4-chloro-5-fluoro-6-methylpyrimidin-2-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-chloro-5-fluoro-6-methylpyrimidin-2-amine
• 英文别名: 2-amino-4-chloro-5-fluoro-6-methylpyrimidine
• 化学式: C₅H₅ClFN₃
• 分子量: 161.566
• InChiKey: JNCHETBCCQKKKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chloro-5-fluoro-6-methylpyrimidin-2-amine 、 正丁胺 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以76%的产率得到N4-butyl-5-fluoro-6-methylpyrimidine-2,4-diamine
  参考文献：
  名称：

  PYRIMIDINES AND USES THEREOF

  摘要：

  本文提供的各种示例是针对下述公式的化合物的：其中R1-R5在此处被定义，并且这些化合物的用途包括在其他方面抑制受试者的免疫反应。

  公开号：

  US20180215720A1
• 作为产物：
  描述：

  2-amino-5-fluoro-4-hydroxy-6-methylpyrimidine 在 三氯氧磷 作用下， 反应 3.0h， 以62%的产率得到4-chloro-5-fluoro-6-methylpyrimidin-2-amine
  参考文献：
  名称：

  PYRIMIDINES AND USES THEREOF

  摘要：

  本文提供的各种示例是针对下述公式的化合物的：其中R1-R5在此处被定义，并且这些化合物的用途包括在其他方面抑制受试者的免疫反应。

  公开号：

  US20180215720A1

文献信息

• [EN] SULPHAMOYLARYL DERIVATIVES AND USE THEREOF AS MEDICAMENTS FOR THE TREATMENT OF LIVER FIBROSIS<br/>[FR] DÉRIVÉS DE SULPHAMOYLARYLE ET LEUR UTILISATION EN TANT QUE MÉDICAMENTS POUR LE TRAITEMENT DE LA FIBROSE HÉPATIQUE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2018145620A1

  公开（公告）日：2018-08-16

  Potent 5-HT2B antagonist of Formula (A), including stereochemically isomeric forms, and salts, hydrates, solvates thereof and their use wherein R1 to R4 and Ar have the meaning as defined herein. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them, alone or in combination with other drugs, in fibrosis and/or cirrhosis prevention or therapy.

  强效的Formula（A）的5-HT2B拮抗剂，包括立体化异构形式，以及其盐、水合物、溶剂合物及其用途，其中R1至R4和Ar的含义如本文所定义。本发明还涉及制备所述化合物的方法，含有它们的药物组合物，单独或与其他药物联合在纤维化和/或肝硬化预防或治疗中的用途。
• Combination of a serotonin receptor antagonist with a histidine decarboxylase inhibitor as a medicament
  申请人：Biofrontera Pharmaceuticals AG

  公开号：EP1321169A1

  公开（公告）日：2003-06-25

  The present invention relates to the use of (S)-α-fluoromethylhistidine and esters and pharmaceutically acceptable salts thereof in combination with a serotonin receptor antagonist or a pharmaceutically acceptable salt thereof as a medicament and for the manufacture of a medicament for treatment of a disease state which can be alleviated by treatment with a serotonin receptor antagonist and/or a histamine receptor antagonist.

  本发明涉及使用(S)-α-氟甲基组氨酸及其酯和药学上可接受的盐与5-羟色胺受体拮抗剂或其药学上可接受的盐结合作为药物，并用于制造一种治疗可通过使用5-羟色胺受体拮抗剂和/或组胺受体拮抗剂进行缓解的疾病状态的药物。
• [EN] ARYL PYRIMIDINE DERIVATIVES<br/>[FR] DERIVES D'ARYL PYRIMIDINE
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：WO1997044326A1

  公开（公告）日：1997-11-27

  (EN) The present invention is directed to pyrimidine derivatives, and pharmaceutically acceptable salts and $i(N)-oxides thereof, which exhibit useful pharmacological properties, in particular use as selective 5HT2B-antagonists, their preparation, pharmaceutical compositions comprising them and their use in the treatment of various diseases, especially migraine. The invention is also directed to formulations and methods for treatment.(FR) Cette invention a trait à des dérivés d'aryl pyrimidine ainsi qu'à leurs sels et à leurs $i(N)-oxydes, acceptables d'un point de vue pharmaceutique. Ces substances, qui font montre d'utiles propriétés pharmacologiques, sont notamment efficaces comme antagonistes sélectifs de 5HT2B. L'invention a également trait à la préparation de ces substances, à des compositions pharmaceutiques les contenant, ainsi qu'à leur utilisation dans le traitement de troubles divers, de la migraine notamment. Elle concerne, de surcroît, des formulations et des méthodes thérapeutiques.

  本发明涉及嘧啶衍生物及其药学上可接受的盐和$i(N)$-氧化物，具有有用的药理学特性，特别是作为选择性5HT2B拮抗剂的用途，其制备，包含它们的制药组合物以及它们在治疗各种疾病，尤其是偏头痛方面的用途。本发明还涉及治疗方法和制剂。
• Sulphamoylaryl derivatives and use thereof as medicaments for the treatment of liver fibrosis
  申请人：Janssen Pharmaceutica NV

  公开号：US10654837B2

  公开（公告）日：2020-05-19

  Potent 5-HT2B antagonist of Formula (A), including stereochemically isomeric forms, and salts, hydrates, solvates thereof and their use wherein R1 to R4 and Ar have the meaning as defined herein. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them, alone or in combination with other drugs, in fibrosis and/or cirrhosis prevention or therapy.

  式(A)的强效5-HT2B拮抗剂，包括立体化学异构体形式，及其盐类、水合物、溶剂及其用途 其中R1至R4和Ar具有本文所定义的含义。本发明还涉及制备上述化合物的工艺、含有上述化合物的药物组合物，单独或与其他药物组合用于纤维化和/或肝硬化的预防或治疗。
• Human Toll-like Receptor (TLR) 8-Specific Agonistic Activity in Substituted Pyrimidine-2,4-diamines
  作者：Mallesh Beesu、Alex C. D. Salyer、Kathryn L. Trautman、Justin K. Hill、Sunil A. David

  DOI：10.1021/acs.jmedchem.6b00872

  日期：2016.9.8

  Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine profile favoring the generation of Type 1 helper T cells. A multiplexed high-throughput screen had led to the identification of N-4-butyl-5-iodo-6-methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed structure-activity relationship study of this chemotype was undertaken. A butyl substituent at N-4 was optimal, and replacement of the 5-iodo group with chloro, bromo, or fluoro groups led to losses in potency, as did the introduction of aromatic bulk. Drawing from our previous structure-based design, several 5-alkylamino derivatives were evaluated. Significant enhancement of potency was achieved in 5-(4-aminobutyl)-N-4-butyl-6-methylpyrimidine-2,4-diamine. This compound potently induced Th1-biasing IFN-gamma And IL-12 in human blood, but lower levels of the proinflammatory cytokines IL-1 beta, IL-6, and IL-8. These results suggest that the inflammatory and reactogenic propensities of this compound could be considerably more favorable than other TLR8 agonists under evaluation.