1,4,5-trimethyl-2-mercaptoimidazole | 25433-05-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑啉类
• 英文名称: 1,4,5-trimethyl-2-mercaptoimidazole
• 英文别名: 2-Mercapto-1,4,5-trimethylimidazole；1,4,5-trimethylimidazole-2-thiol；1,4,5-trimethyl-2-thioimidazole；2-mercapto-N,4,5-trimethylimidazole；1,4,5-trimethyl-1H-imidazol-2-thiol；3,4,5-trimethyl-1H-imidazole-2-thione
• CAS: 25433-05-0
• 化学式: C₆H₁₀N₂S
• 分子量: 142.225
• InChiKey: PERWAYOEWJEJNO-UHFFFAOYSA-N

物化性质

• 熔点：
  214-217 °C(Solv: ethyl ether (60-29-7); acetone (67-64-1))
• 沸点：
  187.2±23.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47.4
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1,4,5-trimethyl-2-mercaptoimidazole 在 铁粉 、 sodium hydride 、 氯化铵 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-chloro-4-(1,4,5-trimethyl-1H-imidazol-2-ylsulfanyl)-phenylamine
  参考文献：
  名称：

  Synthesis and evaluation of 4-Anilino-6,7-dialkoxy-3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascade

  摘要：

  4-[3-Chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)]anilino-6,7-diethoxy-3- quinolinecarbonitrile (3) was identified as a MEK1 kinase inhibitor with exceptional activity against LoVo cells. The structure-activity relationships of the C-4 aniline substituents were explored, and water-solubilizing groups were added at the C-7 position to improve physical properties. Secondary cellular assays revealed that a compound possessing the appropriate aniline substituents inhibited MEK1 as well as MAPK phosphorylation, thereby acting as a dual inhibitor of the Ras-MAPK signaling cascade. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00640-1
• 作为产物：
  描述：

  1,4,5-trimethyl-1H-imidazole 3-oxide 在 2,2,4,4-tetramethyl-3-thioxocyclobutanone 作用下， 以 氯仿 为溶剂， 反应 1.0h， 以85%的产率得到1,4,5-trimethyl-2-mercaptoimidazole
  参考文献：
  名称：

  First Examples of Reactions of AzoleN-Oxides with Thioketones: A Novel Type of Sulfur-Transfer Reaction

  摘要：

  The reactions of 1,4,5-trisubstituted imidazole 3-oxides 1a-k with cyclobutanethiones 5a,b in CHCl3 at room temperature give imidazole-2(3H)-thiones 9a-k in high yield. The second product formed in this reaction is 2,2,4,4-tetramethylcyclobutane-1,3-dione (6a; Scheme 2). Similar reactions occur with 1 and adamantanethione (5c) as thiocarbonyl compound, as well as with 1,2,4-triazole-4-oxide derivative 10 and 5a (Scheme 3). A reaction mechanism by a two-step formation of the formal cycloadduct of type 7 via zwitterion 16 is proposed in Scheme 5. Spontaneous decomposition of 7 yields the products of this novel sulfur-transfer reaction. The starting imidazole 3-oxides are conveniently prepared by heating a mixture of 1,3,5-trisubstituted hexahydro-1,3,5-triazines 3 and alpha-(hydroxyimino) ketones 2 in EtOH (cf: Scheme 1). As demonstrated in the case of 9d, a 'one-pot' procedure allows the preparation of 9 without isolation of the imidazole 3-oxides 1. The reaction of Ic with thioketene 12 leads to a mixture of four products (Scheme 4). The minor products, 9c and the ketene 15, result from an analogous sulfur-transfer reaction (Path a in Scheme 5), whereas the parent imidazole 14 and thiiranone 13 are the products of an oxygen-transfer reaction (Path b in Scheme 5).

  DOI：

  10.1002/(sici)1522-2675(19980909)81:9<1585::aid-hlca1585>3.0.co;2-n

文献信息

• 1,4,5-Trialkyl Imidazole System Anti-inflammatory Properties of New Substituted Derivatives.
  作者：Jamal FATIMI、Jean-Francois LAGORCE、Jean-Luc DUROUX、Marie-Laure CHABERNAUD、Jacques BUXERAUD、Claude RABY

  DOI：10.1248/cpb.42.698

  日期：——

  In an investigation of the anti-inflammatory properties of five-membered ring nitrogen-containing heterocyclic compounds, two series of derivatives of imidazole were prepared by altering the sites of substitution and by joining aliphatic chains to the nitrogen atom in the 1 position of the imidazole ring. Some of them were more potent inhibitors of carrageenan-induced edema than indomethacin. An electron

  在研究五元环含氮杂环化合物的抗炎特性时，通过改变取代位置并将脂肪链连接到咪唑的1位氮原子上，制备了咪唑的两个系列衍生物环。与消炎痛相比，它们中的一些是角叉菜胶诱发的水肿的更有效抑制剂。电子自旋共振研究表明这些化合物具有抗自由基活性。
• New Selenosemicarbazides Derived from Imidazole-Based Carbohydrazides
  作者：Adam M. Pieczonka、Krzysztof Ciepielowski、Zofia Cebulska、Grzegorz Mlostoń、Anthony Linden、Heinz Heimgartner

  DOI：10.1002/hlca.201200620

  日期：2013.3

  Imidazole‐based carbohydrazides, i.e., 3‐oxidoimidazole‐4‐carbohydrazides 1 and 2‐[(imidazol‐2‐yl)sulfanyl]acetohydrazides 6, react with aryl isoselenocyanates 4 in MeOH at room temperature to give the corresponding selenosemicarbazides 5 and 7, respectively, in good yields. On heating 7b in DMF in the presence of air to 100°, 1,3,4‐oxadiazole 8a was formed via cyclization and formal elimination of

  咪唑基碳酰肼，即3-氧代咪唑-4-碳酰肼1和2-[（（咪唑-2-基）硫烷基]乙酰]乙酰肼6，在室温下与MeOH中的芳基异亚硒酸酯4反应，得到相应的硒代氨基碳酰肼5和7，分别以高收成。在空气中将7b在DMF中加热到100°，通过环化和正式消除H 2 Se形成1,3,4-恶二唑8a。加热4a和6b的混合物后，也获得了产物8a在相同条件下。另一方面，在回流下加热7c的MeOH溶液时，发生环化反应，得到相应的1,2,4-三唑-3-硒酮9b。再次，当将4b和6b的混合物在MeOH中加热时，形成相同的产物。令人惊讶的是，在相同条件下，类型5的硒代氨基脲的类似环化反应失败，仅观察到分解。X射线晶体学已经确定了7a，7d和9b的结构。
• Synthesis of 2,3-dihydroimidazo[2,1-b]thiazole derivatives via cyclization of N-allylimidazoline-2-thiones
  作者：Marcin Jasiński、Grzegorz Mlostoń、Heinz Heimgartner

  DOI：10.1002/jhet.469

  日期：2010.11

  subsequent cyclization of the easily available N‐allylimidazoline‐2‐thiones 5, is described. Selected transformations of the iodomethyl derivatives 9, leading to methylidene compounds 10 or the sulfide 11 (Nu = RS), via elimination with a base or via substitution with an enolizable imidazoline‐2‐thione (the term “1,3‐dihydroimidazole‐2‐thione” will be used alternatively), respectively, are presented. J

  描述了一种通过碘化和随后环化容易获得的N-烯丙基咪唑啉-2-硫酮5来制备2,3-二氢咪唑并[ 2,1- b ]噻唑9的新方法。碘甲基衍生物9的选择性转化，通过用碱消除或通过可烯丙基咪唑啉-2-硫酮（术语“ 1,3-二氢咪唑-2”取代）产生亚甲基化合物10或硫化物11（Nu = RS） -thione”将分别出现）。J.杂环化​​学。（2010）。
• Development of <b>VU6019650</b>: A Potent, Highly Selective, and Systemically Active Orthosteric Antagonist of the M₅ Muscarinic Acetylcholine Receptor for the Treatment of Opioid Use Disorder
  作者：Aaron T. Garrison、Douglas L. Orsi、Rory A. Capstick、David Whomble、Jinming Li、Trever R. Carter、Andrew S. Felts、Paige N. Vinson、Alice L. Rodriguez、Allie Han、Krishma Hajari、Hyekyung P. Cho、Laura B. Teal、Madeline G. Ragland、Masoud Ghamari-Langroudi、Michael Bubser、Sichen Chang、Nathalie C. Schnetz-Boutaud、Olivier Boutaud、Anna L. Blobaum、Daniel J. Foster、Colleen M. Niswender、P. Jeffrey Conn、Craig W. Lindsley、Carrie K. Jones、Changho Han

  DOI：10.1021/acs.jmedchem.2c00192

  日期：2022.4.28

  acetylcholine receptor (mAChR) subtype 5 (M5) represents a novel potential target for the treatment of multiple addictive disorders, including opioid use disorder. Through chemical optimization of several functional high-throughput screening hits, VU6019650 (27b) was identified as a novel M5 orthosteric antagonist with high potency (human M5 IC50 = 36 nM), M5 subtype selectivity (>100-fold selectivity against

  毒蕈碱性乙酰胆碱受体 (mAChR) 亚型 5 (M 5 ) 代表了治疗多种成瘾性疾病（包括阿片类药物使用障碍）的新型潜在靶点。通过对几个功能性高通量筛选命中的化学优化，VU6019650 ( 27b ) 被确定为一种新型 M 5正构拮抗剂，具有高效力（人类 M 5 IC 50 = 36 nM）、M 5亚型选择性（对 100 倍以上的选择性） human M 1-4 ) 和在临床前成瘾模型中全身给药的有利物理化学特性。在急性脑切片电生理学研究中，27b阻断了非选择性毒蕈碱激动剂 oxotremorine-M 诱导的腹侧被盖区中脑多巴胺神经元神经元放电率的增加，这是中脑边缘多巴胺能奖励回路的一部分。此外，27b还在不损害一般运动输出的剂量范围内抑制雄性 Sprague-Dawley 大鼠的羟考酮自我给药。
• Reactions of Stable -Chlorosulfanyl Chlorides with CS-Functionalized Compounds
  作者：Agnieszka Majchrzak、Aleksandra Janczak、Grzegorz Mlostoń、Anthony Linden、Heinz Heimgartner

  DOI：10.1002/hlca.200390183

  日期：2003.6

  The smooth reaction of 3-chloro-3-(chlorosulfanyl)-2,2,4,4-tetramethylcyclobutanone (3) with 3,4,5-trisubstituted 2,3-dihydro-1H-imidazole-2-thiones 8 and 2-thiouracil (10) in CH2Cl2/Et3N at room temperature yielded the corresponding disulfanes 9 and 11 (Scheme 2), respectively, via a nucleophilic substitution of Cl− of the sulfanyl chloride by the S-atom of the heterocyclic thione. The analogous reaction

  3-氯-3-（氯硫烷基）-2,2,4,4-四甲基环丁酮（3）与3,4,5-三取代的2,3-二氢-1 H-咪唑-2-硫酮8和2-硫尿嘧啶（10）在CH 2氯2 / ET 3 ñ在室温下得到相应的disulfanes 9和11（方案2），分别通过氯的亲核取代-通过的所述S-原子的硫烷基氯化杂环硫酮。3-环己基-2,3-二氢-4,5-二苯基-1H-咪唑-2-硫酮的类似反应（8b）与10与氯二硫烷基衍生物16分别产生相应的三硫烷17和18（方案4）。另一方面，3和4,4-二甲基-2-苯基-1,3-噻唑-5（4 H）-硫酮（12）在CH 2 Cl 2中的反应仅得到4,4-二甲基-2 -苯基-1,3-噻唑-5（4 H）-one（13）和三硫原酸酯衍生物14（一种双二硫烷），收率低（方案3）。在-78°时只有双（1-氯-2,2,4,4-四甲基-3-氧代环丁基）聚硫醚15形成了。即使在-78°，CH 2 Cl