1-甲基-1H-1,2,4-噻唑-5-甲胺 | 244639-03-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 1-甲基-1H-1,2,4-噻唑-5-甲胺
• 中文别名: 1-甲基-1H-1,2,4-三唑-5-甲胺
• 英文名称: (1-methyl-1H-1,2,4-triazol-5-yl)-methanamin
• 英文别名: 1-Methyl-1H-1,2,4-triazole-5-methanamine；(2-methyl-1,2,4-triazol-3-yl)methanamine
• CAS: 244639-03-0
• 化学式: C₄H₈N₄
• mdl: MFCD06410879
• 分子量: 112.134
• InChiKey: UYDIYTPFKQIUCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  56.7
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  1-甲基-1H-1,2,4-噻唑-5-甲胺 、 7-chloro-2,5-dimethyl-3-phenylpyrazolo[1,5-a]pyrimidine 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 反应 16.0h， 以89%的产率得到2,5-dimethyl-N-((1-methyl-1H-1,2,4-triazol-5-yl)methyl)-3-phenylpyrazolo [1,5-a]pyrimidin-7-amine
  参考文献：
  名称：

  Aminopyrazolo[1,5-a]pyrimidines as potential inhibitors of Mycobacterium tuberculosis: Structure activity relationships and ADME characterization

  摘要：

  Whole-cell high-throughput screening of a diverse SoftFocus library against Mycobacterium tuberculosis (Mtb) generated a novel aminopyrazolo[1,5-a]pyrimidine hit series. The synthesis and structure activity relationship studies identified compounds with potent antimycobacterial activity. The SAR of over 140 compounds shows that the 2-pyridylmethylamine moiety at the C-7 position of the pyrazolopyrimidine scaffold was important for Mtb activity, whereas the C-3 position offered a higher degree of flexibility. The series was also profiled for in vitro cytotoxicity and microsomal metabolic stability as well as physicochemical properties. Consequently liabilities to be addressed in a future lead optimization campaign have been identified. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.10.021

文献信息

• 10.1021/acs.jmedchem.4c00215
  作者：Carlino, Luca、Astles, Peter C.、Ackroyd, Bryony、Ahmed, Afshan、Chan, Christina、Collie, Gavin W.、Dale, Ian L.、O’Donovan, Daniel H.、Fawcett, Caroline、di Fruscia, Paolo、Gohlke, Andrea、Guo, Xiaoxiao、Hao-Ru Hsu, Jessie、Kaplan, Bethany、Milbradt, Alexander G.、Northall, Sarah、Petrović, Dušan、Rivers, Emma L.、Underwood, Elizabeth、Webb, Alice

  DOI：10.1021/acs.jmedchem.4c00215

  日期：——

  multidomain protein that carries histone writing and histone reading functions. To date, identifying inhibitors of the enzymatic activity of NSD2 has proven challenging in terms of potency and SET domain selectivity. Inhibition of the NSD2-PWWP1 domain using small molecules has been considered as an alternative approach to reduce NSD2-unregulated activity. In this article, we present novel computational chemistry

  组蛋白甲基转移酶核受体结合 SET 结构域 2 (NSD2) 的失调与多种血液和实体恶性肿瘤有关。 NSD2 是一种大型多结构域蛋白，具有组蛋白写入和组蛋白读取功能。迄今为止，鉴定 NSD2 酶活性抑制剂在效力和 SET 结构域选择性方面具有挑战性。使用小分子抑制 NSD2-PWWP1 结构域被认为是减少 NSD2 不受调控的活性的替代方法。在本文中，我们提出了新颖的计算化学方法，包括与机器学习 (FEP/ML) 模型耦合的自由能扰动以及虚拟筛选 (VS) 活动，以识别高亲和力 NSD2 PWWP1 结合物。通过这些活动，我们确定了迄今为止文献中报道的最有效的 NSD2-PWWP1 结合剂：化合物34 (pIC 50 = 8.2)。本文鉴定的化合物代表了研究 PWWP1 结构域抑制人 NSD2 的作用的有用工具。
• [EN] INDUCERS OF KLF2 AND METHODS OF USE THEREOF<br/>[FR] INDUCTEURS DE KLF2 ET LEURS PROCÉDÉS D'UTILISATION
  申请人：[en]RIPARIAN PHARMACEUTICALS, INC.

  公开号：WO2023150374A1

  公开（公告）日：2023-08-10

  The present disclosure provides compounds that are inducers of KLF2 and pharmaceutical compositions comprising the same. The present disclosure further provides method of treating an inflammatory disease or endothelial dysfunction comprising administering a therapeutically effective amount of the compounds disclosed herein.
• Aminopyrazolo[1,5-a]pyrimidines as potential inhibitors of Mycobacterium tuberculosis: Structure activity relationships and ADME characterization
  作者：Candice Soares de Melo、Tzu-Shean Feng、Renier van der Westhuyzen、Richard K. Gessner、Leslie J. Street、Garreth L. Morgans、Digby F. Warner、Atica Moosa、Krupa Naran、Nina Lawrence、Helena I.M. Boshoff、Clifton E. Barry、C. John Harris、Richard Gordon、Kelly Chibale

  DOI：10.1016/j.bmc.2015.10.021

  日期：2015.11

  Whole-cell high-throughput screening of a diverse SoftFocus library against Mycobacterium tuberculosis (Mtb) generated a novel aminopyrazolo[1,5-a]pyrimidine hit series. The synthesis and structure activity relationship studies identified compounds with potent antimycobacterial activity. The SAR of over 140 compounds shows that the 2-pyridylmethylamine moiety at the C-7 position of the pyrazolopyrimidine scaffold was important for Mtb activity, whereas the C-3 position offered a higher degree of flexibility. The series was also profiled for in vitro cytotoxicity and microsomal metabolic stability as well as physicochemical properties. Consequently liabilities to be addressed in a future lead optimization campaign have been identified. (C) 2015 Elsevier Ltd. All rights reserved.