromo- 9c, 3'- iodo- 9f, and 3'-chloro-substituent 9i are especially potent and their activity extends to ovarian, lung, and renal cell lines. Four compounds have been evaluated in vivo against human mammary carcinoma models in nude mice. Compound 9a showed the most potent growth inhibition against the ER(+) (MCF-7 and BO) and ER(-) (MT-1 and MT-3) tumors. Our efforts to identify a pharmacological mechanism of action for these intriguing compounds have not, as yet, been successful.

  DOI：

  10.1021/jm9600959

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。
• Thioflavin derivatives for use in antemortem diagnosis of Alzheimer's disease and in vivo imaging and prevention of amyloid deposition
  申请人：UNIVERSITY OF PITTSBURGH

  公开号：US20030236391A1

  公开（公告）日：2003-12-25

  This invention relates to novel thioflavin derivatives, methods of using the derivatives in, for example, in vivo imaging of patients having neuritic plaques, pharmaceutical compositions comprising the thioflavin derivatives and method of synthesizing the compounds. The compounds find particular use in the diagnosis and treatment of patients having diseases where accumulation of neuritic plaques are prevalent. The disease states or maladies include but are not limited to Alzheimer's disease, familial Alzheimer's disease, Down's Syndrome and homozygotes for the apolipoprotein E4 allele.

  这项发明涉及新型噻吩染料衍生物，以及使用这些衍生物进行例如体内成像患有神经节细胞斑块的患者、包含这些噻吩染料衍生物的药物组合物和合成这些化合物的方法。这些化合物在诊断和治疗患有神经节细胞斑块积聚病变的患者中具有特殊用途。这些疾病状态或疾病包括但不限于阿尔茨海默病、家族性阿尔茨海默病、唐氏综合症和载有apolipoprotein E4等位基因的纯合子。
• [EN] A METHOD OF DIAGNOSING PRODROMAL FORMS OF DISEASES ASSOCIATED WITH AMYLOID DEPOSITION<br/>[FR] PROCÉDÉ DE DIAGNOSTIC DE FORMES PRODROMIQUES DE MALADIES ASSOCIÉES AU DÉPÔT AMYLOÏDE
  申请人：UNIV PITTSBURGH

  公开号：WO2006014382A1

  公开（公告）日：2006-02-09

  A method of identifying a patient as prodromal to a disease associated with amyloid deposition by imaging techniques is provided. In addition, a method of identifying amyloid deposition diseases in patients who present with a dementing disorder of questionable etiology by imaging techniques is provided. The methods discloses substances which are used for imaging and generating data which can be used to determine progress of an asymptomatic patient to a disease associated with amyloid deposition. or to identify amyloid deposition diseases in patients who present with a dementing disorder of questionable etiology.

  提供了一种通过成像技术将患者识别为与淀粉样沉积相关的疾病的前驱的方法。此外，还提供了一种通过成像技术识别出患有疑似病因的痴呆症状的患者中存在淀粉样沉积疾病的方法。该方法公开了用于成像和生成数据的物质，这些数据可用于确定无症状患者发展为与淀粉样沉积相关的疾病的进展，或者用于识别出患有疑似病因的痴呆症状的患者中存在淀粉样沉积疾病。
• In Vivo or in Vitro Method For Detecting Amyloid Deposits Having at Least One Amyloidogenic Protein
  申请人：Klunk William E.

  公开号：US20080305040A1

  公开（公告）日：2008-12-11

  An amyloid deposit can be detected by administering to a subject or applying to a sample a compound of Formula (I) or Formula (II) or structures 1-45, as described, and then imaging to detect binding of the compound to an amyloid deposit, where the amyloido genie protein of the deposit can be AL, AH, ATTR, Aβ2M, AA, AApoAI, AApoAII, AGeI, ALys, AFib, ACys, ABri, ADan, APrP, ACaI, AlAPP, AANF, APro, AIns, AMed, AKer, A(tbn), and/or ALac.

  通过向受试者施用或将化合物I式或II式或结构1-45应用于样本，并进行成像以检测化合物与淀粉样沉积物的结合，可以检测到淀粉样沉积物。其中，沉积物的淀粉基因蛋白可以是AL、AH、ATTR、Aβ2M、AA、AApoAI、AApoAII、AGeI、ALys、AFib、ACys、ABri、ADan、APrP、ACaI、AlAPP、AANF、APro、AIns、AMed、AKer、A(tbn)和/或ALac。
• [EN] BENZOTHIAZOLE DERIVATIVE COMPOUNDS, COMPOSITIONS AND USES<br/>[FR] COMPOSES DERIVES DE BENZOTHIAZOLE, COMPOSITIONS ET UTILISATIONS
  申请人：UNIV PITTSBURGH

  公开号：WO2004083195A1

  公开（公告）日：2004-09-30

  This invention provides benzothiazole derivative compounds, compositions comprising such compounds, methods of preparing such compounds, and methods of using such compounds for detecting amyloid deposit(s) and for diagnosing a disease, disorder or condition characterized by amyloid deposit(s). The compounds find particular use in the diagnosis and treatment of patients having diseases where accumulation of neuritic plaques are prevalent. The disease states or maladies include but are not limited to Alzheimer's disease, familial Alzheimer's disease, Down's Syndrome and homozygotes for the apolipoprotein E4 allele.

  该发明提供了苯并噻唑衍生物化合物、包含这些化合物的组合物、制备这些化合物的方法，以及使用这些化合物检测淀粉样沉积物和诊断由淀粉样沉积物引起的疾病、紊乱或情况的方法。这些化合物特别适用于诊断和治疗患有神经元斑块积累的疾病的患者。这些疾病状态或病症包括但不限于阿尔茨海默病、家族性阿尔茨海默病、唐氏综合症和载脂蛋白E4等位基因纯合子。