4-bromo-1-methyl-3-trifluoromethyl-5-pyrazolecarboxylic acid | 497833-05-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-bromo-1-methyl-3-trifluoromethyl-5-pyrazolecarboxylic acid
• 英文别名: 4-bromo-1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid；4-bromo-2-methyl-5-(trifluoromethyl)pyrazole-3-carboxylic acid
• CAS: 497833-05-3
• 化学式: C₆H₄BrF₃N₂O₂
• mdl: MFCD03419670
• 分子量: 273.009
• InChiKey: YAJINUFLHMNOQR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-bromo-1-methyl-3-trifluoromethyl-5-pyrazolecarboxylic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 4-bromo-1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-carbonyl chloride
  参考文献：
  名称：

  Potent Non-Nucleoside Inhibitors of the Measles Virus RNA-Dependent RNA Polymerase Complex

  摘要：

  Measles virus (MV) is one of the most infectious pathogens known. In spite of the existence of a vaccine, approximately 350000 deaths/year result from MV or associated complications. Antimeasles compounds Could conceivably diminish these statistics and provide a therapy that complements vaccine treatment. We recently described a high-throughput screening hit compound 1 (16677) against MV-infected cells with the capacity to eliminate viral reproduction at 250 nM by inhibiting the action of the virus's RNA-dependent RNA polymerase complex (RdRp). The compound, 1-methyl-3-(trifluoroi-nethyl)-N-[4-sulfonylphenyl]-1H-pyrazole-5-carboxamide, 1 carries a critical CF3 moiety on the 1,2-pyrazole ring. Elaborating on the preliminary structure-activity (SAR) study, the present work presents the synthesis and SAR of a much broader range of low nanomolar nonpeptidic MV inhibitors and speculates on the role of the CF3 functionality.

  DOI：

  10.1021/jm701239a
• 作为产物：
  描述：

  1-甲基-3-三氟甲基-1H-吡唑 在 正丁基锂 、 溴 、 铁粉 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 4.08h， 生成 4-bromo-1-methyl-3-trifluoromethyl-5-pyrazolecarboxylic acid
  参考文献：
  名称：

  可切换的反应性：三氟甲基取代吡唑的位点选择性功能化

  摘要：

  现代有机金属方法能够将简单的杂环起始材料区域灵活地转化为异构体和同系物家族。取决于试剂的选择，1-甲基-5-(三氟甲基)吡唑主要或仅在杂环的4-位或在氮连接的Me基团上经历去质子化和随后的羧化。类似地，1-苯基-5-(三氟甲基)吡唑和3-甲基-1-苯基-5-(三氟甲基)吡唑在杂环4-位被二异丙基氨基锂选择性攻击，在4-位被丁基锂和Ph 环的正交位置。相比之下，1-甲基-3-（三氟甲基）吡唑的金属化仅发生在 5 位，无论是有机金属碱还是金属氨化物碱。如果将溴引入杂环或芳基中，则其他位点可进行功能化。戒指。4-溴-1-甲基-5-（三氟甲基）吡唑、4-溴-1-甲基-3-（三氟甲基）吡唑、4-溴-1-甲基-5-（三氟甲基）吡唑和1-(2-溴苯基)-5-(三氟甲基)吡唑。[在 SciFinder (R) 上]

  DOI：

  10.1002/1099-0690(200209)2002:17<2913::aid-ejoc2913>3.0.co;2-d

文献信息

• Monoacylglycerol Lipase Modulators
  申请人：Janssen Pharmaceutica NV

  公开号：US20200102311A1

  公开（公告）日：2020-04-02

  Bridged compounds of Formula (I) and Formula (II), pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with MGL modulation, such as those associated with pain, psychiatric disorders, neurological disorders (including, but not limited to major depressive disorder, treatment resistant depression, anxious depression, bipolar disorder), cancers and eye conditions. wherein R 2 , R 3 R 4 , R 5 and R 6 are defined herein.

  桥接化合物，其结构式为(I)和(II)，包含它们的药物组合物，制造它们的方法，以及使用它们的方法，包括用于治疗与MGL调节相关的疾病状态、障碍和状况的方法，如与疼痛、精神障碍、神经障碍（包括但不限于重性抑郁障碍、难治性抑郁、焦虑性抑郁、双相情感障碍）、癌症和眼科疾病相关的方法。 其中R2、R3、R4、R5和R6的定义如下。
• Macrocyclic indole derivatives
  申请人：Bayer Aktiengesellschaft

  公开号：US10981932B2

  公开（公告）日：2021-04-20

  The present invention relates to macrocyclic indole derivatives of general formula (I): in which R1, R2, R3, R4, R5, R6, A and L are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for manufacturing pharmaceutical 2019 compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients.

  本发明涉及通式（I）的大环吲哚衍生物： 其中 R1、R2、R3、R4、R5、R6、A 和 L 如本文所定义；制备所述化合物的方法；用于制备所述化合物的中间体化合物；包含所述化合物的药物组合物和组合物；以及使用所述化合物制造用于治疗或预防疾病（尤其是过度增殖性疾病）的药物 2019 组合物，作为单独制剂或与其他活性成分组合使用。
• MACROCYCLIC INDOLE DERIVATIVES
  申请人：Bayer Aktiengesellschaft

  公开号：EP3458459A1

  公开（公告）日：2019-03-27
• MONOACYLGLYCEROL LIPASE MODULATORS
  申请人：Janssen Pharmaceutica N.V.

  公开号：EP3856179A1

  公开（公告）日：2021-08-04
• [EN] MACROCYCLIC INDOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'INDOLE MACROCYCLIQUES
  申请人：BAYER AG

  公开号：WO2017198341A1

  公开（公告）日：2017-11-23

  The present invention relates to macrocyclic indole derivatives of general formula (I) : (I), in which R1, R2, R3, R4, R5, R6, A and L are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients.