4-amino-1-tert-butyl-pyrazolo[3,4-d] pyrimidin-3-ol | 1151651-82-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 4-amino-1-tert-butyl-pyrazolo[3,4-d] pyrimidin-3-ol
• 英文别名: 4-amino-1-tert-butyl-1H-pyrazolo[3,4-d]pyrimidin-3-ol；4-amino-1-tert-butyl-2H-pyrazolo[3,4-d]pyrimidin-3-one
• CAS: 1151651-82-9
• 化学式: C₉H₁₃N₅O
• 分子量: 207.235
• InChiKey: KIVGHWGMBFJXTQ-UHFFFAOYSA-N

物化性质

• 密度：
  1.319±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  84.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-amino-1-tert-butyl-pyrazolo[3,4-d] pyrimidin-3-ol 在 硫酸 、 potassium carbonate 、 caesium carbonate 作用下， 以 N,N-二甲基乙酰胺 、 二甲基亚砜 为溶剂， 反应 20.0h， 生成 1-[(trans)-2-benzyloxycyclohexyl]-3-[[4-(trifluoromethyl)-2-pyridyl]oxy]pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  CDPK1 INHIBITORS, COMPOSITIONS, AND METHODS RELATED THERETO

  摘要：

  该发明涉及钙依赖性蛋白激酶1（CDPK1）的抑制剂及其药物制剂。该发明进一步涉及使用该发明的新型抑制剂治疗寄生虫感染的方法，例如弓形虫、疟原虫、人类小肠球虫或小肠球小弓形虫感染。

  公开号：

  US20210347780A1
• 作为产物：
  描述：

  1-(tert-butyl)-3-methoxy-1H-pyrazolo[3,4-d]pyrimidin-4-amine 在 三甲基氯硅烷 、 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 36.0h， 以72%的产率得到4-amino-1-tert-butyl-pyrazolo[3,4-d] pyrimidin-3-ol
  参考文献：
  名称：

  Identification of pyrazolopyrimidine arylsulfonamides as CC-chemokine receptor 4 (CCR4) antagonists

  摘要：

  A novel 4-aminoindazole sulfonamide hit (13) was identified as a human CCR4 antagonists from testing a focussed library of compounds in the primary GTPcS assay. Replacing the indazole core with a pyrazolopyrimidine, and introduction of a methoxy group adjacent to the sulfonamide substituent, resulted in the identification of pyrazolopyrimidine 37a, which exhibited good binding affinity in the GTPcS assay (pIC(50) = 7.2), low lipophilicity (c logP = 2.2, chromlog D-7.4 = 2.4), high LE (0.41), high solubility (CLND solubility >= 581 mu M), and an excellent PK profile in both the rat (F = 62%) and the dog (F = 100%). Further SAR investigation of the pyrazolopyrimidine suggested that substitution at N1 is tolerated, providing a suitable vector to modulate the properties, and increase the potency in a lead optimisation campaign. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.07.052

文献信息

• Cyclopentane-Based Modulators of STING (Stimulator of Interferon Genes)
  申请人：PFIZER INC.

  公开号：US20190284216A1

  公开（公告）日：2019-09-19

  Compounds of the general formula (I): or a pharmaceutically acceptable salt thereof, processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.

  通式（I）的化合物，或其药用盐，这些化合物的制备方法，含有这些化合物的组合物，以及这些化合物的用途。
• MODULATION OF PROTEIN TRAFFICKING
  申请人：Bulawa Christine Ellen

  公开号：US20100331297A1

  公开（公告）日：2010-12-30

  Compounds and compositions are provided for treatment or amelioration of one or more disorders characterized by defects in protein trafficking. A method of treating a disorder characterized by impaired protein trafficking includes administering to a subject or contacting a cell with a compound of Formula I: [formula here] or pharmaceutically acceptable salts or derivatives thereof.

  本发明提供用于治疗或改善由蛋白质运输缺陷所特征的一个或多个疾病的化合物和组合物。一种治疗由蛋白质运输受损所特征的疾病的方法包括向受试者施用或与细胞接触化合物I的药物或其药学上可接受的盐或衍生物。[公式在此]
• Cyclopentane-based modulators of STING (stimulator of interferon genes)
  申请人：PFIZER INC.

  公开号：US10968242B2

  公开（公告）日：2021-04-06

  Compounds of the general formula (I): or a pharmaceutically acceptable salt thereof, processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.

  通式 (I) 的化合物： 或其药学上可接受的盐、制备这些化合物的工艺、含有这些化合物的组合物以及这些化合物的用途。
• [EN] MODULATION OF PROTEIN TRAFFICKING<br/>[FR] RÉGULATION DU TRAFIC DE PROTÉINES
  申请人：FOLDRX PHARMACEUTICALS INC

  公开号：WO2009062118A3

  公开（公告）日：2009-12-30
• Optimizing Pyrazolopyrimidine Inhibitors of Calcium Dependent Protein Kinase 1 for Treatment of Acute and Chronic Toxoplasmosis
  作者：James W. Janetka、Allen T. Hopper、Ziping Yang、Jennifer Barks、Mary Savari Dhason、Qiuling Wang、L. David Sibley

  DOI：10.1021/acs.jmedchem.0c00419

  日期：2020.6.11

  Calcium dependent protein kinase 1 (CDPK1) is an essential Ser/Thr kinase that controls invasion and egress by the protozoan parasite Toxoplasma gondii. The Gly gatekeeper of CDPK1 makes it exquisitely sensitive to inhibition by small molecule 1H-pyrazolo[3,4-d]pyrimidine-4-amine (PP) compounds that are bulky ATP mimetics. Here we rationally designed, synthesized, and tested a series of novel PP analogs that were evaluated for inhibition of CDPK1 enzyme activity in vitro and parasite growth in cell culture. Optimal substitution on the PP scaffold included 2-pyridyl ethers directed into the hydrophobic pocket and small carbocyclic rings accessing the ribose-binding pocket. Further optimization of the series led to identification of the lead compound 3a that displayed excellent potency, selectivity, safety profile, and efficacy in vivo. The results of these studies provide a foundation for further work to optimize CDPK1 inhibitors for the treatment of acute and chronic toxoplasmosis.