3-morpholino-5-(trifluoromethyl)benzoyl chloride | 250682-09-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 3-morpholino-5-(trifluoromethyl)benzoyl chloride
• 英文别名: 3-Morpholino-5-trifluoromethylbenzoyl chloride；3-morpholin-4-yl-5-(trifluoromethyl)benzoyl chloride
• CAS: 250682-09-8
• 化学式: C₁₂H₁₁ClF₃NO₂
• 分子量: 293.673
• InChiKey: WHQMQXJFEIEOGQ-UHFFFAOYSA-N

物化性质

• 沸点：
  382.4±42.0 °C(Predicted)
• 密度：
  1.380±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-morpholino-5-(trifluoromethyl)benzoyl chloride 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 N-(3-amino-4-methylphenyl)-3-morpholino-5-trifluoromethylbenzamide
  参考文献：
  名称：

  A novel series of p38 MAP kinase inhibitors for the potential treatment of rheumatoid arthritis

  摘要：

  A novel p38 MAP kinase inhibitor structural class was discovered through selectivity screening. The rational analogue design, synthesis and structure-activity relationship of this series of bisamide inhibitors is reported. The inhibition in vitro of human p38alpha enzyme activity and lipopolysaccharide-induced tumour necrosis factor-alpha release is described for the series. The activity in vivo and pharmacokinetic properties are exemplified for the more potent analogues. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.006
• 作为产物：
  描述：

  3-吗啉-5-(三氟甲基)苯甲酸 在 氯化亚砜 作用下， 生成 3-morpholino-5-(trifluoromethyl)benzoyl chloride
  参考文献：
  名称：

  [EN] ISOXAZOLE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF AND USE THEREOF
  [FR] DÉRIVÉ D'ISOXAZOLE OU SEL PHARMACEUTIQUEMENT ACCEPTABLE DE CELUI-CI ET LEUR UTILISATION
  [KO] 이속사졸 유도체 또는 이의 약학적으로 허용가능한 염 및 이의 용도

  摘要：

  本发明涉及用于预防或治疗 CSF-1R 相关疾病的组合物，该组合物包含异噁唑衍生物或其药学上可接受的盐以及作为活性成分的所述衍生物，其中本发明的异噁唑衍生物可抑制 CSF-1R，并可用于预防或治疗 CSF-1R 相关疾病，如神经退行性脑病。

  公开号：

  WO2023096304A1

文献信息

• Benzamide derivatives and their use as cytokine inhibitors
  申请人：Astra Zeneca AB

  公开号：US06455520B1

  公开（公告）日：2002-09-24

  The invention concerns amide derivatives of formula (I) wherein R3 is (1-6C)alkyl or halogeno; m is 0-3, p is 0-2 and q is 0-4; each of R1 and R2 is a group such as hydroxy, halogeno, trifluoromethyl and cyano; R4 is a basic group such as amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, di-[(1-6C)alkyl]amino-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(2-6C)alkoxy, heteroaryl, heteroaryloxy, heteroaryl-(1-6C)alkoxy, heterocyclyl, heterocyclyloxy and heterocyclyl-(1-6C)alkoxy; and Q2 is a group such as heteroaryl, heteroaryloxy or heteroaryl-(1-6C)alkoxy which is optionally substituted; or pharmaceutically-acceptable salts or in-vivo-cleavable esters thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical conditions mediated by cytokines.

  该发明涉及式(I)的酰胺衍生物 其中R3是(1-6C)烷基或卤素；m为0-3，p为0-2，q为0-4；R1和R2中的每一个是羟基、卤素、三氟甲基和氰基等基团；R4是氨基、(1-6C)烷基氨基、二-[（1-6C）烷基]氨基、二-[（1-6C）烷基]氨基-(1-6C)烷基、二-[（1-6C）烷基]氨基-(2-6C)氧烷基、杂环芳基、杂环芳氧基、杂环芳基-(1-6C)氧烷基、杂环烷基、杂环氧基和杂环烷基-(1-6C)氧烷基；Q2是杂环芳基、杂环芳氧基或杂环芳基-(1-6C)氧烷基等基团，可选择性地被取代；或其药学上可接受的盐或体内可水解酯；它们的制备方法、含有它们的药物组合物以及它们在治疗由细胞因子介导的疾病或医疗状况中的用途。
• Discovery of 5-methyl-<i>N</i>-(2-arylquinazolin-7-yl)isoxazole-4-carboxamide analogues as highly selective FLT3 inhibitors
  作者：Daseul Im、Hyungwoo Moon、Jinwoong Kim、Youri Oh、Miyoung Jang、Jung-Mi Hah

  DOI：10.1080/14756366.2020.1758689

  日期：2020.1.1

  conformational rigidification of a previous type II FMS inhibitor. Most of quinazoline analogues displayed activity against FLT3 and FLT3-ITD. Compound 7d, 5-methyl-N-(2-(3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl)quinazolin-7-yl)isoxazole-4-carboxamide, exhibited the most potent inhibitory activity against FLT3 (IC50= 106 nM) with excellent selectivity profiles over 36 other protein kinases including

  基于先前的II型FMS抑制剂的构象刚性，设计和合成了一系列具有喹唑啉核心的4-芳基氨基5-甲基异恶唑衍生物。大多数喹唑啉类似物表现出针对FLT3和FLT3-ITD的活性。化合物7d 5-甲基-N-（2-（3-（4-甲基哌嗪-1-基）-5-（三氟甲基）苯基）喹唑啉-7-基）异恶唑-4-羧酰胺表现出最强的抑制活性针对FLT3（IC50 = 106 nM）的抗性，具有优于其他36种蛋白激酶（包括cKit和FMS激酶）的选择性。化合物7d在FLT-ITD中也具有活性，IC50值为301 nM，其他FLT3突变体也显示出作为AML治疗药物的潜力。
• Amide derivatives
  申请人：Brown S. Dearg

  公开号：US20050245551A1

  公开（公告）日：2005-11-03

  The invention concerns amide derivatives of Formula (Ia) wherein X is —NHCO— or —CONH—; m is 0-3; R 1 is a group such as hydroxy, halogeno, trifluoromethyl, cyano, mercapto, nitro, amino, carboxy and carbamoyl; n is 0-2; R 2 is a group such as hydroxy, halogeno, trifluoromethyl, cyano, mercapto, nitro, amino and carboxy; R 3 is hydrogen, halogeno, (1-6C)alkyl or (1-6C)alkoxy; q is 0-4; and Q is a group such as aryl, aryloxy, aryl-(1-6C)alkoxy, arylamino and N -(1-6C)alkyl-arylamino; or pharmaceutically-acceptable salts or in-vivo-cleavable esters thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical conditions mediated by cytokines.

  本发明涉及式(Ia)的酰胺衍生物，其中X为—NHCO—或—CONH—；m为0-3；R1为羟基、卤代、三氟甲基、氰基、巯基、硝基、氨基、羧基和氨基甲酰基等基团；n为0-2；R2为羟基、卤代、三氟甲基、氰基、巯基、硝基、氨基和羧基等基团；R3为氢、卤代、(1-6C)烷基或(1-6C)烷氧基；q为0-4；Q为芳基、芳氧基、芳基-(1-6C)烷氧基、芳基氨基和N-(1-6C)烷基-芳基氨基等基团；或其药学上可接受的盐或体内可降解的酯；制备它们的方法、含有它们的制药组合物以及它们在治疗细胞因子介导的疾病或医疗状况中的用途。
• Benzamide derivatives for the treatment of diseases mediated by cytokines
  申请人：ASTRAZENECA AB

  公开号：US20030212068A1

  公开（公告）日：2003-11-13

  1 The invention concerns amide derivatives of Formula (I), wherein R 3 is (1-6C)alkyl or halogeno; m is 1-3 and R 1 is selected from substituents such as: (A) hydroxy, halogeno, (1-6C)alkyl, (1-6C)alkoxy, aryl, heteroaryl and heterocyclyl; and (B) di-[(1-6C)alkyl]amino-(1-6C)alkyl, (1-6C)alkoxy-(2-6C)alkoxy, di-[(1-6C)alkyl]amino-(2-6C)alkoxy, aryloxy, heteroaryloxy, heteroaryl-(1-6C)alkoxy, heterocyclyloxy and heterocyclyl-(1-6C)alkoxy; p is 0-2 and R 2 is a substituent such as hydroxy and halogeno; q is 0-4; and R 4 is aryl or cycloalkyl which bears 1-3 substituents such as: (C) hydrogen, hydroxy, halogeno and heterocyclyl; and (D) heteroaryl-(1-6C)alkoxy and heterocyclyl-(1-6C)alkoxy, provided that a substituent on R 4 is selected from paragraph (C) only if at least one R 1 group is selected from paragraph (B); processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical conditions mediated by cytokines.

  该发明涉及式(I)的酰胺衍生物，其中R3是(1-6C)烷基或卤素；m为1-3，R1被选择为以下取代基之一：(A)羟基、卤素、(1-6C)烷基、(1-6C)烷氧基、芳基、杂芳基和杂环基；和(B)二-[(1-6C)烷基]氨基-(1-6C)烷基、(1-6C)烷氧基-(2-6C)烷氧基、二-[(1-6C)烷基]氨基-(2-6C)烷氧基、芳氧基、杂芳氧基、杂芳基-(1-6C)烷氧基、杂环氧基和杂环基-(1-6C)烷氧基；p为0-2，R2是羟基和卤素等取代基；q为0-4；R4是芳基或环烷基，其带有1-3个取代基，例如：(C)氢、羟基、卤素和杂环基；和(D)杂芳基-(1-6C)烷氧基和杂环基-(1-6C)烷氧基，但仅当至少一个R1基团选择自段(B)时，才从段(C)中选择R4上的取代基；制备它们的方法，含有它们的制药组合物，以及它们在治疗由细胞因子介导的疾病或医疗状况中的应用。
• Amide derivatives useful as inhibitors of the production of cytokines
  申请人：ASTRAZENECA AB

  公开号：US20030105142A1

  公开（公告）日：2003-06-05

  The invention concerns amide derivatives of formula (I) wherein R 3 is (1-6C)alkyl or halogeno; Q 1 is heteroaryl which is optionally substituted with 1, 2, 3, or 4 substituents such as hydroxy, halogeno, trifluoromethyl, (1-6C)alkyl, (1-6C)alkoxy, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, hydroxy-(2-6C)alkoxy, amino-(2-6C)alkylamino, N-(1-6C)alkyl-(1-6C)alkylamino-(2-6C)alkylamino, aryl, heteroaryl and heterocyclyl; p is 0-2 and R 2 is a substituent such as hydroxy and halogeno; q is 0-4; and Q 2 includes optionally substituted aryl, cycloalkyl, heteroaryl and heterocyclyl; or pharmaceutically-acceptable salts or in vivo-cleavable esters thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical conditions mediated by cytokines.

  本发明涉及式（I）的酰胺衍生物，其中R3是（1-6C）烷基或卤素基；Q1是杂环芳基，可以用1、2、3或4个取代基，例如羟基、卤素基、三氟甲基、（1-6C）烷基、（1-6C）烷氧基、羟基-（1-6C）烷基、（1-6C）烷氧基-（1-6C）烷基、羟基-（2-6C）烷氧基、氨基-（2-6C）烷基氨基、N-（1-6C）烷基-（1-6C）烷基氨基-（2-6C）烷基氨基、芳基、杂环芳基和杂环烷基；p为0-2，R2是羟基和卤素基等取代基；q为0-4；Q2包括可选取代的芳基、环烷基、杂环芳基和杂环烷基；或其药学上可接受的盐或体内可水解的酯；其制备方法、包含它们的制药组合物以及它们在治疗细胞因子介导的疾病或医学状况中的用途。