5-(2-methoxyphenyl)-4-methyl-4H-1,2,4-triazole-3-thiol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(2-methoxyphenyl)-4-methyl-4H-1,2,4-triazole-3-thiol
• 英文别名: 3-(2-methoxyphenyl)-4-methyl-1H-1,2,4-triazole-5-thione
• 化学式: C₁₀H₁₁N₃OS
• mdl: MFCD02091580
• 分子量: 221.283
• InChiKey: QTQYEVBKWNUVNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  69
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(3-Chloropropyl)-7-(5-methyl-isoxazol-3-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine 、 5-(2-methoxyphenyl)-4-methyl-4H-1,2,4-triazole-3-thiol 在 sodium iodide potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 3-[3-[3-[[5-(2-Methoxyphenyl)-4-methyl-1,2,4-triazol-3-yl]sulfanyl]propyl]-1,2,4,5-tetrahydro-3-benzazepin-7-yl]-5-methyl-1,2-oxazole
  参考文献：
  名称：

  1,2,4-Triazol-3-yl-thiopropyl-tetrahydrobenzazepines:  A Series of Potent and Selective Dopamine D₃ Receptor Antagonists

  摘要：

  The discovery of new highly potent and selective dopamine D-3 receptor antagonists has recently permitted characterization of the role of the dopamine D-3 receptor in a wide range, of preclinical animal models. A novel series of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines demonstrating a high level of D3 affinity and selectivity with an excellent pharmacokinetic profile is reported here. In particular, the pyrazolyl derivative 35 showed good oral bioavailability and brain penetration associated with high potency and selectivity in vitro. In vivo characterization of 35 confirmed that this compound blocks the expression of nicotine- and cocaine-conditioned place preference in the rat, prevents nicotine-triggered reinstatement of nicotine- seeking behavior in the rat, reduces oral operant alcohol self- administration in the mouse, increases extracellular levels of acetylcholine in the rat medial prefrontal cortex, and potentiates the amplitude of the relative cerebral blood volume response to d-amphetamine in a regionally specific manner in the rat brain.

  DOI：

  10.1021/jm0705612
• 作为产物：
  描述：

  2-甲氧基亚苯基肼 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 12.17h， 生成 5-(2-methoxyphenyl)-4-methyl-4H-1,2,4-triazole-3-thiol
  参考文献：
  名称：

  1-[（1R，2S）-2-氟丙基]环丙沙星-（4-甲基-3-芳基）-1,2,4-三唑-5（4H）-亚硫杂基的设计，合成和抗菌评估

  摘要：

  设计，合成了十四种新型的1-[（（1R，2S）-2-氟环丙基]环丙沙星-（4-甲基-3-芳基）-1,2,4-三唑-5（4H）-硫酮杂化物6a-n。并评估了它们对代表性革兰氏阳性和革兰氏阴性细菌的体外抗菌活性。所有杂种6a-n都显示出有希望的抗菌活性，尤其是对革兰氏阴性病原体的抗菌活性，有待进一步研究。

  DOI：

  10.33224/rrch.2019.64.1.10

文献信息

• Synthesis, Antifungal Activity, 3D-QSAR, and Molecular Docking Study of Novel Menthol-Derived 1,2,4-Triazole-thioether Compounds
  作者：Mei Huang、Wen-Gui Duan、Gui-Shan Lin、Bao-Yu Li

  DOI：10.3390/molecules26226948

  日期：——

  displayed antifungal activity of 90.5% and 83.8%, respectively, against Colleterichum orbicalare and Fusarium oxysporum f. sp. cucumerinum. Compounds 5m (R = o-I Ph) had inhibition rates of 88.6%, 80.0%, and 88.0%, respectively, against F.oxysporum f. sp. cucumerinu, Bipolaris maydis and C. orbiculare. Furthermore, compound 5b (R = o-CH3 Ph) showed the best and broad-spectrum antifungal activity against

  设计、合成了一系列含有1,2,4-三唑-硫醚部分的新型薄荷醇衍生物，对其进行结构表征并进行生物学评估，以探索更有效的基于天然产物的抗真菌剂。生物测定结果表明，部分目标化合物在50 μg/mL浓度下对受试真菌，特别是对梨轮纹孢菌表现出良好的抑制活性。化合物5b (R= o -CH 3 Ph)、5i (R= o -Cl Ph)、5v (R= m,p -OCH 3 Ph)和5x (R= α-呋喃基)的抑制率为93.3％，对P. piricola 的抑制效果分别为 79.4% 和 79.4% ，远优于阳性对照百菌清。化合物5v（R= m，p -OCH 3 Ph）和5g（R= o -Cl Ph）对花生尾孢和玉米赤霉的抑制率分别为82.4%和86.5% ，远优于市售杀菌剂百菌清。 。化合物5b (R = o -CH 3 Ph)对Colleterichum orbicalare和Fusarium oxysporum
• Certain triazole-based compounds, compositions, and uses thereof
  申请人：Hodge Nicholas Carl

  公开号：US20050288347A1

  公开（公告）日：2005-12-29

  Thiotriazole-based chemical entities exhibiting ATP-utilizing enzyme inhibitory activity, methods of using such chemical entities, and compositions comprising such chemical entities, are described.

  描述了具有 ATP 利用酶抑制活性的硫代三唑类化学实体、使用此类化学实体的方法以及包含此类化学实体的组合物。
• Leveraging a Low-Affinity Diazaspiro Orthosteric Fragment to Reduce Dopamine D₃ Receptor (D₃R) Ligand Promiscuity across Highly Conserved Aminergic G-Protein-Coupled Receptors (GPCRs)
  作者：Sean W. Reilly、Aladdin A. Riad、Chia-Ju Hsieh、Kristoffer Sahlholm、Daniel A. Jacome、Suzy Griffin、Michelle Taylor、Chi-Chang Weng、Kuiying Xu、Nathan Kirschner、Robert R. Luedtke、Christopher Parry、Shipra Malhotra、John Karanicolas、Robert H. Mach

  DOI：10.1021/acs.jmedchem.9b00412

  日期：2019.5.23

  Previously, we reported a 3-(2-methoxyphenyl)-9-(3-((4-methyl-5-phenyl-4H-1,2,4-triazol-3-yl)thio)-propyl)-3,9-diazaspiro[5.5]undecane (1) compound with excellent dopamine D-3 receptor (D3R) affinity (D3R K-i = 12.0 nM) and selectivity (D2R/D3R ratio = 905). Herein, we present derivatives of 1 with comparable D3R affinity (32, D3R K-i = 3.2 nM, D2R/D3R ratio = 60) and selectivity (30, D3R K-i = 21.0 nM, D2R/D3R ratio = 934). Fragmentation of 1 revealed orthosteric fragment 5a to express an unusually low D3R affinity (K-i = 2.7 mu M). Compared to piperazine congener 31, which retains a high-affinity orthosteric fragment (5d, D3R K-i = 23.9 nM), 1 was found to be more selective for the D3R among D-1- and D-2-like receptors and exhibited negligible off-target interactions at serotoninergic and adrenergic G-protein-coupled receptors (GPCRs), common off-target sites for piperazine-containing D3R scaffolds. This study provides a unique rationale for implementing weakly potent orthosteric fragments into D3R ligand systems to minimize drug promiscuity at other aminergic GPCR sites.
• 1,2,4-Triazol-3-yl-thiopropyl-tetrahydrobenzazepines:  A Series of Potent and Selective Dopamine D₃ Receptor Antagonists
  作者：Fabrizio Micheli、Giorgio Bonanomi、Frank E. Blaney、Simone Braggio、Anna Maria Capelli、Anna Checchia、Ornella Curcuruto、Federica Damiani、Romano Di Fabio、Daniele Donati、Gabriella Gentile、Andy Gribble、Dieter Hamprecht、Giovanna Tedesco、Silvia Terreni、Luca Tarsi、Andrew Lightfoot、Geoff Stemp、Gregor MacDonald、Alex Smith、Michela Pecoraro、Marcella Petrone、Ornella Perini、Jacqui Piner、Tino Rossi、Angela Worby、Maria Pilla、Enzo Valerio、Cristiana Griffante、Manolo Mugnaini、Martyn Wood、Claire Scott、Michela Andreoli、Laurent Lacroix、Adam Schwarz、Alessandro Gozzi、Angelo Bifone、Charles R. Ashby,、Jim J. Hagan、Christian Heidbreder

  DOI：10.1021/jm0705612

  日期：2007.10.1

  The discovery of new highly potent and selective dopamine D-3 receptor antagonists has recently permitted characterization of the role of the dopamine D-3 receptor in a wide range, of preclinical animal models. A novel series of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines demonstrating a high level of D3 affinity and selectivity with an excellent pharmacokinetic profile is reported here. In particular, the pyrazolyl derivative 35 showed good oral bioavailability and brain penetration associated with high potency and selectivity in vitro. In vivo characterization of 35 confirmed that this compound blocks the expression of nicotine- and cocaine-conditioned place preference in the rat, prevents nicotine-triggered reinstatement of nicotine- seeking behavior in the rat, reduces oral operant alcohol self- administration in the mouse, increases extracellular levels of acetylcholine in the rat medial prefrontal cortex, and potentiates the amplitude of the relative cerebral blood volume response to d-amphetamine in a regionally specific manner in the rat brain.
• DESIGN, SYNTHESIS AND ANTIBACTERIAL EVALUATION OF 1-[(1R,2S)-2-FLUOROCYCLOPROPYL] CIPROFLOXACIN-(4-METHYL-3-ARYL)-1,2,4-TRIAZOLE-5(4H)-THIONE HYBRIDS
  作者：Yun-He GENG、Zeng-Quan WEI、Zhi XU、Lu-Xin NA、Shu ZHANG、Hui-Yuan GUO、Ming-Liang LIU、Lian-Shun FENG、Xue-Fu YOU

  DOI：10.33224/rrch.2019.64.1.10

  日期：——

  Fourteen novel 1-[(1R,2S)-2-Fluorocyclopropyl]ciprofloxac in-(4-methyl-3-aryl)-1,2,4-triazole-5(4H)-thione hybrids 6a-n were designed, synthesized and assessed for their in vitro antibacterial activities against representative Gram-positive and Gram-negative bacteria. All hybrids 6a-n exhibited promising antibacterial activity, especially against Gram-negative pathogens, warrant further investigation

  设计，合成了十四种新型的1-[（（1R，2S）-2-氟环丙基]环丙沙星-（4-甲基-3-芳基）-1,2,4-三唑-5（4H）-硫酮杂化物6a-n。并评估了它们对代表性革兰氏阳性和革兰氏阴性细菌的体外抗菌活性。所有杂种6a-n都显示出有希望的抗菌活性，尤其是对革兰氏阴性病原体的抗菌活性，有待进一步研究。