4,6-二甲基-2-(三氟甲基)嘧啶-5-羧酸 | 544704-08-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4,6-二甲基-2-(三氟甲基)嘧啶-5-羧酸
• 英文名称: 4,6-dimethyl-2-trifluoromethyl-pyrimidine-5-carboxylic acid
• 英文别名: 4,6-Dimethyl-2-(trifluoromethyl)pyrimidine-5-carboxylic acid
• CAS: 544704-08-7
• 化学式: C₈H₇F₃N₂O₂
• 分子量: 220.151
• InChiKey: VYPLQBIHGYKXRS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  (S)-5-butyl-9-(4-methylpiperidin-4-yl)-3-((tetrahydro-2H-pyran-4-yl)methyl)-1-oxa-3,9-diazaspiro[5.5]undecan-2-one 、 4,6-二甲基-2-(三氟甲基)嘧啶-5-羧酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-5-butyl-9-(1-(4,6-dimethyl-2-(trifluoromethyl)pyrimidine-5-carbonyl)-4-methylpiperidin-4-yl)-3-((tetrahydro-2H-pyran-4-yl)methyl)-1-oxa-3,9-diazaspiro[5.5]undecan-2-one
  参考文献：
  名称：

  Spiropiperidine CCR5 antagonists

  摘要：

  A novel series of CCR5 antagonists has been identified, utilizing leads from high-throughput screening which were further modified based on insights from competitor molecules. Lead optimization was pursued by balancing opposing trends of metabolic stability and potency. Selective and potent analogs with good pharmacokinetic properties were successfully developed. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.122
• 作为产物：
  描述：

  2-bromo-6-[(3-fluoro-4-methoxybenzoyl)amino]-4-methoxyphenyl-3-fluoro-4-methoxybenzoate 在 acidic solution 、 sodium ethanolate 作用下， 以 乙醇 为溶剂， 生成 4,6-二甲基-2-(三氟甲基)嘧啶-5-羧酸
  参考文献：
  名称：

  Piperazine-based CCR5 antagonists as HIV-1 inhibitors. III: synthesis, antiviral and pharmacokinetic profiles of symmetrical heteroaryl carboxamides

  摘要：

  The unsymmetrical nicotinamide-N-oxide moiety in compound I was replaced with symmetrical isonicotinamides as well as 4,6-dimethyl pyrimidine-5-carboxamides. Compound 16 from the latter set reduced the number of rotamers, improved potency of inhibiting UIV entry, slightly diminished the affinity for the muscarine receptors and showed very good oral absorption. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00918-6

文献信息

• Piperazine derivatives useful as CCR5 antagonists
  申请人：Schering Corporation

  公开号：US06391865B1

  公开（公告）日：2002-05-21

  The use of CCR5 antagonists of the formula or a pharmaceutically acceptable salt thereof, wherein R is optionally substituted phenyl, pyridyl, thiophenyl or naphthyl; R1 is hydrogen or alkyl; R2 is substituted phenyl, substituted heteroaryl, naphthyl, fluorenyl, diphenylmethyl or optionally substituted phenyl- or heteroaryl-alkyl; R3 is hydrogen, alkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, or optionally substituted phenyl, phenylalkyl, naphthyl, naphthylalkyl, heteroaryl or heteroarylalkyl; R4, R5 and R7 are hydrogen or alkyl; R6 is hydrogen, alkyl or alkenyl; for the treatment of HIV, solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis is disclosed, as well as novel compounds, pharmaceutical compositions comprising them, and the combination of CCR5 antagonists of the invention in combination with antiviral agents useful in the treatment of HIV or agents useful in the treatment of inflammatory diseases.

  公开了使用CCR5拮抗剂的公式，其中 R是可选择的取代苯基，吡啶基，噻吩基或萘基; R1是氢或烷基; R2是取代苯基，取代杂环基，萘基，芴基，二苯甲基或可选择的取代苯基或杂环基烷基; R3是氢，烷基，烷氧基烷基，环烷基，环烷基烷基，或可选择的取代苯基，苯基烷基，萘基，萘基烷基，杂环基或杂环基烷基; R4，R5和R7是氢或烷基; R6是氢，烷基或烯基; 用于治疗HIV，固体器官移植排斥，移植物宿主病，关节炎，类风湿关节炎，炎症性肠病，特应性皮炎，牛皮癣，哮喘，过敏或多发性硬化症的方法，以及包含它们的新化合物，包含它们的药物组合物，以及CCR5拮抗剂与抗HIV治疗中有用的抗病毒剂或与治疗炎症性疾病中有用的药物的组合。
• Heterocylic antiviral compounds
  申请人：Rotstein David Mark

  公开号：US20080249087A1

  公开（公告）日：2008-10-09

  This invention relates to piperidine derivatives of formula I wherein R 1 , R 2 , R 3 and R 4 are as defined herein useful in the treatment of a variety of disorders, including those in which the modulation of CCR5 receptors is implicated. Disorders that may be treated or prevented by the present derivatives include HIV and genetically related retroviral infections (and the resulting acquired immune deficiency syndrome, AIDS), rheumatoid arthritis, solid organ transplant reject (graft vs. host disease), asthma and COPD.

  这项发明涉及式I的哌啶衍生物，其中R1、R2、R3和R4如本文所定义，在治疗各种疾病中有用，包括那些涉及CCR5受体调节的疾病。目前这些衍生物可以治疗或预防的疾病包括HIV和遗传相关的逆转录病毒感染（以及由此导致的获得性免疫缺陷综合症，艾滋病），类风湿性关节炎，固体器官移植排斥（移植物抗宿主病），哮喘和慢性阻塞性肺病（COPD）。
• Evaluation of secondary amide replacements in a series of CCR5 antagonists as a means to increase intrinsic membrane permeability. Part 1: Optimization of gem-disubstituted azacycles
  作者：Rémy C. Lemoine、Ann C. Petersen、Lina Setti、Jutta Wanner、Andreas Jekle、Gabrielle Heilek、André deRosier、Changhua Ji、Pamela Berry、David Rotstein

  DOI：10.1016/j.bmcl.2009.11.072

  日期：2010.1

  Replacement of a secondary amide with an N-acyl or N-sulfonyl gem-disubstituted azacyle in a series of CCR5 antagonists led to the identification of compounds with excellent in vitro HIV antiviral activity and increased intrinsic membrane permeability.

  在一系列CCR5拮抗剂中，用N-酰基或N-磺酰基的宝石二取代的氮杂取代仲酰胺导致鉴定出具有出色的体外HIV抗病毒活性和增加的固有膜通透性的化合物。
• Octahydro-pyrrolo[3,4-c]pyrrole CCR5 receptor antagonists
  申请人：Roche Palo Alto LLC

  公开号：US07625905B2

  公开（公告）日：2009-12-01

  Chemokine receptor antagonists, in particular, 3,7-diazabicyclo[3.3.0]octane compounds according to formula (I) wherein R1-R3 and Ar are as defined herein are antagonists of chemokine CCR5 receptors which are useful for treating or preventing an human immunodeficiency virus (HIV) infection, or treating AIDS or ARC. The invention further provides methods for treating diseases that are alleviated with CCR5 antagonists. The invention includes pharmaceutical compositions and methods of using the compounds for the treatment of these diseases. The invention further includes processes for the preparation of compounds according to formula I.

  化学因子受体拮抗剂，特别是根据公式（I）中定义的R1-R3和Ar的3,7-二氮杂双环[3.3.0]辛化合物，是化学因子CCR5受体的拮抗剂，用于治疗或预防人类免疫缺陷病毒（HIV）感染，或治疗艾滋病或ARC。本发明还提供了治疗使用CCR5拮抗剂缓解的疾病的方法。本发明包括制备公式I中化合物的药物组合物和使用这些化合物治疗这些疾病的方法。本发明还包括制备公式I中化合物的方法。
• Oximino-piperidino-piperidine-based CCR5 antagonists. Part 2: synthesis, SAR and biological evaluation of symmetrical heteroaryl carboxamides
  作者：Anandan Palani、Sherry Shapiro、John W. Clader、William J. Greenlee、Susan Vice、Stuart McCombie、Kathleen Cox、Julie Strizki、Bahige M. Baroudy

  DOI：10.1016/s0960-894x(02)01063-6

  日期：2003.2

  The synthesis, SAR and biological evaluation of symmetrical amide analogues of our clinical candidate SCH 351125 are described. A series of potent and orally bioavailable CCR5 antagonists containing symmetrical 2,6-dimethyl isonicotinamides and 2, 6-dimethyl pyrimidines amides were generated with enhanced affinity for the CCR5 receptor. (C) 2003 Elsevier Science Ltd. All rights reserved.