(5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonyl)methane | 286009-37-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: (5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonyl)methane
• 英文别名: 2-methanesulfonyl-5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine；2-methanesulfonyl-5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine；5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-methylsulfone；2-(Methanesulfonyl)-5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine；5,7-dimethyl-2-methylsulfonyl-[1,2,4]triazolo[1,5-a]pyrimidine
• CAS: 286009-37-8
• 化学式: C₈H₁₀N₄O₂S
• 分子量: 226.259
• InChiKey: KQMPPUWJGXCQMN-UHFFFAOYSA-N

物化性质

• 熔点：
  187-188 °C
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  85.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonyl)methane 在 硫酸 、 水 、 sodium hydride 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 1.0h， 生成 3-((5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)oxy)-5-methyl-4′-nitro-[1,1′-biphenyl]-2-carboxylic acid
  参考文献：
  名称：

  Triazolopyrimidines as a New Herbicidal Lead for Combating Weed Resistance Associated with Acetohydroxyacid Synthase Mutation

  摘要：

  Acetohydroxyacid synthase (AHAS; also known as acetolactate synthase; EC 2.2.1.6, formerly EC 4.1.3.18) is the first common enzyme in the biosynthetic pathway leading to the branched-chain amino acids in plants and a wide range of microorganisms. Weed resistance to AHAS-inhibiting herbicides, increasing at an exponential rate, is becoming a global problem and leading to an urgent demand of developing novel compounds against both resistant and wild AHAS. In the present work, a series of novel 2-aroxyl-1,2,4-triazolopyrimidine derivatives (a total of 55) were designed and synthesized with the aim to discover an antiresistant lead compound. Fortunately, the screening results indicated that many of the newly synthesized compounds showed a better, even excellent, inhibition effect against both the wild-type Arabidopsis thaliana AHAS and P197L mutants. Among them, compounds 5-3 to 5-17, compounds 5-19 to 5-26, compounds 5-28 to 5-45, and compound 5-48 have the lower values of resistance factor (RF) and display a potential power to overcome resistance associated with the P197L mutation in the enzyme levels. Further greenhouse in vivo assay showed that compounds 5-15 and 5-20 displayed "moderate" to "good" herbicidal activity against both the wild type-and the resistant (P197L mutation) Descurainia sophia, even at a rate as low as 0.9375 (g of ai/ha). The above results indicated that these two compounds could be used as new leads for the future development of antiresistance herbicides.

  DOI：

  10.1021/acs.jafc.6b00720
• 作为产物：
  描述：

  5,7-二甲基-2-(甲基硫烷基)-[1,2,4]三唑并[1,5-a]嘧啶 在 sodium tungstate (VI) dihydrate 、 双氧水 作用下， 以 水 、 溶剂黄146 为溶剂， 以67%的产率得到(5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonyl)methane
  参考文献：
  名称：

  Discovery and Characterization of Nonpeptidyl Agonists of the Tissue-Protective Erythropoietin Receptor

  摘要：

  红细胞生成素（EPO）及其受体在多种组织中表达，包括中枢神经系统。在受伤或压力情况下，EPO及其受体的局部表达上调，在组织稳态和细胞保护中发挥作用。高剂量全身给药或局部注射重组人EPO在多个组织保护和器官损伤模型中显示出令人鼓舞的结果，但该蛋白在组织中的可用性差限制了其疗效。在此，我们描述了一种非肽类化合物STS-E412（2-[2-(4-氯苯氧基)乙氧基]-5,7-二甲基-[1,2,4]三唑[1,5-a] 嘧啶）的发现及特征，该化合物选择性地激活组织保护性EPO受体，包含EPO受体亚单位（EPOR）和共同β链（CD131）。STS-E412在人体神经细胞中诱导EPO受体磷酸化。STS-E412还增加了在表达EPOR和CD131的HEK293转染细胞中EPOR、CD131以及与EPO相关的信号分子JAK2和AKT的磷酸化。在低纳摩尔浓度下，STS-E412在初级神经元细胞和肾小管上皮细胞中提供了类似EPO的细胞保护效应。STS-E412的受体选择性通过以下方式得到验证：EPOR/EPOR同二聚体的磷酸化缺失、在非靶标选择性筛选中的活性缺失，以及在红细胞白血病细胞系TF-1和CD34+前体细胞中的功能效应缺失。通过人工膜和Caco-2细胞单层的渗透性，及其在体内穿越血脑屏障的能力，提示该化合物在中枢神经系统中的可用性潜力。据我们所知，STS-E412是首个非肽类的组织保护性EPOR/CD131受体选择性激活剂。进一步评估STS-E412在中枢神经系统疾病和器官保护中的潜力是必要的。

  DOI：

  10.1124/mol.115.098400

文献信息

• SUBSTITUTED TRIAZOLO-PYRIMIDINE COMPOUNDS FOR MODULATING CELL PROLIFERATION, DIFFERENTIATION AND SURVIVAL
  申请人：STATegics, Inc.

  公开号：US20140142122A1

  公开（公告）日：2014-05-22

  Disclosed herein are erythropoietin-mimetic compounds of Formula I, which modulate the survival, function, or differentiation of, for example, kidney cells, neurons, erythroid cells, or other erythropoietin-responsive cells. The present invention also relates to compounds and methods that preferentially modulate cells expressing the tissue-protective erythropoietin receptor. The compounds of the invention are useful in preventing and treating diseases, such as anemia, organ injury, and diseases of the central nervous system, and as an adjunct to cellular treatments, such as stem cell therapies.

  本公开涉及的是式I的类似促红细胞生成素化合物，其调节肾脏细胞、神经元、红细胞或其他促红细胞生成素反应细胞的存活、功能或分化。本发明还涉及优先调节表达组织保护性促红细胞生成素受体的细胞的化合物和方法。本发明的化合物在预防和治疗贫血、器官损伤、中枢神经系统疾病等疾病方面有用，并可作为干细胞治疗等细胞治疗的辅助手段。
• Discovery and Characterization of Nonpeptidyl Agonists of the Tissue-Protective Erythropoietin Receptor
  作者：James L. Miller、Timothy J. Church、Dmitri Leonoudakis、Karen Lariosa-Willingham、Normand L. Frigon、Connie S. Tettenborn、Jeffrey R. Spencer、Juha Punnonen

  DOI：10.1124/mol.115.098400

  日期：2015.8

  Erythropoietin (EPO) and its receptor are expressed in a wide variety of tissues, including the central nervous system. Local expression of both EPO and its receptor is upregulated upon injury or stress and plays a role in tissue homeostasis and cytoprotection. High-dose systemic administration or local injection of recombinant human EPO has demonstrated encouraging results in several models of tissue protection and organ injury, while poor tissue availability of the protein limits its efficacy. Here, we describe the discovery and characterization of the nonpeptidyl compound STS-E412 (2-[2-(4-chlorophenoxy)ethoxy]-5,7-dimethyl-[1,2,4]triazolo[1,5- a ]pyrimidine), which selectively activates the tissue-protective EPO receptor, comprising an EPO receptor subunit (EPOR) and the common β -chain (CD131). STS-E412 triggered EPO receptor phosphorylation in human neuronal cells. STS-E412 also increased phosphorylation of EPOR, CD131, and the EPO-associated signaling molecules JAK2 and AKT in HEK293 transfectants expressing EPOR and CD131. At low nanomolar concentrations, STS-E412 provided EPO-like cytoprotective effects in primary neuronal cells and renal proximal tubular epithelial cells. The receptor selectivity of STS-E412 was confirmed by a lack of phosphorylation of the EPOR/EPOR homodimer, lack of activity in off-target selectivity screening, and lack of functional effects in erythroleukemia cell line TF-1 and CD34+ progenitor cells. Permeability through artificial membranes and Caco-2 cell monolayers in vitro and penetrance across the blood-brain barrier in vivo suggest potential for central nervous system availability of the compound. To our knowledge, STS-E412 is the first nonpeptidyl, selective activator of the tissue-protective EPOR/CD131 receptor. Further evaluation of the potential of STS-E412 in central nervous system diseases and organ protection is warranted.

  红细胞生成素（EPO）及其受体在多种组织中表达，包括中枢神经系统。在受伤或压力情况下，EPO及其受体的局部表达上调，在组织稳态和细胞保护中发挥作用。高剂量全身给药或局部注射重组人EPO在多个组织保护和器官损伤模型中显示出令人鼓舞的结果，但该蛋白在组织中的可用性差限制了其疗效。在此，我们描述了一种非肽类化合物STS-E412（2-[2-(4-氯苯氧基)乙氧基]-5,7-二甲基-[1,2,4]三唑[1,5-a] 嘧啶）的发现及特征，该化合物选择性地激活组织保护性EPO受体，包含EPO受体亚单位（EPOR）和共同β链（CD131）。STS-E412在人体神经细胞中诱导EPO受体磷酸化。STS-E412还增加了在表达EPOR和CD131的HEK293转染细胞中EPOR、CD131以及与EPO相关的信号分子JAK2和AKT的磷酸化。在低纳摩尔浓度下，STS-E412在初级神经元细胞和肾小管上皮细胞中提供了类似EPO的细胞保护效应。STS-E412的受体选择性通过以下方式得到验证：EPOR/EPOR同二聚体的磷酸化缺失、在非靶标选择性筛选中的活性缺失，以及在红细胞白血病细胞系TF-1和CD34+前体细胞中的功能效应缺失。通过人工膜和Caco-2细胞单层的渗透性，及其在体内穿越血脑屏障的能力，提示该化合物在中枢神经系统中的可用性潜力。据我们所知，STS-E412是首个非肽类的组织保护性EPOR/CD131受体选择性激活剂。进一步评估STS-E412在中枢神经系统疾病和器官保护中的潜力是必要的。
• Synthesis and herbicidal activity of<i>O,O</i>-dialkyl<i>N</i>-[2-(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yloxy)benzoxyl]-1-amino-1-substitutedbenzyl phosphonates
  作者：Wu Tang、De-Qing Shi

  DOI：10.1002/jhet.292

  日期：——

  of novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives containing an α-amino phosphonate moiety were designed and synthesized by the multi-step reactions. Their structures were clearly confirmed by spectroscopic data (IR, 1H NMR, 31P NMR, MS) and elemental analysis, compound was further determined by X-ray diffraction crystallography. The results of preliminary bioassay indicated that some of the title

  一系列含有α-氨基膦酸酯部分的新型1,2,4-三唑并[1,5-a]嘧啶衍生物 通过多步反应设计和合成。通过光谱数据（IR，1 H NMR，31 P NMR，MS）和元素分析清楚地确认了它们的结构，通过X射线衍射晶体学进一步确定。初步生物测定的结果表明，一些标题化合物在100 mg / L的浓度下对双子叶植物（甘蓝型油菜）具有中等的除草活性。例如，化合物对野菜双歧杆菌（B. campestris L）具有92.0％的抑制活性，并且比商品化的除草剂双嘧贝酸钠具有更好的活性。但是，化合物 在10 mg / LJ Heterocyclic Chem。，（2010）的浓度下显示弱的除草活性。
• Substituted triazolo-pyrimidine compounds for modulating cell proliferation differentiation and survival
  申请人：STATegics, Inc.

  公开号：US09163027B2

  公开（公告）日：2015-10-20

  Disclosed herein are erythropoietin-mimetic compounds of Formula I, which modulate the survival, function, or differentiation of, for example, kidney cells, neurons, erythroid cells, or other erythropoietin-responsive cells. The present invention also relates to compounds and methods that preferentially modulate cells expressing the tissue-protective erythropoietin receptor. The compounds of the invention are useful in preventing and treating diseases, such as anemia, organ injury, and diseases of the central nervous system, and as an adjunct to cellular treatments, such as stem cell therapies.

  本文披露了公式I的类似促红细胞生成素化合物，它们可以调节肾细胞、神经元、红细胞或其他对促红细胞生成素敏感的细胞的生存、功能或分化。本发明还涉及优先调节表达组织保护性促红细胞生成素受体的细胞的化合物和方法。本发明的化合物可用于预防和治疗贫血、器官损伤和中枢神经系统疾病，并作为细胞治疗（如干细胞治疗）的辅助治疗。
• A convenient route to synthesize 1,2,4-triazolo[1,5-<i>a</i>]pyrimidine derivatives and their one and two-photon absorption spectral properties
  作者：Hongli Wang、Wenyuan Xu、Yi Dai、Bin Zhang、Qiongyou Wu、Mingzhi Zhang、Min Tian、Hong Wu、Dingli Wang

  DOI：10.1002/jhet.5570440502

  日期：2007.9

  A convenient method for synthesizing α-(1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonyl)methane derivatives, 3 and 4, by the well known Knoevenagel reaction, in one step, is described. The two chromophores are stilbene-type chromophores containing the same D-π-A structures and end-capped with aromatic group as their donors. Measured with femtosecond multipass Ti:sapphire amplifier as irradiation source

  描述了一种通过众所周知的Knoevenagel反应一步合成α-（1,2,4-三唑并[1,5- a ]嘧啶-2-磺酰基）甲烷衍生物3和4的简便方法。这两个生色团是二苯乙烯型生色团，其具有相同的D-π-A结构，并以其供体端基被芳族基团封端。用飞秒多通Ti：蓝宝石放大器作为辐照源（由800 nm的激光泵浦）测量，两个生色团显示出有效的双光子诱导的橙红色荧光发射。实验结果表明，两个生色团的分支数目影响其单光子性质和两光子上转换发射行为，并且随着分支数目的增加，它们的波长为λabs max，λspf max和λtpf max表现出红移。