4-((3-chloro-4-(3,3,3-trifluoro-2-hydroxy-2-methylpropanamido)phenyl)thio)N,N-dimethylbenzamide | 1360607-89-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-((3-chloro-4-(3,3,3-trifluoro-2-hydroxy-2-methylpropanamido)phenyl)thio)N,N-dimethylbenzamide
• 英文别名: 4-[3-chloro-4-[[(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl]amino]phenyl]sulfanyl-N,N-dimethylbenzamide
• CAS: 1360607-89-1
• 化学式: C₁₉H₁₈ClF₃N₂O₃S
• 分子量: 446.878
• InChiKey: GBGDOJBGOGWZKH-GOSISDBHSA-N

物化性质

• 沸点：
  649.1±55.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  94.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-((3-chloro-4-(3,3,3-trifluoro-2-hydroxy-2-methylpropanamido)phenyl)thio)N,N-dimethylbenzamide 在 甲酸 、 双氧水 作用下， 生成 4-[[3-氯-4-[[(2R)-3,3,3-三氟-2-羟基-2-甲基-1-氧代丙基]氨基]苯基]磺酰基]-N,N-二甲基苯甲酰胺
  参考文献：
  名称：

  PDK抑制剂AZD7545的工艺开发和规模扩大

  摘要：

  简要比较了AZD7545的早期制造路线。详细报告了首选长期制造路线的工艺开发，并讨论了从最初的公斤级路线开始的变化。在每个阶段的讨论中都包含了中试工厂生产的放大经验。AZD7545整个开发过程中值得注意的方面涉及化学危害，机理，分析和杂质，本案例研究将重点关注这些方面。

  DOI：

  10.1021/op2003419
• 作为产物：
  描述：

  对氟苯腈 在 sodium sulfide 、 氯化亚砜 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.0h， 生成 4-((3-chloro-4-(3,3,3-trifluoro-2-hydroxy-2-methylpropanamido)phenyl)thio)N,N-dimethylbenzamide
  参考文献：
  名称：

  PDK抑制剂AZD7545的工艺开发和规模扩大

  摘要：

  简要比较了AZD7545的早期制造路线。详细报告了首选长期制造路线的工艺开发，并讨论了从最初的公斤级路线开始的变化。在每个阶段的讨论中都包含了中试工厂生产的放大经验。AZD7545整个开发过程中值得注意的方面涉及化学危害，机理，分析和杂质，本案例研究将重点关注这些方面。

  DOI：

  10.1021/op2003419

文献信息

• MODIFICATIONS OF THERAPEUTIC AGENTS FOR ENHANCED DELIVERY TO TARGET SITES
  申请人：Partikula LLC

  公开号：US20180028647A1

  公开（公告）日：2018-02-01

  Compositions of a modulator of cell metabolism, typically targeting cellular glycolysis, preferably with a targeting moiety, attached directly or indirectly to the inhibitor, or to a nanoparticle or other delivery vehicle thereof, and methods of use for treating cancer, proliferative disorders, neurodegenerative diseases, autoimmune disorders, or inflammatory diseases are provided. Pharmaceutical compositions including the targeted modulator and a pharmaceutically acceptable carrier are also provided. The pharmaceutical compositions can be administered to a subject in need thereof in an effective amount to reduce one or symptoms of the cancer, proliferative disorders, neurodegenerative diseases, autoimmune disorders, or inflammatory diseases alone or prior to or in conjunction with a further therapy such as radiotherapy.

  提供了细胞代谢调节剂的组成，通常以靶向细胞糖酵解为目标，最好带有一个靶向基团，直接或间接连接到抑制剂，或连接到纳米颗粒或其他递送载体上，并提供了用于治疗癌症、增生性疾病、神经退行性疾病、自身免疫性疾病或炎症性疾病的方法。还提供了包括靶向调节剂和药学上可接受的载体的药物组合物。这些药物组合物可以以有效剂量给需要的受试者使用，以减少癌症、增生性疾病、神经退行性疾病、自身免疫性疾病或炎症性疾病的症状之一或多个，独立使用或在放疗等进一步治疗之前或同时使用。
• Modifications of therapeutic agents for enhanced delivery to target sites
  申请人：Partikula LLC

  公开号：US10478492B2

  公开（公告）日：2019-11-19

  Compositions of a modulator of cell metabolism, typically targeting cellular glycolysis, preferably with a targeting moiety, attached directly or indirectly to the inhibitor, or to a nanoparticle or other delivery vehicle thereof, and methods of use for treating cancer, proliferative disorders, neurodegenerative diseases, autoimmune disorders, or inflammatory diseases are provided. Pharmaceutical compositions including the targeted modulator and a pharmaceutically acceptable carrier are also provided. The pharmaceutical compositions can be administered to a subject in need thereof in an effective amount to reduce one or symptoms of the cancer, proliferative disorders, neurodegenerative diseases, autoimmune disorders, or inflammatory diseases alone or prior to or in conjunction with a further therapy such as radiotherapy.

  本研究提供了细胞代谢调节剂的组合物，通常以细胞糖酵解为靶标，优选带有靶向分子，直接或间接连接到抑制剂上，或连接到其纳米颗粒或其他递送载体上，以及用于治疗癌症、增殖性疾病、神经退行性疾病、自身免疫性疾病或炎症性疾病的方法。还提供了包括靶向调节剂和药学上可接受的载体的药物组合物。这些药物组合物可以以有效量施用给有需要的受试者，以减少癌症、增殖性疾病、神经退行性疾病、自身免疫性疾病或炎症性疾病的一种或多种症状，可以单独施用，也可以在放疗等进一步治疗之前或与放疗一起施用。
• Kepner-Tregoe Decision Analysis as a Tool To Aid Route Selection. Part 2. Application to AZD7545, a PDK Inhibitor
  作者：Jonathan D. Moseley、David Brown、Catherine R. Firkin、Shelley L. Jenkin、Bharti Patel、Evan W. Snape

  DOI：10.1021/op800033c

  日期：2008.11.21

  Kepner-Tregoe decision analysis was formally used as an aid to route selection, as outlined in the preceding paper. Over 40 paper routes were assessed for suitability for both immediate and longer term manufacture of AZD7545, a compound in the early stages of development. Eight routes were then investigated in fall in the laboratory, and a further four in part, over a period of 3-4 months. From this exercise, the preferred long-term manufacturing route was identified before the first pilot scale manufacture had been completed. This route selection exercise worked well in this case where a large number of potential routes had to be considered using limited resources. It was also an effective means of bringing some long-term manufacturing issues to the fore at an early stage in development.