2-chloro-N-((tetrahydrofuran-2-yl)methyl)pyrimidin-4-amine | 880579-34-0

• 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: 2-chloro-N-((tetrahydrofuran-2-yl)methyl)pyrimidin-4-amine
• 英文别名: 2-chloro-N-(oxolan-2-ylmethyl)pyrimidin-4-amine
• CAS: 880579-34-0
• 化学式: C₉H₁₂ClN₃O
• mdl: MFCD06662494
• 分子量: 213.667
• InChiKey: ZHORVDFEESSQLC-UHFFFAOYSA-N

物化性质

• 沸点：
  416.2±15.0 °C(Predicted)
• 密度：
  1.310±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.555
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-N-((tetrahydrofuran-2-yl)methyl)pyrimidin-4-amine 在 氢氧化钾 、 三乙胺 作用下， 以 乙二醇 、 氯苯 为溶剂， 生成
  参考文献：
  名称：

  Characterization of mono- and diaminopyrimidine derivatives as novel, nonpeptide gonadotropin releasing hormone (GnRH) receptor antagonists

  摘要：

  A novel series of derivatives of mono- and diaminopyrimidines 1 potently displaced binding of a radiolabeled GnRH analogue to human and rat GnRH receptors. Analogues from these series competitively antagonized GnRH-stimulated increases in extracellular acidification in vitro and suppressed GnRH-mediated increases in circulating luteinizing hormone (LH) in castrated rats and testosterone in intact rats. These compounds or their analogues may be useful in treating sex hormone-dependent disease. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00756-4
• 作为产物：
  描述：

  2-四氢糠胺 、 2,4-二氯嘧啶 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 2-chloro-N-((tetrahydrofuran-2-yl)methyl)pyrimidin-4-amine 、 (4-Chloro-pyrimidin-2-yl)-(tetrahydro-furan-2-ylmethyl)-amine
  参考文献：
  名称：

  Characterization of mono- and diaminopyrimidine derivatives as novel, nonpeptide gonadotropin releasing hormone (GnRH) receptor antagonists

  摘要：

  A novel series of derivatives of mono- and diaminopyrimidines 1 potently displaced binding of a radiolabeled GnRH analogue to human and rat GnRH receptors. Analogues from these series competitively antagonized GnRH-stimulated increases in extracellular acidification in vitro and suppressed GnRH-mediated increases in circulating luteinizing hormone (LH) in castrated rats and testosterone in intact rats. These compounds or their analogues may be useful in treating sex hormone-dependent disease. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00756-4

文献信息

• Non-peptide GnRH agents, methods and intermediates for their preparation
  申请人：Pfizer Inc.

  公开号：US20040010033A1

  公开（公告）日：2004-01-15

  Non-peptide GnRH agents capable of inhibiting the effect of gonadotropin-releasing hormone are described. Such compounds and their pharmaceutically acceptable salts, multimers, prodrugs, and active metabolites are suitable for treating mammalian reproductive disorders and steroid hormone-dependent tumors as well as for regulating fertility, where suppression of gonadotropin release is indicated. Methods for synthesizing the compounds and intermediates useful in their preparation are also described.

  描述了能够抑制促性腺激素释放激素作用的非肽类GnRH药物。这些化合物及其药用盐、多聚体、前药和活性代谢物适用于治疗哺乳动物的生殖障碍和类固醇激素依赖性肿瘤，以及调节生育能力，其中指示抑制促性腺激素释放。还描述了合成这些化合物和在其制备中有用的中间体的方法。
• Development of Novel ACK1/TNK2 Inhibitors Using a Fragment-Based Approach
  作者：Harshani R. Lawrence、Kiran Mahajan、Yunting Luo、Daniel Zhang、Nathan Tindall、Miles Huseyin、Harsukh Gevariya、Sakib Kazi、Sevil Ozcan、Nupam P. Mahajan、Nicholas J. Lawrence

  DOI：10.1021/jm501929n

  日期：2015.3.26

  The tyrosine kinase ACK1, a critical signal transducer regulating survival of hormone-refractory cancers, is an important therapeutic target, for which there are no selective inhibitors in clinical trials to date. This work reports the discovery of novel and potent inhibitors for ACK1 tyrosine kinase (also known as TNK2) using an innovative fragment-based approach. Focused libraries were designed and synthesized by selecting fragments from reported ACK inhibitors to create hybrid structures in a mix and match process. The hybrid library was screened by enzyme-linked immunosorbent assay-based kinase inhibition and P-33 HotSpot assays. Systematic structure-activity relationship studies led to the identification of compound (R)-9b, which shows potent in vitro (IC50 = 56 nM, n = 3, P-33 HotSpot assay) and in vivo (IC50 < 2 mu M, human cancer cell lines) ACK1 inhibition. Both (R)-9b and (S)-9b were stable in human plasma and displayed a long half-life (t(1/2) > 6 h).