5,7-dimethoxy-2-(4'-fluorophenyl)-1,3-benzothiazole | 817553-13-2

• 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: 5,7-dimethoxy-2-(4'-fluorophenyl)-1,3-benzothiazole
• 英文别名: 2-(4-fluorophenyl)-5,7-dimethoxy-1,3-benzothiazole
• CAS: 817553-13-2
• 化学式: C₁₅H₁₂FNO₂S
• 分子量: 289.33
• InChiKey: FQUKHOWWEDWMLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  59.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5,7-dimethoxy-2-(4'-fluorophenyl)-1,3-benzothiazole 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以88%的产率得到5,7-dihydroxy-2-(4'-fluorophenyl)-1,3-benzothiazole
  参考文献：
  名称：

  Synthesis and Evaluation of ¹⁸F-Labeled 2-Phenylbenzothiazoles as Positron Emission Tomography Imaging Agents for Amyloid Plaques in Alzheimer’s Disease

  摘要：

  Imaging agents targeting amyloid beta(A beta) may be useful for early diagnosis and follow-up of treatment of patients with Alzheimer's disease (AD). Three of five tested 2-(4'-fluorophenyl)-1,3-benzothiazoles displayed high binding affinities for A beta plaques in AD human brain homogenates (K-i between 2.2 and 22.5 nM). They all contained the F-18-label directly attached to the aromatic ring and were synthesized starting from the nitro precursor. Determination of the partition coefficient, biodistribution studies in normal mice, and in vivo mu PET studies in normal rats showed that their initial brain uptake was high and brain washout was fast. The most promising compound [F-18]5, or 6- methyl-2-(4'-[F-18]fluorophenyl)-1,3-benzothiazole, seemed to be metabolically stable in the brain, and its plasma radiometabolites, which do not cross the blood-brain barrier, were determined. The preliminary results strongly suggest that this new fluorinated compound is a promising candidate as an A beta plaque imaging agent for the study of patients with AD.

  DOI：

  10.1021/jm8013376
• 作为产物：
  描述：

  N-3',5'-dimethoxyphenyl-4-fluorothiobenzamide 在 potassium hexacyanoferrate(III) 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以45%的产率得到5,7-dimethoxy-2-(4'-fluorophenyl)-1,3-benzothiazole
  参考文献：
  名称：

  Synthesis and Evaluation of ¹⁸F-Labeled 2-Phenylbenzothiazoles as Positron Emission Tomography Imaging Agents for Amyloid Plaques in Alzheimer’s Disease

  摘要：

  Imaging agents targeting amyloid beta(A beta) may be useful for early diagnosis and follow-up of treatment of patients with Alzheimer's disease (AD). Three of five tested 2-(4'-fluorophenyl)-1,3-benzothiazoles displayed high binding affinities for A beta plaques in AD human brain homogenates (K-i between 2.2 and 22.5 nM). They all contained the F-18-label directly attached to the aromatic ring and were synthesized starting from the nitro precursor. Determination of the partition coefficient, biodistribution studies in normal mice, and in vivo mu PET studies in normal rats showed that their initial brain uptake was high and brain washout was fast. The most promising compound [F-18]5, or 6- methyl-2-(4'-[F-18]fluorophenyl)-1,3-benzothiazole, seemed to be metabolically stable in the brain, and its plasma radiometabolites, which do not cross the blood-brain barrier, were determined. The preliminary results strongly suggest that this new fluorinated compound is a promising candidate as an A beta plaque imaging agent for the study of patients with AD.

  DOI：

  10.1021/jm8013376

文献信息

• Product comprising at least one phosphatase cdc25 inhibitor combined with at least one other anticancer agent
  申请人：Prevost Gregoire

  公开号：US20060281736A1

  公开（公告）日：2006-12-14

  A subject of the invention is a product comprising at least one Cdc25 phosphatase inhibitor in combination with at least one other anti-cancer agent for a therapeutic use which is simultaneous, separate or spread over time in the treatment of cancer. According to the invention, the other anti-cancer agent is preferably chosen from: analogues of DNA bases such as 5-fluorouracil; Type I and/or II topoisomerase inhibitors such as for example camptothecin and its analogues, doxorubicin or amsacrine; compounds interacting with the cell spindle such as for example paclitaxel (Taxol); compounds acting on the cytoskeleton such as vinblastine; inhibitors of the transduction of the signal passing through the heterotrimeric G proteins; prenyltransferase inhibitors, and in particular farnesyltransferase inhibitors; cyclin-dependent kinase (CDKs) inhibitors; alkylating agents such as cisplatin; antagonists of folic acid such as methotrexate; and inhibitors of the synthesis of DNA and cell division cell such as mitomycin C. A further subject of the invention is (1R)-1-[((2R)-2-amino-3-[(8S)-8-(cyclohexylmethyl)-2-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]-3-oxopropyl}dithio)methyl]-2-[(8S)-8-(cyclohexylmethyl)-2-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8B)-yl]-2-oxoethylamine, or a pharmaceutically acceptable salt thereof, useful as an anticancer agent.

  本发明的一个主题是一种产品，包括至少一种Cdc25磷酸酶抑制剂与至少一种其他抗癌药物的组合，用于治疗癌症，治疗可以同时进行、分开进行或随时间推移进行。根据本发明，其他抗癌药物优选从以下选择：DNA碱基类似物，如5-氟尿嘧啶；I型和/或II型拓扑异构酶抑制剂，例如紫杉醇及其类似物、阿霉素或阿马曲辛；与细胞纺锤相互作用的化合物，例如紫杉醇（紫杉醇）；作用于细胞骨架的化合物，如长春碱；通过异三聚体G蛋白传递的信号的抑制剂；前尾转移酶抑制剂，特别是法尼基转移酶抑制剂；细胞周期蛋白依赖性激酶（CDKs）抑制剂；碱化剂，如顺铂；叶酸拮抗剂，如甲氨蝶呤；以及DNA合成和细胞分裂细胞的抑制剂，如丝裂霉素C。本发明的另一个主题是（1R）-1-[((2R)-2-氨基-3-[(8S)-8-(环己甲基)-2-苯基-5,6-二氢咪唑[1,2-a]吡嗪-7(8H)-基]-3-氧代丙基}二硫)甲基]-2-[(8S)-8-(环己甲基)-2-苯基-5,6-二氢咪唑[1,2-a]吡嗪-7(8B)-基]-2-氧代乙基胺，或其药学上可接受的盐，用作抗癌剂。
• Benzothiazole-4,7-diones and benzoxazole-4,7-diones with substituents in position 5 or 6 and method for production thereof
  申请人：Galcera Contour Marie-Odile

  公开号：US20060135573A1

  公开（公告）日：2006-06-22

  A subject of the invention is a selective process for the preparation of derivatives of benzothiazole-4,7-diones and benzoxazole-4,7-diones monosubstituted in position 5 or in position 6 by an amino group itself optionally substituted. Said derivatives are inhibitors of the Cdc25 phosphatases and can be used for preparing medicaments intended to treat cancer. The invention also offers synthesis intermediates which are useful in implementing the process of the invention. The invention also relates in particular to the following derivatives of benzothiazole-4,7-diones: 2-(2-chloro-6-fluorophenyl)-5-[2-(dimethylamino)ethyl]amino}-1,3-benzothiazole-4,7-dione; 2-(2-chloro-6-fluorophenyl)-5-[(2-pyrrolidin-1-ylethyl)amino]-1,3-benzothiazole-4,7-dione.

  本发明的一个主题是一种选择性过程，用于制备在5位或6位位置由氨基团单取代的苯并噻唑-4,7-二酮和苯并噁唑-4,7-二酮衍生物。所述衍生物是Cdc25磷酸酯酶的抑制剂，可用于制备用于治疗癌症的药物。该发明还提供了在实施该发明过程中有用的合成中间体。该发明还特别涉及苯并噻唑-4,7-二酮的以下衍生物：2-(2-氯-6-氟苯基)-5-[2-(二甲基氨基)乙基]氨基}-1,3-苯并噻唑-4,7-二酮；2-(2-氯-6-氟苯基)-5-[(2-吡咯啉-1-基乙基)氨基]-1,3-苯并噻唑-4,7-二酮。
• Product comprising at least one Cdc25 phosphatase inhibitor in combination with at least one other anti-cancer agent
  申请人：Provost Gregoire

  公开号：US20090253685A1

  公开（公告）日：2009-10-08

  A subject of the invention is a product comprising at least one Cdc25 phosphatase inhibitor in combination with at least one other anti-cancer agent for a therapeutic use which is simultaneous, separate or spread over time in the treatment of cancer. According to the invention, the other anti-cancer agent is preferably chosen from: analogues of DNA bases such as 5-fluorouracil; Type I and/or II topoisomerase inhibitors such as for example camptothecin and its analogues, doxorubicin or armsacrine; compounds interacting with the cell spindle such as for example paclitaxel (Taxol); compounds acting on the cytoskeleton such as vinblastine; inhibitors of the transduction of the signal passing through the heterotrimeric G proteins; prenyltransferase inhibitors, and in particular farnesyltransferase inhibitors; cyclin-dependent kinase (CDKs) inhibitors; alkylating agents such as cisplatin; antagonists of folic acid such as methotrexate; and inhibitors of the synthesis of DNA and cell division cell such as mitomycin C. A further subject of the invention is (1R)-1-[((2R)-2-amino-3-[(8S)-8-(cyclohexylmethyl)-2-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]-3-oxopropyl}dithio)methyl]-2-[(8S)-8-(cyclohexylmethyl)-2-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]-2-oxoethylamine, or a pharmaceutically acceptable salt thereof, useful as an anticancer agent.

  本发明的一个主题是一种产品，其包含至少一种Cdc25磷酸酶抑制剂和至少一种其他抗癌药物的组合，用于治疗癌症的同时、分离或时间延长的治疗。根据本发明，其他抗癌药物优选从以下选择：DNA碱基类似物，例如5-氟尿嘧啶；I型和/或II型拓扑异构酶抑制剂，例如伯氨喹、多柔比星或阿姆沙曲；与细胞纺锤相互作用的化合物，例如紫杉醇（紫杉醇）；作用于细胞骨架的化合物，例如长春新碱；通过异源三聚体G蛋白传递信号的抑制剂；戊二烯基转移酶抑制剂，特别是戊二烯基转移酶抑制剂；细胞周期蛋白依赖性激酶（CDKs）抑制剂；碱基化剂，例如顺铂；叶酸拮抗剂，例如甲氨蝶呤；以及DNA合成和细胞分裂细胞的抑制剂，例如丝裂霉素C。本发明的另一个主题是（1R）-1-[（（2R）-2-氨基-3-[(8S)-8-（环己基甲基）-2-苯基-5,6-二氢咪唑[1,2-a]吡嗪-7（8H）-基]-3-氧代丙基}硫代）甲基]-2-[(8S)-8-（环己基甲基）-2-苯基-5,6-二氢咪唑[1,2-a]吡嗪-7（8H）-基]-2-氧代乙胺或其药学上可接受的盐，用作抗癌剂。
• G-PROTEIN INHIBITOR
  申请人：PREVOST Gregoire

  公开号：US20090137596A1

  公开（公告）日：2009-05-28

  A subject of the invention is a product comprising at least one Cdc25 phosphatase inhibitor in combination with at least one other anti-cancer agent for a therapeutic use which is simultaneous, separate or spread over time in the treatment of cancer. According to the invention, the other anti-cancer agent is preferably chosen from: analogues of DNA bases such as 5-fluorouracil; Type I and/or II topoisomerase inhibitors such as for example camptothecin and its analogues, doxorubicin or amsacrine; compounds interacting with the cell spindle such as for example paclitaxel (Taxol); compounds acting on the cytoskeleton such as vinblastine; inhibitors of the transduction of the signal passing through the heterotrimeric G proteins; prenyltransferase inhibitors, and in particular farnesyltransferase inhibitors; cyclin-dependent kinase (CDKs) inhibitors; alkylating agents such as cisplatin; antagonists of folic acid such as methotrexate; and inhibitors of the synthesis of DNA and cell division cell such as mitomycin C. A further subject of the invention is (1R)-1-[((2R)-2-amino-3-[(8S)-8-(cyclohexylmethyl)-2-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]-3-oxopropyl}dithio)methyl]-2-[(8S)-8-(cyclohexylmethyl)-2-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]-2-oxoethylamine, or a pharmaceutically acceptable salt thereof, useful as an anticancer agent.

  本发明的一个主题是一种产品，包括至少一种Cdc25磷酸酶抑制剂与至少一种其他抗癌剂的组合，用于治疗癌症的同时、分开或分散在时间上。根据本发明，其他抗癌剂优选从以下选择：DNA碱基类似物，如5-氟尿嘧啶；I型和/或II型拓扑异构酶抑制剂，如例如喜树碱及其类似物，多柔比星或阿米替林；与细胞纺锤相互作用的化合物，例如紫杉醇（紫杉醇）；作用于细胞骨架的化合物，例如长春新碱；通过异源三聚体G蛋白传递信号的抑制剂；戊烯基转移酶抑制剂，特别是法尼酰转移酶抑制剂；细胞周期蛋白依赖性激酶（CDKs）抑制剂；碱化剂，如顺铂；叶酸拮抗剂，如甲氨蝶呤；以及DNA合成和细胞分裂细胞的抑制剂，例如丝裂霉素C。本发明的另一个主题是(1R)-1-[((2R)-2-amino-3-[(8S)-8-(环己甲基)-2-苯基-5,6-二氢咪唑[1,2-a]吡嗪-7(8H)-基]-3-氧代丙基}二硫基)甲基]-2-[(8S)-8-(环己甲基)-2-苯基-5,6-二氢咪唑[1,2-a]吡嗪-7(8H)-基]-2-氧代乙基胺或其药学上可接受的盐，作为一种抗癌药物。
• ISOTOYPICALLY-LABELED BENZOTHIAZOLE COMPOUNDS AS IMAGING AGENTS FOR AMYLOIDOGENIC PROTEINS
  申请人：Klunk William E.

  公开号：US20090142269A1

  公开（公告）日：2009-06-04

  The present invention provides an isolated linezolid impurity, desfluoro linezolid, the preparation thereof and its use as a reference standard.

  本发明提供了一种分离的利奈唑酮杂质，去氟利奈唑酮，其制备方法及其用作参考标准的用途。