7-chloro-3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine | 900295-57-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 7-chloro-3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine
• CAS: 900295-57-0
• 化学式: C₁₆H₁₆ClN₃O₂
• 分子量: 317.775
• InChiKey: KJSQQRAYGDVNNP-UHFFFAOYSA-N

物化性质

• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  48.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-chloro-3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine 在 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 44.0h， 生成 2-((3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-yl)amino)ethyl acetate hydrochloride
  参考文献：
  名称：

  Highly Selective Phosphatidylinositol 4-Kinase IIIβ Inhibitors and Structural Insight into Their Mode of Action

  摘要：

  Phosphatidylinositol 4-kinase III beta is a cellular lipid kinase pivotal to pathogenesis of various RNA viruses. These viruses hijack the enzyme in order to modify the structure of intracellular membranes and use them for the construction of functional replication machinery. Selective inhibitors of this enzyme are potential broad-spectrum antiviral agents, as inhibition of this enzyme results in the arrest of replication of PI4K III beta-dependent viruses. Herein, we report a detailed study of novel selective inhibitors of PI4K III beta, which exert antiviral activity against a panel of single-stranded positive-sense RNA viruses. Our crystallographic data show that the inhibitors occupy the binding site for the adenine ring of the ATP molecule and therefore prevent the phosphorylation reaction.

  DOI：

  10.1021/acs.jmedchem.5b00499
• 作为产物：
  描述：

  3,4-二甲氧基苯乙腈 在 sodium hydride 、 溶剂黄146 、 肼 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 、 乙腈 、 mineral oil 为溶剂， 反应 24.0h， 生成 7-chloro-3-(3,4-dimethoxyphenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  从3-溴-7-苯氧基吡唑并[1,5 - a ]嘧啶中间体轻松制备7-氨基-3-芳基吡唑并[1,5- a ]嘧啶的酚盐离去基团S N Ar策略

  摘要：

  我们已经发现了3-溴-7-苯氧基吡唑并[1,5-a]嘧啶中间体，该中间体允许吡唑并[1,5-a]嘧啶支架的3位和7位直接顺序功能化。本文所述的中间方法和一般方法提供了对现有方法的改进，特别是在多个独特的3-芳基取代基与多个独特的7-氨基取代基结合引入的情况下。

  DOI：

  10.1016/j.tetlet.2015.09.068

文献信息

• PYRAZOLO[1,5-A]PYRIMIDINES AS ANTIVIRAL COMPOUNDS
  申请人：APODEMUS AB

  公开号：US20160318937A1

  公开（公告）日：2016-11-03

  A compound of formula (I) or a pharmaceutically acceptable salt thereof, useful in therapy, in particular in the treatment of a viral infection.

  式（I）的化合物或其在治疗中有用的药用盐，特别是用于治疗病毒感染。
• A novel and potent brain penetrant inhibitor of extracellular vesicle release
  作者：Camilo Rojas、Michal Sala、Ajit G. Thomas、Amrita Datta Chaudhuri、Seung‐Wan Yoo、Zhigang Li、Ranjeet P. Dash、Rana Rais、Norman J. Haughey、Radim Nencka、Barbara Slusher

  DOI：10.1111/bph.14789

  日期：2019.10

  Unfortunately, known inhibitors exhibit μM potency, poor physicochemical properties, and/or limited brain penetration. Here, we sought to identify a drug-like inhibitor of nSMase2. EXPERIMENTAL APPROACH We conducted a human nSMase2 high throughput screen (>365,000 compounds). Selected hits were optimized focusing on potency, selectivity, metabolic stability, pharmacokinetics, and ability to inhibit EV release

  背景和目的 细胞外囊泡 (EVs) 组成性地从细胞中脱落并通过各种刺激释放。它们的蛋白质和 RNA 货物被刺激修饰，并且在疾病条件下可以携带与疾病进展有关的病理货物。中性鞘磷脂酶 2 (nSMase2) 是 EV 生物发生的几种独立途径中至少一种的主要调节剂，其抑制是一种有前途的神经系统疾病的新治疗方法。不幸的是，已知的抑制剂表现出 μM 效力、较差的物理化学性质和/或有限的脑渗透。在这里，我们试图确定一种 nSMase2 的药物样抑制剂。实验方法 我们进行了人类 nSMase2 高通量筛选（>365,000 种化合物）。对选定的命中进行了优化，重点关注效力、选择性、代谢稳定性、药代动力学、以及在体外和体内抑制 EV 释放的能力。关键结果 我们鉴定了苯基(R)-(1-(3-(3,4-二甲氧基苯基)-2,6-二甲基咪唑并[1,2-b]哒嗪-8-基)吡咯烷-3-基)-氨基甲酸酯( PDDC)，一种有效的
• Optimization of 3-phenylpyrazolo[1,5- a ]pyrimidines as potent corticotropin-releasing factor-1 antagonists with adequate lipophilicity and water solubility
  作者：Chen Chen、Keith M Wilcoxen、Charles Q Huang、James R McCarthy、Takung Chen、Dimitri E Grigoriadis

  DOI：10.1016/j.bmcl.2004.05.019

  日期：2004.7

  In our efforts to identify potent CRF1 antagonists with proper physicochemical properties, a series of 3-phenylpyrazolo[1,5-a]pyrimidines bearing polar groups, such as amino, hydroxyl, methoxy, sulfoxide, were designed and synthesized. Several positions of the core structure were identified, where a polar group was tolerated with slight reduction in receptor binding. NBI 30545 (18n) was found to have good binding affinity and potent antagonistic activity at the human CRF1 receptor. Moreover, this compound had proper lipophilicity (log D = 2.78) and good solubility in water (>10 mg/mL), and exhibited good plasma and brain exposure when given orally. (C) 2004 Elsevier Ltd. All rights reserved.
• US9963455B2
  申请人：——

  公开号：US9963455B2

  公开（公告）日：2018-05-08
• [EN] PYRAZOLO[1,5-A]PYRIMIDIN-7-AMINE DERIVATIVES USEFUL IN THERAPY<br/>[FR] DÉRIVÉS DE PYRAZOLO[1,5-A]PYRIMIDINE -7-AMINE UTILES EN THÉRAPIE
  申请人：APODEMUS AB

  公开号：WO2015110491A2

  公开（公告）日：2015-07-30

  A compound of formula (I) or a pharmaceutically acceptable salt thereof, useful in therapy, in particular in the treatment of a viral infection.