5-isothiocyanato-3-methyl-2,4-thiophenedicarboxylic acid diethyl ester | 304898-01-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 5-isothiocyanato-3-methyl-2,4-thiophenedicarboxylic acid diethyl ester
• 英文别名: Diethyl 5-isothiocyanato-3-methylthiophene-2,4-dicarboxylate
• CAS: 304898-01-9
• 化学式: C₁₂H₁₃NO₄S₂
• mdl: MFCD09971940
• 分子量: 299.372
• InChiKey: DLEAQPYSIISVIY-UHFFFAOYSA-N

物化性质

• 沸点：
  443.9±45.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  125
• 氢给体数：
  0
• 氢受体数：
  7

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  5-isothiocyanato-3-methyl-2,4-thiophenedicarboxylic acid diethyl ester 在 一水合肼 、 三乙胺 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 14.0h， 生成 3-amino-5-methyl-4-oxo-2-hydrazino-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-6-yl hydrazide
  参考文献：
  名称：

  新型和选择性的5-HT3和5-HT4受体配体的设计，合成和结合特性。

  摘要：

  这项工作报告了新的噻吩并嘧啶并哌嗪和哌嗪基糖基氨基二甲基噻吩衍生物的5-HT3和5-HT4受体的合成和结合试验，以便确定每种受体的有效和选择性配体。3-氨基-2-（4-苄基-1-哌嗪基）-5,6-二甲基-噻吩并[2,3-d]嘧啶-4（3H）-一衍生物28对5的亲和力和选择性最高-HT3超过5-HT4受体（5-HT3 Ki = 3.92 nM，5-HT4无效），而2- [4- [4-（2-嘧啶基）-1-哌嗪基]丁酰基氨基] -4,5 -5-二甲基-3-噻吩羧酸乙酯（41）对5-HT4的亲和力和选择性高于5-HT3受体（5-HT4 Ki = 81.3 nM，5-HT3不活泼）。以化合物41为模板，对哌嗪基糖基氨基二甲基噻吩系列（39-42）的化合物进行构象分析。

  DOI：

  10.1016/s0223-5234(01)01216-8
• 作为产物：
  描述：

  2-氨-4-甲基噻吩-3,5-二羧酸二乙酯 、 硫光气 在 碳酸氢钠 作用下， 以 氯仿 、 水 为溶剂， 反应 1.3h， 以40%的产率得到5-isothiocyanato-3-methyl-2,4-thiophenedicarboxylic acid diethyl ester
  参考文献：
  名称：

  High affinity and selectivity of [[(arylpiperazinyl)alkyl]thio]thieno[2,3-d]pyrimidinone derivatives for the 5-HT1A receptor.Synthesis and structure–affinity relationships

  摘要：

  In this work we report the affinity of new thienopyrimidinones for 5-HT(1A)Rs and the selectivity versus alpha(1)ARs. The 3-amino-2-[[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]thio]-6-ethyl-thieno[2,3-d]pyrimidin-4(3H)-one 27 is the most potent and selective (Ki 0.19 nM, selectivity 115). Compound 31 with the N4 piperazine orthonitrophenyl nucleus instead of the orthomethoxyphenyl also shows a good affinity and selectivity (Ki 1.46 nM, selectivity 84). The results of derivatives 28, 29 and 30 (Ki 3.28, 12.59 and 4.38 nM; selectivity 24, 4 and 5, respectively), which have, respectively, an ethyl, an allyl and an acetylamino group instead of an N3 amino group, indicate the importance of this last group for the interaction with 5-HT1AR. Comparison of the results for the superior homologue 53 (Ki 3.72 nM, selectivity 51) and the inferior homologue 52 (5-HT1A Ki 1 499 nM, alpha(1)A Ki NA) of 2-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-6,7-dimethyl-8H-[1,3,4]thiadiazolo[3,2-a]thieno[2,3-d]pyrimidin-8-one 57 (Ki 23 nM, selectivity 5) shows how important the length of the chain binding the two heterocyclic systems is in the interaction with 5-HT(1A)Rs and alpha(1)ARs. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00175-6

文献信息

• Alchemical Design of Pharmacological Chaperones with Higher Affinity for Phenylalanine Hydroxylase
  作者：María Conde-Giménez、Juan José Galano-Frutos、María Galiana-Cameo、Alejandro Mahía、Bruno L. Victor、Sandra Salillas、Adrián Velázquez-Campoy、Rui M. M. Brito、José Antonio Gálvez、María D. Díaz-de-Villegas、Javier Sancho

  DOI：10.3390/ijms23094502

  日期：——

  pharmacological chaperones to treat PKU, a lead compound was discovered (compound IV) that exhibited promising in vitro and in vivo chaperoning activity on PAH. The structure of the PAH-IV complex has been reported. Here, using alchemical free energy calculations (AFEC) on the structure of the PAH-IV complex, we design a new generation of compound IV-analogues with a higher affinity for the enzyme. Seventeen

  苯丙酮尿症 (PKU) 是一种罕见的代谢疾病，由编码苯丙氨酸羟化酶 (PAH) 和将必需氨基酸苯丙氨酸转化为酪氨酸的酶的人类基因 PAH 的变异引起。许多引起 PKU 的变异会损害编码酶的构象稳定性，降低或消除其催化活性，并导致血液中苯丙氨酸浓度升高，这是神经毒性的。已经开发了几种治疗方法来治疗更严重的疾病表现，但它们要么不完全有效，要么难以终生坚持。在寻找治疗 PKU 的新型药理学伴侣时，发现了一种先导化合物（化合物 IV），该化合物在体外和体内对 PAH 具有良好的伴侣活性。PAH-IV 复合物的结构已有报道。在这里，我们对 PAH-IV 复合物的结构使用炼金术自由能计算 (AFEC)，设计了对酶具有更高亲和力的新一代化合物 IV 类似物。合成了 17 种新型类似物，并进行了热位移和等温滴定量热法 (ITC) 测定，以实验评估它们的稳定效果和对酶的亲和力。大多数新衍生物与 PAH 的结合比先导化合物
• Design, synthesis and binding properties of novel and selective 5-HT3 and 5-HT4 receptor ligands
  作者：Maria Modica、Maria Santagati、Salvatore Guccione、Filippo Russo、Alfredo Cagnotto、Mara Goegan、Tiziana Mennini

  DOI：10.1016/s0223-5234(01)01216-8

  日期：2001.3

  the 5-HT3 and 5-HT4 receptors of new thienopyrimidopiperazine and piperazinylacylaminodimethylthiophene derivatives, in order to identify potent and selective ligands for each receptor. The 3-amino-2-(4-benzyl-1-piperazinyl)-5,6-dimethyl-thieno[2,3-d]pyrimidin-4(3H)-one derivative 28 showed the highest affinity and selectivity for the 5-HT3 over the 5-HT4 receptor (5-HT3 Ki=3.92 nM, 5-HT4 not active)

  这项工作报告了新的噻吩并嘧啶并哌嗪和哌嗪基糖基氨基二甲基噻吩衍生物的5-HT3和5-HT4受体的合成和结合试验，以便确定每种受体的有效和选择性配体。3-氨基-2-（4-苄基-1-哌嗪基）-5,6-二甲基-噻吩并[2,3-d]嘧啶-4（3H）-一衍生物28对5的亲和力和选择性最高-HT3超过5-HT4受体（5-HT3 Ki = 3.92 nM，5-HT4无效），而2- [4- [4-（2-嘧啶基）-1-哌嗪基]丁酰基氨基] -4,5 -5-二甲基-3-噻吩羧酸乙酯（41）对5-HT4的亲和力和选择性高于5-HT3受体（5-HT4 Ki = 81.3 nM，5-HT3不活泼）。以化合物41为模板，对哌嗪基糖基氨基二甲基噻吩系列（39-42）的化合物进行构象分析。
• The Utility of Isothiocyanato Thiophenes in the Synthesis of Thieno[2,3-<i>d</i>]pyrimidine Derivatives as Possible Radioprotective and Anticancer Agents
  作者：M. M. Ghorab、A. N. Osman、E. Noaman、H. I. Heiba、N. H. Zaher

  DOI：10.1080/10426500500544238

  日期：2006.9.1

  The synthesis of novel thioureido derivatives 3, 8, and 10; biscompounds 7, 9, and 11; and tetracyclic compounds 5, 6, and 16 utilizing 5-isothiocyanato-3-methyl-thiophene-2,4-dicarboxylic acid diethyl ester 2 are reported. The structures of these compounds were confirmed by microanalyses and IR, H-1 NMR, and mass spectroscopy. Preliminary biological studies of some of the synthesized compounds showed promising radioprotective and anticancer activities.
• High affinity and selectivity of [[(arylpiperazinyl)alkyl]thio]thieno[2,3-d]pyrimidinone derivatives for the 5-HT1A receptor.Synthesis and structure–affinity relationships
  作者：Maria Modica、Maria Santagati、Filippo Russo、Carlo Selvaggini、Alfredo Cagnotto、Tiziana Mennini

  DOI：10.1016/s0223-5234(00)00175-6

  日期：2000.8

  In this work we report the affinity of new thienopyrimidinones for 5-HT(1A)Rs and the selectivity versus alpha(1)ARs. The 3-amino-2-[[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]thio]-6-ethyl-thieno[2,3-d]pyrimidin-4(3H)-one 27 is the most potent and selective (Ki 0.19 nM, selectivity 115). Compound 31 with the N4 piperazine orthonitrophenyl nucleus instead of the orthomethoxyphenyl also shows a good affinity and selectivity (Ki 1.46 nM, selectivity 84). The results of derivatives 28, 29 and 30 (Ki 3.28, 12.59 and 4.38 nM; selectivity 24, 4 and 5, respectively), which have, respectively, an ethyl, an allyl and an acetylamino group instead of an N3 amino group, indicate the importance of this last group for the interaction with 5-HT1AR. Comparison of the results for the superior homologue 53 (Ki 3.72 nM, selectivity 51) and the inferior homologue 52 (5-HT1A Ki 1 499 nM, alpha(1)A Ki NA) of 2-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-6,7-dimethyl-8H-[1,3,4]thiadiazolo[3,2-a]thieno[2,3-d]pyrimidin-8-one 57 (Ki 23 nM, selectivity 5) shows how important the length of the chain binding the two heterocyclic systems is in the interaction with 5-HT(1A)Rs and alpha(1)ARs. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
• The Synthesis of Some New Sulfur Heterocyclic Compounds as Potential Radioprotective and Anticancer Agents
  作者：M. M. Ghorab、A. N. Osman、E. Noaman、H. I. Heiba、N. H. Zaher

  DOI：10.1080/10426500500544014

  日期：2006.8.1

  reagents. The identification of the new compounds was established by elemental analysis, and IR, 1H NMR, and mass spectral data. Some prepared compounds were tested for their radioprotective and anticancer activities. Compounds 7 and 16 showed significant activities against EAC cells, while compound 5 exhibited radioprotective activity.

  一些新型 5-取代氨基-3-甲基噻吩-2,4-二羧酸二乙酯 (3-6), 3,5-二甲基-4-氧代-2-硫代-1,2,3,4-四氢-噻吩并 [2,3-d] 嘧啶 (7)、咪唑并噻吩并嘧啶 (8) 和 1,2,4-三唑并噻吩并嘧啶 (11) 通过异硫氰酸酯 2 与不同试剂的反应合成。新化合物的鉴定是通过元素分析、IR、1H NMR 和质谱数据确定的。测试了一些制备的化合物的辐射防护和抗癌活性。化合物 7 和 16 显示出显着的抗 EAC 细胞活性，而化合物 5 显示出辐射防护活性。