BENZAMIDE,N-(4-甲基-3-硝基苯基)-3-(三氟甲基)- | 221876-21-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: BENZAMIDE,N-(4-甲基-3-硝基苯基)-3-(三氟甲基)-
• 英文名称: N-(4-methyl-3-nitrophenyl)-3-(trifluoromethyl)benzamide
• 英文别名: N-(3-nitro-4-methylphenyl)-3-(trifluoromethyl)benzamide
• CAS: 221876-21-7
• 化学式: C₁₅H₁₁F₃N₂O₃
• 分子量: 324.259
• InChiKey: MWVNSIAUXRLDHJ-UHFFFAOYSA-N

物化性质

• 沸点：
  339.0±42.0 °C(Predicted)
• 密度：
  1.410±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  BENZAMIDE,N-(4-甲基-3-硝基苯基)-3-(三氟甲基)- 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 45.5h， 生成 N-(4-methyl-3-(((4-(methylamino)-2-(methylthio)pyrimidin-5-yl)methyl)amino)phenyl)-3-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Discovery of 2-((3-Amino-4-methylphenyl)amino)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide (CHMFL-ABL-053) as a Potent, Selective, and Orally Available BCR-ABL/SRC/p38 Kinase Inhibitor for Chronic Myeloid Leukemia

  摘要：

  Starting from a dihydropyrimidopyrimidine core scaffold based compound 27 (GNF-7), we discovered a highly potent (ABL1: IC50 of 70 nM) and selective (S score (1) = 0.02) BCR-ABL inhibitor 18a (CHMFL-ABL-053). Compound 18a did not exhibit apparent inhibitory activity against c-KIT kinase, which is the common target of currently clinically used BCR-ABL inhibitors. Through significant suppression of the BCR-ABL autophosphorylation (EC50 about 100 nM) and downstream Mediators such as STATS, Crkl, and ERK's phosphorylation, 18a inhibited the proliferation of CML cell lines K562 (GI(50) = 14 nM), KU812 (GI(50) = 25 nM), and MEG-01 (GI(50) = 16 nM). A pharmacokinetic study revealed that 18a had over 4 h of half-life and 24% bioavailability in rats. A 50 mg/kg/day dosage treatment could almost completely suppress tumor progression in the K562 cells inoculated xenograft mouse model. As a potential useful drug candidate for CML, 18a is under extensive preclinical safety evaluation now.

  DOI：

  10.1021/acs.jmedchem.5b01618
• 作为产物：
  描述：

  3-(三氟甲基)苯甲酰氯 、 4-甲基-3-硝基苯胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以97%的产率得到BENZAMIDE,N-(4-甲基-3-硝基苯基)-3-(三氟甲基)-
  参考文献：
  名称：

  碳 11 标记的 5-(1-methyl-1H-pyrazol-4-yl)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)nicotinamide 作为 PET 示踪剂用于脑脊液成像的评价- 1R在大脑中的表达

  摘要：

  肿瘤微环境中肿瘤相关巨噬细胞和小胶质细胞的药理学靶向是治疗多形性胶质母细胞瘤的新治疗策略。因此，集落刺激因子-1 受体 (CSF-1R) 已被确定为可药物靶点。然而，迄今为止，还没有针对这些疗法的经过验证的伴随诊断标志物。开发 CSF-1R PET 示踪剂，一组六种化合物，基于最近报道的 CSF-1R 抑制剂 5-(1-methyl-1 H -pyrazol-4-yl)- N -(2-methyl-5-( 3-（三氟甲基）苯甲酰胺基）苯基）烟酰胺（化合物5）被设计、合成并在体外评估其效力和选择性。发现化合物5对 CSF-1R 的亲和力最高(IC 50 : 2.7 nM)。在轰击结束后的 40 分钟内，通过一氧化碳氨基羰基化以 2.0 ± 0.2% 的产率（衰减校正到合成开始）实现了 [ 11 C] 5 的后续放射合成。用[ 11 C] 5在大鼠脑切片上进行的体外放射自显影显示出高特异性结合

  DOI：

  10.1016/j.bmc.2021.116245

文献信息

• [EN] PYRAZOLOPYRIMIDINE DERIVATIVES, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL COMPOSITION FOR USE IN PREVENTING OR TREATING CANCER, AUTOIMMUNE DISEASE AND BRAIN DISEASE CONTAINING THE SAME AS AN ACTIVE INGREDIENT<br/>[FR] DÉRIVÉS DE PYRAZOLOPYRIMIDINE, LEUR PROCÉDÉ DE PRÉPARATION ET COMPOSITION PHARMACEUTIQUE POUR UTILISATION DANS LA PRÉVENTION OU LE TRAITEMENT DU CANCER, D'UNE MALADIE AUTO-IMMUNE ET D'UNE MALADIE DU CERVEAU CONTENANT CEUX-CI EN TANT QUE PRINCIPE ACTIF
  申请人：KOREA RES INST CHEMICAL TECH

  公开号：WO2018208132A1

  公开（公告）日：2018-11-15

  The present invention relates to a pyrazolopyrimidine derivative, a preparation method thereof and a pharmaceutical composition comprising the same as an active ingredient for the prevention or treatment of cancer, autoimmune disease and brain disease. The pyrazolopyrimidine derivative of the present invention exhibits excellent Bruton's tyrosine kinase inhibition activity, so that it can be effectively used as a pharmaceutical composition for the prevention or treatment of cancer, autoimmune disease and Parkinson's disease.

  本发明涉及一种吡唑并嘧啶衍生物，其制备方法以及包含该衍生物作为活性成分的药物组合物，用于预防或治疗癌症、自身免疫病和脑病。本发明的吡唑并嘧啶衍生物展现出卓越的布鲁顿酪氨酸激酶抑制活性，因此可以有效地用作预防或治疗癌症、自身免疫病和帕金森病的药物组合物。
• [EN] COMPOUNDS FOR USE IN INHIBITING HIV CAPSID ASSEMBLY<br/>[FR] COMPOSÉS À UTILISER POUR INHIBER L'ASSEMBLAGE DE CAPSIDE DU VIH
  申请人：RUPRECHT KARLS UNIVERSITÄT HEIDELBERG

  公开号：WO2014128213A1

  公开（公告）日：2014-08-28

  The present invention relates a compound or a pharmaceutically acceptable salt or solvate thereof for use in inhibiting HIV capsid assembly, wherein the compound is a pyrimidine being at least substituted in two positions, preferably in 2 and 4 position or in 4 and 6 position, more preferably in 2 and 4 position.

  本发明涉及一种化合物或其药用可接受的盐或溶剂，用于抑制HIV衣壳组装，其中该化合物是一种嘧啶，在至少两个位置上被取代，最好在2和4位置或在4和6位置，更好地在2和4位置。
• Bezamide derivatives for the treatment of diseases mediated by cytokines
  申请人：AstraZeneca AB

  公开号：US06579872B1

  公开（公告）日：2003-06-17

  The invention concerns the use of amide derivatives of formula (I) wherein: R1 and R2 are substituents such as hydroxy, C1-6alkoxy, mercapto, C1-6alkylthio, amino, C1-6alkylamino and di-(C1-6alkyl)amino; m and p are independently 0-3; R3 is C1-4alkyl; q is 0-4; and R4 is aryl or cycloalkyl; or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for use in the treatment of diseases or medical conditions mediated by cytokines.

  本发明涉及使用式（I）的酰胺衍生物，其中：R1和R2是取代基，例如羟基，C1-6烷氧基，巯基，C1-6烷基硫基，氨基，C1-6烷基氨基和二（C1-6烷基）氨基；m和p独立地为0-3；R3为C1-4烷基；q为0-4；而R4为芳基或环烷基；或其药学上可接受的盐制剂，用于制造治疗因细胞因子介导的疾病或医疗条件的药物。
• Amide derivatives useful as inhibitors of the production of cytokines
  申请人：AstraZeneca AB

  公开号：US06432949B1

  公开（公告）日：2002-08-13

  The invention concerns amide derivatives of formula (I) wherein R3 is (1-6C)alkyl or halogeno; Q1 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 R2 is a substituent such as hydroxy and halogeno; q is 0-4; and Q2 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.

  该发明涉及式(I)的酰胺衍生物，其中R3为(1-6C)烷基或卤素；Q1为杂环芳基，可选地取代为1、2、3或4个取代基，如羟基、卤素、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为羟基和卤素等取代基；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。
• Amide derivatives for the treatment of diseases mediated by cytokines
  申请人：Zeneca Limited

  公开号：US06498274B1

  公开（公告）日：2002-12-24

  The invention concerns the use of amide derivatives of formula (I) wherein: R1 and R2 are substituents such as hydroxy, C1-6alkoxy, mercapto, C1-6alkylthio, amino, C1-6alkylamino and di-(C1-6alkyl)amino; m and p are independently 0-3R3 is C1-4alkyl; q is 0-4; and R4 is aryl or cycloalkyl; or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for use in the treatment of diseases or medical conditions mediated by cytokines

  该发明涉及使用式(I)的酰胺衍生物，其中：R1和R2是取代基，如羟基、C1-6烷氧基、巯基、C1-6烷基硫基、氨基、C1-6烷基氨基和二-(C1-6烷基)氨基；m和p独立地为0-3；R3为C1-4烷基；q为0-4；R4为芳基或环烷基；或其在制备用于治疗由细胞因子介导的疾病或医疗状况的药物中的药用盐。