乙基2,5-二氢-5-氧代-1-苯基-1H-1,2,4-噻唑-3-羧酸 | 67267-08-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 乙基2,5-二氢-5-氧代-1-苯基-1H-1,2,4-噻唑-3-羧酸
• 英文名称: ethyl 1-phenyl-5-oxo-1,2,4-triazole-3-carboxylate
• 英文别名: Ethyl 5-oxo-1-phenyl-2,5-dihydro-1H-1,2,4-triazole-3-carboxylate；ethyl 5-oxo-1-phenyl-4H-1,2,4-triazole-3-carboxylate
• CAS: 67267-08-7
• 化学式: C₁₁H₁₁N₃O₃
• mdl: MFCD09877889
• 分子量: 233.227
• InChiKey: DFWQCUMZCKRJKD-UHFFFAOYSA-N

物化性质

• 熔点：
  193-194 °C(Solv: ethanol (64-17-5))
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  71
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  乙基2,5-二氢-5-氧代-1-苯基-1H-1,2,4-噻唑-3-羧酸 在 ammonium acetate 、 氨 、 potassium carbonate 、 三氯氧磷 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 23.33h， 生成 4-(8-amino-3-oxo-2-phenyl-2,3-dihydro-1,2,4-triazolo [4,3-a]pyrazin-6-yl)benzensolfonamide
  参考文献：
  名称：

  发现了一流的多靶腺苷A2A受体拮抗剂-碳酸酐酶IX和XII抑制剂。8-氨基-6-芳基-2-苯基-1,2,4-三唑并[4,3-a]吡嗪-3-酮衍生物是新的潜在抗肿瘤药。

  摘要：

  本文介绍了鉴定作为多种潜在抗肿瘤药物的一流的多靶腺苷A 2A受体拮抗剂-碳酸酐酶（CA）IX和XII抑制剂。为了获得多作用配体，将有效的腺苷hA 2A受体（AR）拮抗剂8-氨基-2,6-二苯基三唑并[4,3-a]吡嗪-3-one作为主要化合物。为了解决针对肿瘤相关的CA同工型的活性，通过在6-苯基环上或通过不同间隔基连接到前者的苯基侧基上引入不同的取代基（OH，COOH，CONHOH，SO 2 NH 2）进行修饰。在新的triazolopyrazines 1 - 23，最活跃的是具有磺酰胺残基的那些。衍生物20的特征是在6苯基环的对位通过CONH（CH 2）2 CONH间隔基连接的4-磺酰胺基苯基残基，显示了在三个靶点上活性的最佳组合。实际上，它以纳摩尔浓度（K i  = 5.0和27.0 nM）抑制了肿瘤相关的hCA IX和XII同工酶，并且对hA 2A AR（K i  = 108 nM

  DOI：

  10.1016/j.ejmech.2020.112478
• 作为产物：
  描述：

  ethyl (phenylhydrazono)chloroacetate 在 氨 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 4.0h， 生成 乙基2,5-二氢-5-氧代-1-苯基-1H-1,2,4-噻唑-3-羧酸
  参考文献：
  名称：

  The 1,2,4-Triazolo[4,3-a]pyrazin-3-one as a Versatile Scaffold for the Design of Potent Adenosine Human Receptor Antagonists. Structural Investigations to Target the A_2A Receptor Subtype

  摘要：

  In this work, we describe the identification of the 1,2,4-triazolo[4,3-a]pyrazin-3-one as a new versatile scaffold for the development of adenosine human (h) receptor antagonists. The new chemotype ensued from a molecular simplification approach applied to our previously reported 1,2,4-triazolo[4,3-a]quinoxalin-1-one series. Hence, a set of novel 8-amino-2-aryl-1,2,4-triazolopyrazin-3-one derivatives, featured by different substituents on the 2-phenyl ring (R) and at position 6 (R-6), was synthesized with the main purpose of targeting the hA(2A) adenosine receptor (AR). Several compounds possessed nanomolar affinity for the hA(2A) AR (K-i = 2.910 nM) and some, very interestingly, also showed high selectivity for the target. One selected potent hA(2A) AR antagonist (12, R = H, R-6 = 4-methoxyphenyl) demonstrated some ability to counteract MPP+-induced neurotoxicity in cultured human neuroblastoma SH-SY5Y cells, a widely used in vitro Parkinsons disease model. Docking studies at hAR structures were performed to rationalize the observed affinity data.

  DOI：

  10.1021/acs.jmedchem.7b00457

文献信息

• Monoacylglycerol Lipase Modulators
  申请人：Janssen Pharmaceutica NV

  公开号：US20200102311A1

  公开（公告）日：2020-04-02

  Bridged compounds of Formula (I) and Formula (II), pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with MGL modulation, such as those associated with pain, psychiatric disorders, neurological disorders (including, but not limited to major depressive disorder, treatment resistant depression, anxious depression, bipolar disorder), cancers and eye conditions. wherein R 2 , R 3 R 4 , R 5 and R 6 are defined herein.

  桥接化合物，其结构式为(I)和(II)，包含它们的药物组合物，制造它们的方法，以及使用它们的方法，包括用于治疗与MGL调节相关的疾病状态、障碍和状况的方法，如与疼痛、精神障碍、神经障碍（包括但不限于重性抑郁障碍、难治性抑郁、焦虑性抑郁、双相情感障碍）、癌症和眼科疾病相关的方法。 其中R2、R3、R4、R5和R6的定义如下。
• A New Method for the Synthesis of 1-Aryl-1,2,4-triazole Derivatives
  作者：Mykola Obushak、Vasyl Matiychuk、Mykhaylo Potopnyk、Roman Luboradzki

  DOI：10.1055/s-0030-1260026

  日期：2011.6

  A new and convenient one-step recyclization method for the synthesis of ethyl 1-aryl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-3-carboxylates is reported. Various ethyl chloro(2-arylhydrazinylidene)ethanoates react with thiazolidine-2,4-dione in the presence of potassium hydroxide to produce the 1-aryl-1,2,4-triazole derivatives in moderate to good yields. The procedure is economical, environmentally friendly

  报道了一种新的方便的一步回收方法，用于合成1-芳基-5-氧代-4，5-二氢-1 H -1,2,4-三唑-3-羧酸乙酯。在氢氧化钾存在下，各种氯（2-芳基肼基亚乙基）乙基乙酯与噻唑烷-2,4-二酮反应，以中等至良好的产率产生1-芳基-1,2,4-三唑衍生物。该程序经济，环保且易于执行。 1,2,4-三唑-重氮盐-开环-噻唑烷-2,4-二酮-杂环化
• Novel 8-amino-1,2,4-triazolo[4,3-a]pyrazin-3-one derivatives as potent human adenosine A1 and A2A receptor antagonists. Evaluation of their protective effect against β-amyloid-induced neurotoxicity in SH-SY5Y cells
  作者：Matteo Falsini、Daniela Catarzi、Flavia Varano、Diego Dal Ben、Gabriella Marucci、Michela Buccioni、Rosaria Volpini、Lorenzo Di Cesare Mannelli、Carla Ghelardini、Vittoria Colotta

  DOI：10.1016/j.bioorg.2019.03.046

  日期：2019.6

  In this work, an enlarged series of 1,2,4-triazolo [4,3-a] pyrazin-3-ones was designed to target the human (h) A(2A) adenosine receptor (AR) or both h(A1) and hA(2A) ARs. The novel 8-amino-1,2,4-triazolopyrazin-3-one derivatives 1-25 featured a phenyl or a benzyl pendant at position 2 while different aryl/heteroaryl substituents were placed at position 6. Two compounds (8 and 10) endowed with high affinity (K-i = 7.2 and 10.6 nM) and a complete selectivity for the hA(2A) AR were identified. Moreover, several derivatives possessed nanomolar affinity for both hA(1) and hA(2A) ARs (both K-i < 20 nM) and different degrees of selectivity versus the hA(3) AR. Two selected compounds (10 and 25) demonstrated ability in preventing beta-amyloid peptide (25-35)-induced neurotoxicity in SH-SY5Y cells. Results of docking studies at the hA(2A) and hA(1) AR crystal structures helped us to rationalize the observed affinity data and to highlight that the steric hindrance of the substituents at the 2- and 6-position of the bicyclic core affects the binding mode in the receptor cavity.
• Antioxidant-Conjugated 1,2,4-Triazolo[4,3-<i>a</i>]pyrazin-3-one Derivatives: Highly Potent and Selective Human A_2A Adenosine Receptor Antagonists Possessing Protective Efficacy in Neuropathic Pain
  作者：Matteo Falsini、Daniela Catarzi、Flavia Varano、Costanza Ceni、Diego Dal Ben、Gabriella Marucci、Michela Buccioni、Rosaria Volpini、Lorenzo Di Cesare Mannelli、Elena Lucarini、Carla Ghelardini、Gianluca Bartolucci、Marta Menicatti、Vittoria Colotta

  DOI：10.1021/acs.jmedchem.9b00778

  日期：2019.9.26

  New 8-amino-6-aryl-1,2,4-triazolo[4,3-a]pyrazin-3-ones were designed to obtain dual antioxidant-human A(2A) adenosine receptor (hA(2A) AR) antagonists. Two sets of compounds were synthesized, the first featuring phenol rings at the 6-position, the second bearing the lipoyl and 4-hydroxy-3,5-di-tertbut-benzoyl residues appended by different linkers on the 6-phenyl ring. Several new triazolopyrazines (1-21) were potent and selective hA(2A) AR antagonists (K-i = 0.17-54.5 nM). Compounds 11, 15, and 21, featuring antioxidant moieties, and compound 12, lacking the antioxidant functionality, reduced oxaliplatin-induced toxicity in microglia cells, the most active being the lipoyl-derivative 15 and the (4-hydroxy-3,5-di-tertbutyl)benzoyl-analogue 21 which were effective in reducing the oxygen free radical level. The lipoyl-derivative 15 was also able to revert oxaliplatin-induced neuropathy in the mouse. In vivo efficacy of 15 makes it a promising neuroprotective agent in oxidative stress-related diseases.
• JUST, M.;BODE, H. -J.
  作者：JUST, M.、BODE, H. -J.

  DOI：——

  日期：——