1-(tert-butyl)-3-(quinolin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine | 1363386-38-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-(tert-butyl)-3-(quinolin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
• 英文别名: 1-tert-butyl-3-(quinolin-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine；1-Tert-butyl-3-(6-quinolyl)pyrazolo[3,4-d]pyrimidin-4-amine；1-tert-butyl-3-quinolin-6-ylpyrazolo[3,4-d]pyrimidin-4-amine
• CAS: 1363386-38-2
• 化学式: C₁₈H₁₈N₆
• 分子量: 318.381
• InChiKey: HBSLBUQTXFDDFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  82.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(tert-butyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 ammonium hydroxide 、 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 36.75h， 生成 1-(tert-butyl)-3-(quinolin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  发现吡唑并[3,4-d]嘧啶作为新型丝裂原激活蛋白激酶激酶 3 (MKK3) 抑制剂

  摘要：

  双特异性蛋白激酶 MKK3 与肿瘤细胞增殖和存活有关，但其在癌症中的确切作用仍不确定。阐明激酶参与疾病生物学的关键一步是鉴定有效的细胞渗透性激酶抑制剂。目前，MKK3 缺乏用于这些目的的专用工具化合物，以及用于轻松筛选、鉴定和优化抑制剂的有效方法。在这项研究中，我们开发了一种基于 TR-FRET 的酶测定法，用于体外检测 MKK3 活性，并开发了一种基于 BRET 的测定法，用于评估完整人体细胞内配体与该酶的结合。这些测定有助于识别针对 MKK3 的命中化合物，这些化合物共享来自生物活性激酶抑制剂库的共同化学支架。随后通过合成新颖的类似物扩大了最初的成功。使用针对 MKK3 同源模型的分子动力学模拟，对所得构效关系 (SAR) 进行了合理化。我们期望我们的发现能够加速新型、有效、选择性和生物活性抑制剂的开发，从而促进 MKK3 在各种癌症中的作用的研究。

  DOI：

  10.1016/j.bmc.2023.117561

文献信息

• Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases
  申请人：University of Washington through its Center for Commercialization

  公开号：US10544104B2

  公开（公告）日：2020-01-28

  Compositions and methods for the treatment of toxoplasmosis, caused by the infectious eukaryotic parasite Toxoplasma gondii (T. gondii) and for the treatment of cryptosporidiosis, caused by the infectious eukaryotic parasites Cryptosporidium parvum (C. parvum) and Cryptosporidium hominus (C. hominus) are described. In particular, the present disclosure is directed to compositions and methods for inhibiting either T. gondii calcium dependent protein kinases (TgCDPKs) or C. parvum and C. hominus calcium dependent protein kinases (CpCDPKs) using pyrazolopyrimidine and/or imidazo[1,5-a]pyrazine inhibitors, of the formula, wherein the variables X, Y, Z, L, R1, and R3 are defined herein.

  本发明描述了治疗由传染性真核寄生虫弓形虫（T. gondii）引起的弓形虫病和治疗由传染性真核寄生虫副隐孢子虫（C. parvum）和原隐孢子虫（C. hominus）引起的隐孢子虫病的组合物和方法。特别是，本公开涉及使用式中的吡唑嘧啶和/或咪唑并[1,5-a]吡嗪抑制剂抑制刚地隐孢子虫钙依赖性蛋白激酶（TgCDPKs）或副隐孢子虫和人隐孢子虫钙依赖性蛋白激酶（CpCDPKs）的组合物和方法、 其中变量 X、Y、Z、L、R1 和 R3 在本文中定义。
• Development of <i>Toxoplasma gondii</i> Calcium-Dependent Protein Kinase 1 (<i>Tg</i>CDPK1) Inhibitors with Potent Anti-<i>Toxoplasma</i> Activity
  作者：Steven M. Johnson、Ryan C. Murphy、Jennifer A. Geiger、Amy E. DeRocher、Zhongsheng Zhang、Kayode K. Ojo、Eric T. Larson、B. Gayani K. Perera、Edward J. Dale、Panqing He、Molly C. Reid、Anna M. W. Fox、Natascha R. Mueller、Ethan A. Merritt、Erkang Fan、Marilyn Parsons、Wesley C. Van Voorhis、Dustin J. Maly

  DOI：10.1021/jm201713h

  日期：2012.3.8

  Toxoplasmosis is a disease of prominent health concern that is caused by the protozoan parasite Toxoplasma gondii. Proliferation of T. gondii is dependent on its ability to invade host cells, which is mediated in part by calcium-dependent protein kinase 1 (CDPK1). We have developed ATP competitive inhibitors of TgCDPK1 that block invasion of parasites into host cells, preventing their proliferation. The presence of a unique glycine gatekeeper residue in TgCDPK1 permits selective inhibition of the parasite enzyme over human kinases. These potent TgCDPK1 inhibitors do not inhibit the growth of human cell lines and represent promising candidates as toxoplasmosis therapeutics.
• Compositions And Methods For Treating Toxoplasmosis, Cryptosporidiosis, And Other Apicomplexan Protozoan Related Diseases
  申请人：VAN VOORHIS Wesley C.

  公开号：US20130018040A1

  公开（公告）日：2013-01-17

  Compositions and methods for the treatment of toxoplasmosis, caused by the infectious eukaryotic parasite Toxoplasma gondii ( T. gondii ) and for the treatment of cryptosporidiosis, caused by the infectious eukaryotic parasites Cryptosporidium parvum ( C. parvum ) and Cryptosporidium hominus ( C. hominus ) are described. In particular, the present disclosure is directed to compositions and methods for inhibiting either T. gondii calcium dependent protein kinases (TgCDPKs) or C. parvum and C. hominus calcium dependent protein kinases (CpCDPKs) using pyrazolopyrimidine and/or imidazo[1,5-a]pyrazine inhibitors, of the formula, wherein the variables X, Y, Z, L, R 1 , and R 3 are defined herein.
• Compositions and Methods for Treating Toxoplasmosis, Cryptosporidiosis, and Other Apicomplexan Protozoan Related Diseases
  申请人：University of Washington through its Center for Commercialization

  公开号：US20180022709A1

  公开（公告）日：2018-01-25

  Compositions and methods for the treatment of toxoplasmosis, caused by the infectious eukaryotic parasite Toxoplasma gondii ( T. gondii ) and for the treatment of cryptosporidiosis, caused by the infectious eukaryotic parasites Cryptosporidium parvum ( C. parvum ) and Cryptosporidium hominus ( C. hominus ) are described. In particular, the present disclosure is directed to compositions and methods for inhibiting either T. gondii calcium dependent protein kinases (TgCDPKs) or C. parvum and C. hominus calcium dependent protein kinases (CpCDPKs) using pyrazolopyrimidine and/or imidazo[1,5-a]pyrazine inhibitors, of the formula, wherein the variables X, Y, Z, L, R 1 , and R 3 are defined herein.
• US9765037B2
  申请人：——

  公开号：US9765037B2

  公开（公告）日：2017-09-19