(R)-4-isopropyl-6-(3-methylaminopyrrolidin-1-yl)pyrimidin-2-ylamine | 1046447-88-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (R)-4-isopropyl-6-(3-methylaminopyrrolidin-1-yl)pyrimidin-2-ylamine
• 英文别名: 4-isopropyl-6-((3R)-3-(methylamino)pyrrolidin-1-yl)pyrimidin-2-amine；4-[(3R)-3-(methylamino)pyrrolidin-1-yl]-6-propan-2-ylpyrimidin-2-amine
• CAS: 1046447-88-4
• 化学式: C₁₂H₂₁N₅
• 分子量: 235.332
• InChiKey: MPMKEVCRBCBJMY-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  67.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基-4-异丙基-6-氯嘧啶 在 盐酸 、 甲酸 、 三乙胺 作用下， 以 乙醇 、 水 为溶剂， 反应 18.0h， 生成 (R)-4-isopropyl-6-(3-methylaminopyrrolidin-1-yl)pyrimidin-2-ylamine
  参考文献：
  名称：

  Discovery and SAR of 6-Alkyl-2,4-diaminopyrimidines as Histamine H₄ Receptor Antagonists

  摘要：

  This report discloses the discovery and SAR of a series of 6-alkyl-2-aminopyrimidine derived histamine H4 antagonists that led to the development of JNJ 39758979, which has been studied in phase II clinical trials in asthma and atopic dermatitis. Building on our SAR studies of saturated derivatives from the indole carboxamide series, typified by JNJ 7777120, and incorporating knowledge from the tricyclic pyrimidines led us to the 6-alkyl-2,4-diaminopyrimidine series. A focused medicinal chemistry effort delivered several 6-alkyl-2,4-diaminopyrimidines that behaved as antagonists at both the human and rodent H4 receptor. Further optimization led to a panel of antagonists that were profiled in animal models of inflammatory disease. On the basis of the preclinical profile and efficacy in several animal models, JNJ 39758979 was selected as a clinical candidate; however, further development was halted during phase II because of the observation of drug-induced agranulocytosis (DIAG) in two subjects.

  DOI：

  10.1021/jm401727m

文献信息

• 2-Aminopyrimidine modulators of the histamine H4 receptor
  申请人：Cai Hui

  公开号：US20080194577A1

  公开（公告）日：2008-08-14

  2-Aminopyrimidine compounds are described, which are useful as H 4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H 4 receptor activity, such as allergy, asthma, autoimmune diseases, and pruritis.

  描述了2-氨基嘧啶化合物，这些化合物可作为H4受体调节剂。这些化合物可用于制药组合物和治疗由H4受体活性介导的疾病状态、疾病和病况的方法，如过敏、哮喘、自身免疫疾病和瘙痒症。
• Selective Histamine H4 Receptor Antagonists for the Treatment of Vestibular Disorders
  申请人：Desmadryl Gilles

  公开号：US20120039913A1

  公开（公告）日：2012-02-16

  The invention relates to Histamine H4 receptor antagonists or inhibitors of Histamine H4 receptor gene expression for the treatment and/or the prevention of vestibular disorders.

  该发明涉及组胺H4受体拮抗剂或组胺H4受体基因表达抑制剂，用于治疗和/或预防前庭障碍。
• 2-AMINOPYRIMIDINE MODULATORS OF THE HISTAMINE H4 RECEPTOR
  申请人：Cai Hui

  公开号：US20110218338A1

  公开（公告）日：2011-09-08

  2-Aminopyrimidine compounds are described, which are useful as H 4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H 4 receptor activity, such as allergy, asthma, autoimmune diseases, and pruritus.

  本文描述了2-氨基嘧啶化合物，这些化合物可用作H4受体调节剂。这些化合物可用于制备药物组合物和治疗疾病状态、障碍和条件的方法，这些状态、障碍和条件是由H4受体活性介导的，例如过敏、哮喘、自身免疫性疾病和瘙痒症。
• 2-aminopyrimidine modulators of the histamine h4 receptor
  申请人：Janssen Pharmaceutica N.V.

  公开号：EP2599386A1

  公开（公告）日：2013-06-05

  2-Aminopyrimidine compounds are described, which are useful as H4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H4 receptor activity, such as allergy, asthma, autoimmune diseases, and pruritis.

  本文描述了可用作 H4 受体调节剂的 2-氨基嘧啶化合物。此类化合物可用于治疗由 H4 受体活性介导的疾病状态、紊乱和病症（如过敏、哮喘、自身免疫性疾病和瘙痒症）的药物组合物和方法中。
• SELECTIVE HISTAMINE H4 RECEPTOR ANTAGONISTS FOR THE TREATMENT OF VESTIBULAR DISORDERS
  申请人：INSERM (Institut National de la Santé et de la Recherche Médicale)

  公开号：EP3130376A1

  公开（公告）日：2017-02-15

  The invention relates to Histamine H4 receptor antagonists or inhibitors of Histamine H4 receptor gene expression for the treatment and/or the prevention of vestibular disorders.

  本发明涉及组胺 H4 受体拮抗剂或组胺 H4 受体基因表达抑制剂，用于治疗和/或预防前庭失调。