3-cyclohexyl-2-mercapto-5-phenyl-3H-thieno[2,3-d]pyrimidin-4-one | 851852-86-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 3-cyclohexyl-2-mercapto-5-phenyl-3H-thieno[2,3-d]pyrimidin-4-one
• 英文别名: 3-cyclohexyl-5-phenyl-2-sulfanyl-3H,4H-thieno[2,3-d]pyrimidin-4-one；3-cyclohexyl-5-phenyl-2-sulfanylidene-1H-thieno[2,3-d]pyrimidin-4-one
• CAS: 851852-86-3
• 化学式: C₁₈H₁₈N₂OS₂
• mdl: MFCD06660486
• 分子量: 342.486
• InChiKey: NGKCASJUMUKMJU-UHFFFAOYSA-N

物化性质

• 沸点：
  503.7±52.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  92.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-cyclohexyl-2-mercapto-5-phenyl-3H-thieno[2,3-d]pyrimidin-4-one 在 potassium carbonate 、 肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (3-cyclohexyl-4-oxo-5-phenyl-3,4-dihydrothieno[2,3-d]pyrimidin-2-ylsulfanyl)acetic acid hydrazide
  参考文献：
  名称：

  Structure–activity relationship study of novel tissue transglutaminase inhibitors

  摘要：

  Thieno[2,3-d]pyrimidin-4-one acylhydrazide derivatives were discovered as moderately potent inhibitors of TGase 2 (tissue transglutaminase) utilizing a fluorescence-based assay that measured TGase 2 catalyzed incorporation of the dansylated Lys derivative alpha-N-Boc-Lys-CH2-CH2-dansyl into the protein substrate N,N-dimethylated-casein. A SAR study revealed that the acylhydrazide thioether side-chain and the thiophene ring were critical to inhibitory activity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.02.005
• 作为产物：
  描述：

  2-氨基-4-苯基噻吩-3-羧酸乙酯 在 吡啶 、 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 3-cyclohexyl-2-mercapto-5-phenyl-3H-thieno[2,3-d]pyrimidin-4-one
  参考文献：
  名称：

  Structure–activity relationship study of novel tissue transglutaminase inhibitors

  摘要：

  Thieno[2,3-d]pyrimidin-4-one acylhydrazide derivatives were discovered as moderately potent inhibitors of TGase 2 (tissue transglutaminase) utilizing a fluorescence-based assay that measured TGase 2 catalyzed incorporation of the dansylated Lys derivative alpha-N-Boc-Lys-CH2-CH2-dansyl into the protein substrate N,N-dimethylated-casein. A SAR study revealed that the acylhydrazide thioether side-chain and the thiophene ring were critical to inhibitory activity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.02.005

文献信息

• 2-(3,4-Dihydro-4-Oxothieno[2,3-d]pyrimidin-2-ylthio) Acetamides as a New Class of Falcipain-2 Inhibitors. 3. Design, Synthesis and Biological Evaluation
  作者：Jin Zhu、Tong Chen、Jie Liu、Ruoqun Ma、Weiqiang Lu、Jin Huang、Honglin Li、Jian Li、Hualiang Jiang

  DOI：10.3390/molecules14020785

  日期：——

  The cysteine protease falcipain-2 (FP-2) of Plasmodium falciparum is a principal cysteine protease and an essential hemoglobinase of erythrocytic P. falciparum trophozoites, making it become an attractive target enzyme for developing anti-malarial drugs. In this study, a series of novel small molecule FP-2 inhibitors have been designed and synthesized based on compound 1, which was identified by using structure-based virtual screening in conjunction with an enzyme inhibition assay. All compounds showed high inhibitory effect against FP-2 with IC50s of 1.46-11.38 μM, and the inhibitory activity of compound 2a was ~2 times greater than that of prototype compound 1. The preliminary SARs are summarized and should be helpful for future inhibitor design, and the novel scaffold presented here, with its potent inhibitory activity against FP-2, also has potential application in discovery of new anti-malarial drugs.

  恶性疟原虫 (Plasmodium falciparum) 半胱氨酸蛋白酶 (falcipain-2， FP-2) 是原生质型疟原虫的主要半胱氨酸蛋白酶和必须的血红蛋白酶，这使得它成为研制抗疟药物的一个有吸引力的靶标酶。在本研究中，我们基于用酶抑制法结合基于结构的虚拟筛选得到的化合物 1，设计并合成了系列新型小分子 FP-2 抑制剂。所有化合物均为 FP-2的高效抑制剂，其半抑制浓度 (IC50) 值范围为 1.46 至 11.38 μM，化合物 2a 的抑制活性是母体化合物 1 的 2倍左右。本研究概括总结的初步构效关系将有助于未来抑制剂的设计，这里展示的新骨架以其对 FP-2的强效抑制活性，在发现新型抗疟药物方面也具有潜在的应用价值。
• Tissue transglutaminase inhibitors
  申请人：Stein L. Ross

  公开号：US20060183759A1

  公开（公告）日：2006-08-17

  The present invention provides novel compounds and methods useful for treating transglutaminase associated disorders such as celiac spru, Alzheimer's disease and Huntington's disease. Certain compounds of the invention are tissue transglutaminase inhibitors that comprise thiophene moieties. Methods of the invention include treatment of transglutaminase associated disorders with inhibitors of transglutaminase.

  本发明提供了一种治疗转酰胺酶相关疾病的新化合物和方法，例如腹泻性脆皮病、阿尔茨海默病和亨廷顿病。本发明的某些化合物是组织转酰胺酶抑制剂，包括噻吩基团。本发明的方法包括使用转酰胺酶抑制剂治疗转酰胺酶相关疾病。
• [EN] SUBSTITUED 3,4-DIHYDROTHIENO [2,3-D] PYRMIDINES AS TISSUE TRANSGLUTAMINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA TRANSGLUTAMINASE TISSULAIRE
  申请人：BRIGHAM & WOMENS HOSPITAL

  公开号：WO2006060702A1

  公开（公告）日：2006-06-08

  [EN] The present invention provides novel compounds and methods useful for treating transglutaminase associated disorders such as celiac spru, Alzheimer's disease and Huntington's disease. Certain compounds of the invention are tissue transglutaminase inhibitors that comprise thiophene moieties. Methods of the invention include treatment of transglutaminase associated disorders with inhibitors of transglutaminase.
  [FR] L'invention concerne de nouveaux composés et méthodes permettant de traiter des troubles associés à la transglutaminase, tels que la maladie coeliaque, la maladie d'Alzheimer et la maladie de Huntington. Certains composés selon l'invention possèdent des inhibiteurs de la transglutaminase tissulaire qui comprennent des fractions thiophène. Des méthodes selon l'invention comprennent le traitement des troubles associés à la transglutaminase à l'aide des inhibiteurs de la transglutaminase.
• Structure–activity relationship study of novel tissue transglutaminase inhibitors
  作者：Eric Duval、April Case、Ross L. Stein、Gregory D. Cuny

  DOI：10.1016/j.bmcl.2005.02.005

  日期：2005.4

  Thieno[2,3-d]pyrimidin-4-one acylhydrazide derivatives were discovered as moderately potent inhibitors of TGase 2 (tissue transglutaminase) utilizing a fluorescence-based assay that measured TGase 2 catalyzed incorporation of the dansylated Lys derivative alpha-N-Boc-Lys-CH2-CH2-dansyl into the protein substrate N,N-dimethylated-casein. A SAR study revealed that the acylhydrazide thioether side-chain and the thiophene ring were critical to inhibitory activity. (c) 2005 Elsevier Ltd. All rights reserved.