3-丙烯基-2-巯基-3,4,5,6,7,8-六氢化苯并[4,5]噻吩并[2,3-B]吡啶-4-酮 | 42062-91-9

• 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
• 中文名称: 3-丙烯基-2-巯基-3,4,5,6,7,8-六氢化苯并[4,5]噻吩并[2,3-B]吡啶-4-酮
• 中文别名: 3-烯丙基-2-疏基-5,6,7,8-四氢-3H-苯并[4,5]噻吩并[3,2-d]嘧啶-4-酮
• 英文名称: 3-allyl-2-thioxo-2,3,5,6,7,8-hexahydro-1H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one
• 英文别名: 3-(prop-2-en-1-yl)-2-thioxo-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-one；3-Allyl-4,5,6,7-tetrahydro-benzothiopheno<3,2-e>-3,4H-pyrimidin-4-on-2-thiol；3-prop-2-enyl-2-sulfanylidene-5,6,7,8-tetrahydro-1H-[1]benzothiolo[2,3-d]pyrimidin-4-one
• CAS: 42062-91-9
• 化学式: C₁₃H₁₄N₂OS₂
• mdl: MFCD00484392
• 分子量: 278.399
• InChiKey: ZDHGJHRONIXYAM-UHFFFAOYSA-N

物化性质

• 熔点：
  228-230℃
• 沸点：
  467.2±55.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)
• 溶解度：
  14.7 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.384
• 拓扑面积：
  92.7
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  3-丙烯基-2-巯基-3,4,5,6,7,8-六氢化苯并[4,5]噻吩并[2,3-B]吡啶-4-酮 在 吗啉 作用下， 生成 2-methylene-2,3,6,7,8,9-hexahydrobenzo[b]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidin-5-one
  参考文献：
  名称：

  Synthese von 2-Methylen-2,3-dihydro- und 2-Methyl-5H-thiazolo[3,2—a]thieno[2,3—d]pyrimidinen

  摘要：

  DOI：

  10.1007/bf00912986
• 作为产物：
  描述：

  ethyl 2-(3-allylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 在 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以85%的产率得到3-丙烯基-2-巯基-3,4,5,6,7,8-六氢化苯并[4,5]噻吩并[2,3-B]吡啶-4-酮
  参考文献：
  名称：

  以噻吩并入硫脲基取代基为前体的新型杂环化合物的合成及体外抗癌活性

  摘要：

  2-（3-烯丙基硫脲基）-4,5,6,7-四氢苯并[b]噻吩-3-羧酸乙酯（1）被用作合成新杂环的基础。通过化合物1与各种试剂如氯乙酸，二酰丙二酸酯，茚三酮，2，3-环氧-2，3-二氢-1，4-萘醌和水合肼缩合，获得嘧啶和噻唑部分。使用光谱测量证实了新合成的化合物的结构。评价制备的产物对结肠HCT-116人癌细胞系的抗癌活性。化合物6、9、10a，11、12、15显示出有效的活性。

  DOI：

  10.17344/acsi.2019.5571

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。
• Heterocyclization of 5,6-disubstituted 3-alkenyl-2-thioxothieno[2,3-<i>d</i>]pyrimidin-4-one with <i>p</i>-alkoxyphenyltellurium trichloride
  作者：Mykola Kut、Mikhajlo Onysko、Vasyl Lendel

  DOI：10.1515/hc-2016-0169

  日期：2016.12.1

  Abstract Electrophilic heterocyclization of 5,6-disubstituted 3-alkenyl-2-thioxothieno[2,3-d]pyrimidin-4-ones by treatment with p-alkoxyphenyltellurium trichlorides leads to annulation of the thiazoline moiety with the formation of 6,7-disubstituted-2-[dichloro-(p-alkoxyphenyl)telluromethyl]-2,3-dihydro-5Н-[1,3]thiazolo[3,2-а]thieno[2,3-d]pyrimidin-5-one hydrochlorides.

  摘要 5,6-二取代的 3-烯基-2-硫代噻吩并[2,3-d]嘧啶-4-酮通过对-烷氧基苯基三氯化物处理的亲电杂环化导致噻唑啉部分的环化，形成6,7-二取代-2-[二氯-(对烷氧基苯基)碲甲基]-2,3-二氢-5Н-[1,3]噻唑并[3,2-а]噻吩并[2,3-d]嘧啶-5-酮盐酸盐.
• Compounds and methods for inhibition of hedgehog signaling and phosphodiesterase
  申请人：Vanderbilt University

  公开号：US10329304B2

  公开（公告）日：2019-06-25

  Compounds and compositions, and methods of use thereof, are provided and have utility in inhibiting hedgehog signaling and/or phosphodiesterase-4 activity.

  所提供的化合物和组合物及其使用方法可用于抑制刺猬信号和/或磷酸二酯酶-4 的活性。
• Development of thieno- and benzopyrimidinone inhibitors of the Hedgehog signaling pathway reveals PDE4-dependent and PDE4-independent mechanisms of action
  作者：Jonathan E. Hempel、Adrian G. Cadar、Charles C. Hong

  DOI：10.1016/j.bmcl.2016.03.013

  日期：2016.4

  From a high content in vivo screen for modulators of developmental patterning in embryonic zebrafish, we previously identified eggmanone (EGM1, 3) as a Hedgehog (Hh) signaling inhibitor functioning downstream of Smoothened. Phenotypic optimization studies for in vitro probe development utilizing a Gli transcription-linked stable luciferase reporter cell line identified EGM1 analogs with improved potency and aqueous solubility. Mechanistic profiling of optimized analogs indicated two distinct scaffold clusters: PDE4 inhibitors able to inhibit downstream of Sufu, and PDE4-independent Hh inhibitors functioning between Smo and Sufu. Each class represents valuable in vitro probes for elucidating the complex mechanisms of Hh regulation. Published by Elsevier Ltd.
• A Facile Microwave-Assisted Synthesis of Some Fused Pyrimidine Derivatives
  作者：S. A. Al Issa

  DOI：10.13005/ojc/300209

  日期：2014.7.1