4-[4-cyano-3-(trifluoromethyl)-phenylcarbamoylamino]-N-methyl-2-fluorobenzamide | 1351185-73-3

• 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-[4-cyano-3-(trifluoromethyl)-phenylcarbamoylamino]-N-methyl-2-fluorobenzamide
• 英文别名: N-(3-trifluoromethyl-4-cyanophenyl)-N-(3-fluoro-4-carboxamidophenyl)urea；4-[[4-cyano-3-(trifluoromethyl)phenyl]carbamoylamino]-2-fluoro-N-methylbenzamide
• CAS: 1351185-73-3
• 化学式: C₁₇H₁₂F₄N₄O₂
• 分子量: 380.301
• InChiKey: VEZULCRYQHRKCB-UHFFFAOYSA-N

物化性质

• 沸点：
  422.8±45.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  94
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[4-cyano-3-(trifluoromethyl)-phenylcarbamoylamino]-N-methyl-2-fluorobenzamide 在 Lloyd's reagent 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以72.3%的产率得到4-{3-[4-cyano-3-(trifluoromethyl)phenyl]thioureido}-2-fluoro-N-methylbenzamide
  参考文献：
  名称：

  抗前列腺癌药物恩杂鲁胺的合成方法

  摘要：

  本发明公开了抗前列腺癌药物恩杂鲁胺的一种合成新方法。本发明属于制药合成工艺技术领域，具体是涉及一种合成恩杂鲁胺的新工艺。已知的恩杂鲁胺合成方法中，大多涉及使用剧毒、恶臭的硫光气以及剧毒的氰基丙酮，工业化难度较大。本发明通过使用无毒无害的劳氏试剂，将关键母核的羰基硫代，从而有效地规避了硫光气与氰基丙酮。同时该路线反应条件温和，收率较高，因此具有很强的工业化前景。

  公开号：

  CN104844521B
• 作为产物：
  描述：

  4-氨基-2-氟-n-甲基苯甲酰胺 、 4-氨基-2-三氟甲基苯甲腈 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 8.0h， 以88.1%的产率得到4-[4-cyano-3-(trifluoromethyl)-phenylcarbamoylamino]-N-methyl-2-fluorobenzamide
  参考文献：
  名称：

  抗前列腺癌药物恩杂鲁胺的合成方法

  摘要：

  本发明公开了抗前列腺癌药物恩杂鲁胺的一种合成新方法。本发明属于制药合成工艺技术领域，具体是涉及一种合成恩杂鲁胺的新工艺。已知的恩杂鲁胺合成方法中，大多涉及使用剧毒、恶臭的硫光气以及剧毒的氰基丙酮，工业化难度较大。本发明通过使用无毒无害的劳氏试剂，将关键母核的羰基硫代，从而有效地规避了硫光气与氰基丙酮。同时该路线反应条件温和，收率较高，因此具有很强的工业化前景。

  公开号：

  CN104844521B

文献信息

• CYCLIC N,N'-DIARYLTHIOUREAS AND N,N'-DIARYLUREAS - ANDROGEN RECEPTOR ANTAGONISTS, ANTICANCER AGENT, METHOD FOR PREPARATION AND USE THEREOF
  申请人：Ivachtchenko Alexandre Vasilievich

  公开号：US20130116269A1

  公开（公告）日：2013-05-09

  The present invention relates to novel cyclic N,N′-diarylureas and N,N′-diarylthioureas—androgen receptor antagonists, anti-cancer agent, pharmaceutical composition, medicament, and method for treatment of cancerous diseases, among them prostate cancer. Cyclic N,N′-diarylthioureas or N,N′-diarylureas of the general formula 1, their optical (R)- and (S)-isomers and pharmaceutically acceptable salts thereof exhibiting properties of androgen receptor antagonists have been proposed, wherein: X represents oxygen or sulfur; m=0 or 1; R1 represents C 1 -C 3 alkyl; R2 and R3 represent hydrogen; or R2 and R3 together with C-atom they are attached to form C═O group; R4 and R5 represent hydrogen; or R4 represents hydrogen, R5 represents methyl; or R4 represents methyl, R5 represents CH 2 R6 group in which R6 represents C 1 -C 3 alkoxycarbonyl, carboxyl, hydroxyl group optionally substituted with methyl or benzyl; or R4 and R5 together with C-atom they are attached to form 5- or 6-membered heterocycle comprising at least one oxygen atom or nitrogen atom optionally substituted with methyl; or R4 and R5 together with C-atom they are attached to form NH group.

  本发明涉及新颖的环状N,N′-二芳基脲和N,N′-二芳基硫脲—雄激素受体拮抗剂、抗癌剂、药物组合物、药物以及治疗癌症性疾病的方法，其中包括前列腺癌。已经提出了一般式1的环状N,N′-二芳基硫脲或N,N′-二芳基脲，它们的光学异构体(R)-和(S)-以及其药用盐具有雄激素受体拮抗剂的性质，其中：X代表氧或硫；m=0或1；R1代表C1-C3烷基；R2和R3代表氢；或R2和R3与它们连接的C原子一起形成C═O基团；R4和R5代表氢；或R4代表氢，R5代表甲基；或R4代表甲基，R5代表CH2R6基团，其中R6代表C1-C3烷氧羰基、羧基、羟基，可选择地被甲基或苄基取代；或R4和R5与C原子一起形成至少含有一个氧原子或氮原子的5-或6元杂环；或R4和R5与C原子一起形成NH基团。
• AN IMPROVED PROCESS FOR THE PREPARATION OF ENZALUTAMIDE
  申请人：Laurus Labs Private Limited

  公开号：US20170313662A1

  公开（公告）日：2017-11-02

  The present invention relates to an improved process for the preparation of enzalutamide by conventional synthesis, which avoids utilization of microwave irradiation and noxious reagents. The present invention also relates to an improved process for preparation of 4-isothiocyanato-2-(trifluoromethyl) benzonitrile, which is an intermediate in the synthesis of Enzalutamide.

  本发明涉及一种改进的常规合成制备恩扎鲁胺的方法，避免使用微波辐射和有害试剂。本发明还涉及一种改进的制备4-异硫氰酸基-2-(三氟甲基)苯甲腈的方法，该方法是制备恩扎鲁胺的中间体。
• CYCLIC N,N'-DIARYLTHIOUREA - ANDROGEN RECEPTOR ANTAGONIST, ANTI BREAST CANCER COMPOSITION AND USE THEREOF
  申请人：IVACHTCHENKO Alexandre Vasilievich

  公开号：US20130252992A1

  公开（公告）日：2013-09-26

  The present invention relates to novel cyclic N,N′-diarylurea-androgen receptor antagonist, anti-cancer agent, pharmaceutical composition, medicament, and method for treatment of breast cancer disease. Cyclic N,N′-diarylthioureas or N,N′-diarylureas of the general formula 1, their optical (R)- and (S)-isomers and pharmaceutically acceptable salts thereof exhibiting properties of androgen receptor antagonists have been proposed, wherein: R1 represents C 1 -C 3 alkyl; R4 and R5 represent hydrogen; or R4 represents hydrogen, R5 represents methyl; or R4 represents methyl, R5 represents CH 2 R6 group in which R6 is C 1 -C 3 alkoxycarbonyl, carboxyl, hydroxyl group optionally substituted with methyl or benzyl; or R4 and R5 together with the carbon atom they are attached to form 5- or 6-membered saturated heterocycle including at least one oxygen atom or nitrogen atom optionally substituted with methyl.

  本发明涉及一种新型的环状N,N′-二芳基脲-雄激素受体拮抗剂、抗癌剂、制药组合物、药物以及治疗乳腺癌疾病的方法。已经提出了一种具有雄激素受体拮抗剂性质的通式1的环状N,N′-二芳基硫脲或N,N′-二芳基脲，它们的光学异构体(R)-和(S)-异构体以及其药学上可接受的盐，其中：R1代表C1-C3烷基；R4和R5代表氢；或R4代表氢，R5代表甲基；或R4代表甲基，R5代表CH2R6基团，其中R6是C1-C3烷氧基羰基、羧基、羟基，可选地取代甲基或苄基；或R4和R5与它们所连接的碳原子一起形成5-或6-成员饱和杂环，包括至少一个氧原子或氮原子，可选地取代甲基。
• Cyclic N,N′-diarylthiourea—androgen receptor antagonist, anti breast cancer composition and use thereof
  申请人：Ivachtchenko Alexandre Vasilievich

  公开号：US09085539B2

  公开（公告）日：2015-07-21

  The present invention relates to novel cyclic N,N′-diarylurea—androgen receptor antagonist, anti-cancer agent, pharmaceutical composition, medicament, and method for treatment of breast cancer disease. Cyclic N,N′-diarylthioureas or N,N′-diarylureas of the general formula 1, their optical (R)- and (S)-isomers and pharmaceutically acceptable salts thereof exhibiting properties of androgen receptor antagonists have been proposed, wherein: R1 represents C1-C3 alkyl; R4 and R5 represent hydrogen; or R4 represents hydrogen, R5 represents methyl; or R4 represents methyl, R5 represents CH2R6 group in which R6 is C1-C3 alkoxycarbonyl, carboxyl, hydroxyl group optionally substituted with methyl or benzyl; or R4 and R5 together with the carbon atom they are attached to form 5- or 6-membered saturated heterocycle including at least one oxygen atom or nitrogen atom optionally substituted with methyl.

  本发明涉及一种新型的环状N,N'-二芳基脲-雄激素受体拮抗剂、抗癌剂、药物组合物、药物以及治疗乳腺癌疾病的方法。提出了一种具有雄激素受体拮抗剂性质的一般式1的环状N,N'-二芳基硫脲或N,N'-二芳基脲及其光学异构体(R)-和(S)-异构体以及其药学上可接受的盐，其中：R1代表C1-C3烷基；R4和R5代表氢；或R4代表氢，R5代表甲基；或R4代表甲基，R5代表CH2R6基团，其中R6是C1-C3烷氧羰基，羧基，羟基，可选地被甲基或苄基取代；或R4和R5与它们所附着的碳原子一起形成5-或6-成员饱和杂环，其中包括至少一个氧原子或氮原子，可选地被甲基取代。
• CYCLIC N,N'-DIARYLTHIOUREAS AND N,N'-DIARYLUREAS AS ANDROGEN RECEPTOR ANTAGONISTS, ANTI-CANCER AGENT, METHOD FOR PRODUCING AND USING SAME
  申请人：Ivachtchenko, Alexandre Vasilievich

  公开号：EP2597086A1

  公开（公告）日：2013-05-29

  The present invention relates to novel cyclic N,N'-diarylureas and N,N'-diarylthioureas - androgen receptor antagonists, anti-cancer agent, pharmaceutical composition, medicament, and method for treatment of cancerous diseases, among them prostate cancer. Cyclic N,N'-diarylthioureas or N,N'-diarylureas of the general formula 1, their optical (R)- and (S)- isomers and pharmaceutically acceptable salts thereof exhibiting properties of androgen receptor antagonists have been proposed, wherein: X represents oxygen or sulfur; m = 0 or 1; R1 represents C1-C3alkyl; R2 and R3 represent hydrogen; or R2 and R3 together with C-atom they are attached to form C = O group; R4 and R5 represent hydrogen; or R4 represents hydrogen, R5 represents methyl; or R4 represents methyl, R5 represents CH2R6 group in which R6 represents C1-C3 alkoxycarbonyl, carboxyl, hydroxyl group optionally substituted with methyl or benzyl; or R4 and R5 together with C-atom they are attached to form 5- or 6- membered heterocycle comprising at least one oxygen atom or nitrogen atom optionally substitutd with methyl; or R4 and R5 together with C-atom they are attached to form NH group.

  本发明涉及新型环状N,N'-二芳基脲类和N,N'-二芳基硫脲类--雄激素受体拮抗剂、抗癌剂、药物组合物、药物和治疗癌症疾病（其中包括前列腺癌）的方法。 已经提出了通式 1 的环状 N,N'-二芳基硫脲或 N,N'-二芳基硫脲、它们的光学 (R)- 和 (S)- 异构体及其药学上可接受的盐，它们具有雄激素受体拮抗剂的特性、 其中X 代表氧或硫； m = 0 或 1； R1 代表 C1-C3 烷基； R2和R3代表氢；或 R2 和 R3 与它们连接的 C 原子一起形成 C = O 基团； R4 和 R5 代表氢；或 R4 代表氢，R5 代表甲基；或 R4 代表甲基，R5 代表 CH2R6 基团，其中 R6 代表任选被甲基或苄基取代的 C1-C3 烷氧基羰基、羧基、羟基；或 R4 和 R5 与它们所连接的 C 原子一起形成 5 或 6 位杂环，该杂环包含至少一个任选被甲基取代的氧原子或氮原子；或 R4 和 R5 与它们连接的 C 原子形成 NH 基团。