4-(3-chlorophenyl)-6-methyl-N-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide | 397848-68-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(3-chlorophenyl)-6-methyl-N-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
• 英文别名: N-phenyl-4-(3-chlorophenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide；4-(3-chlorophenyl)-6-methyl-N-phenyl-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carboxamide
• CAS: 397848-68-9
• 化学式: C₁₈H₁₆ClN₃OS
• 分子量: 357.864
• InChiKey: CDFMWTXKNUDLTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  85.2
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(Biphenyl-4-ylmethyl)indol-3-carbaldehyde 、 4-(3-chlorophenyl)-6-methyl-N-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide 在 sodium acetate 、 乙酸酐 、 溶剂黄146 、 氯乙酸 作用下， 反应 24.0h， 以55%的产率得到(Z)-2-((1-(biphenyl-4-yl)indol-3-yl)methylene)-5-(3-chlorophenyl)-7-methyl-3-oxo-N-phenylthiazolo[3,2-a]pyrimidine-6-carboxamide
  参考文献：
  名称：

  噻唑并[3,2-a]嘧啶酮衍生物作为Bcl-2家族蛋白的一般抑制剂的发现和开发

  摘要：

  一类具有常见的噻唑并[3,2- a ]嘧啶酮基序的化合物已被开发为Bcl-2家族蛋白的一般抑制剂。最初使用基于荧光偏振的竞争结合测定法对小型化合物库进行随机筛选来鉴定先导化合物。15 N-HSQC NMR实验进一步证实了其与Bcl-x L蛋白的结合。分子模型研究的结果指导了对先导化合物的结构修饰。与先导化合物相比，在获得的42种化合物中，许多化合物与Bcl-2家族蛋白的结合亲和力大大提高。最有效的化合物BCL‐LZH‐ 40抑制BH3肽与Bcl‐x L的结合和Bcl-2和Mcl-1的与抑制常数（ķ我）的17，534和200N的中号，分别。

  DOI：

  10.1002/cmdc.201000484
• 作为产物：
  描述：

  苯胺 以 乙醇 、 甲苯 为溶剂， 生成 4-(3-chlorophenyl)-6-methyl-N-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide
  参考文献：
  名称：

  Targeting Dormant Tuberculosis Bacilli: Results for Molecules with a Novel Pyrimidone Scaffold

  摘要：

  Our inability to completely control TB has been due in part to the presence of dormant mycobacteria. This also renders drug regimens ineffective and is the prime cause of the appearance of drug‐resistant strains. In continuation of our efforts to develop novel antitubercular agents that especially target dormant mycobacteria, a set of 55 new compounds belonging to the pyrimidone class were designed on the basis of CoMFA and CoMSIA studies, and these were synthesized and subsequently tested against both the dormant and virulent BCG strain of M. tuberculosis. Some novel compounds have been identified which selectively inhibit the dormant tuberculosis bacilli with significantly low IC50 values. This study reports the second molecule after TMC‐207, having the ability to inhibit tuberculosis bacilli exclusively in its dormant phase. The synthesis was accomplished by a modified multicomponent Biginelli reaction. A classification model was generated using the binary QSAR approach – recursive partitioning (RP) to identify structural characteristics related to the activity. Physicochemical, structural, topological, connectivity indices, and E‐state key descriptors were used for generation of the decision tree. The decision tree could provide insights into structure–activity relationships that will guide the design of more potent inhibitors.

  DOI：

  10.1111/cbdd.12373

文献信息

• Synthesis, Antileishmanial Activity and Molecular Docking Study of New 3,4-Dihydropyrimidinones/Thiones
  作者：Behnam Mohammadi-Ghalehbin、Saghi Sepehri、Negin Nejatkhah、Sahand Safari、Zahra Hosseinali、Sahar Sabour、Nima Razzaghi-Asl

  DOI：10.1007/s11094-021-02536-4

  日期：2022.1

  Appearance of drug-unresponsive strains of Leishmania genus and toxic side effects of current chemotherapies necessitate the search for novel antileishmanial agents. Within present contribution, new dihydropyrimidine/thione-5-carboxylates/carboxamide derivatives were synthesized and biologically assessed against Leishmania major promastigotes. A few derivatives exhibited promising antileishmanial activities (IC50s 24.7 – 2223.9 μM). Results of biological assessment revealed compound 4 as the most potent antileishmanial agent. Compounds 1, 3, 4, 8 and 9 exhibited significant activity with regard to Glucantime (control drug). For both 5-carboxamide and 5-carboxylate series, it was found that steric hindrance of 4-(3-substituted phenyl) position was determinant in antileishmanial effect proposing a hydrophobic pocket near meta position of 4-phenyl moiety. Molecular docking approach vs. pteridine reductase 1 as a validated leishmanial target revealed that 5-carboxylate derivatives made H-bond with enzyme cofactor, i.e., nicotinamide adenine dinucleotide phosphate (NDP602). Interaction pattern was relatively similar to previously reported drugs such as trimethoprim. Binding efficiency indices (BEIs) were in accordance with antileishmanial IC50 values.

  由于利什曼属出现了对药物无反应的菌株，而目前的化疗又存在毒副作用，因此有必要寻找新型抗利什曼病药物。本研究合成了新的二氢嘧啶/硫酮-5-羧酸盐/甲酰胺衍生物，并对其进行了抗利什曼原虫的生物评估。一些衍生物表现出了良好的抗利什曼病活性（IC50s 24.7 - 2223.9 μM）。生物学评估结果表明，化合物 4 是最有效的抗利什曼病剂。与 Glucantime（对照药物）相比，化合物 1、3、4、8 和 9 具有显著的活性。对于 5-甲酰胺和 5-羧酸盐系列，研究发现 4-（3-取代苯基）位置的立体阻碍是抗利什曼病作用的决定因素，它在 4-苯基分子的元位置附近形成了一个疏水口袋。分子对接方法将蝶啶还原酶 1 作为有效的利什曼病原体靶标，结果表明 5-羧酸盐衍生物与酶的辅助因子（即烟酰胺腺嘌呤二核苷酸磷酸酯（NDP602））产生了 H 键作用。其相互作用模式与之前报道的药物（如三甲氧苄啶）较为相似。结合效率指数（BEIs）与抗利什曼病的 IC50 值一致。
• Discovery and Development of Thiazolo[3,2-a]pyrimidinone Derivatives as General Inhibitors of Bcl-2 Family Proteins
  作者：Bingcheng Zhou、Xun Li、Yan Li、Yaochun Xu、Zhengxi Zhang、Mi Zhou、Xinglong Zhang、Zhen Liu、Jiahai Zhou、Chunyang Cao、Biao Yu、Renxiao Wang

  DOI：10.1002/cmdc.201000484

  日期：2011.5.2

  A class of compounds with a common thiazolo[3,2‐a]pyrimidinone motif has been developed as general inhibitors of Bcl‐2 family proteins. The lead compound was originally identified in a random screening of a small compound library using a fluorescence polarization‐based competitive binding assay. Its binding to the Bcl‐xL protein was further confirmed by 15N‐HSQC NMR experiments. Structural modifications

  一类具有常见的噻唑并[3,2- a ]嘧啶酮基序的化合物已被开发为Bcl-2家族蛋白的一般抑制剂。最初使用基于荧光偏振的竞争结合测定法对小型化合物库进行随机筛选来鉴定先导化合物。15 N-HSQC NMR实验进一步证实了其与Bcl-x L蛋白的结合。分子模型研究的结果指导了对先导化合物的结构修饰。与先导化合物相比，在获得的42种化合物中，许多化合物与Bcl-2家族蛋白的结合亲和力大大提高。最有效的化合物BCL‐LZH‐ 40抑制BH3肽与Bcl‐x L的结合和Bcl-2和Mcl-1的与抑制常数（ķ我）的17，534和200N的中号，分别。
• Targeting Dormant Tuberculosis Bacilli: Results for Molecules with a Novel Pyrimidone Scaffold
  作者：Rohit R. Joshi、Avinash Barchha、Vijay M. Khedkar、Raghuvir R. S. Pissurlenkar、Sampa Sarkar、Dhiman Sarkar、Rohini R. Joshi、Ramesh A. Joshi、Anamik K. Shah、Evans C. Coutinho

  DOI：10.1111/cbdd.12373

  日期：2015.2

  Our inability to completely control TB has been due in part to the presence of dormant mycobacteria. This also renders drug regimens ineffective and is the prime cause of the appearance of drug‐resistant strains. In continuation of our efforts to develop novel antitubercular agents that especially target dormant mycobacteria, a set of 55 new compounds belonging to the pyrimidone class were designed on the basis of CoMFA and CoMSIA studies, and these were synthesized and subsequently tested against both the dormant and virulent BCG strain of M. tuberculosis. Some novel compounds have been identified which selectively inhibit the dormant tuberculosis bacilli with significantly low IC50 values. This study reports the second molecule after TMC‐207, having the ability to inhibit tuberculosis bacilli exclusively in its dormant phase. The synthesis was accomplished by a modified multicomponent Biginelli reaction. A classification model was generated using the binary QSAR approach – recursive partitioning (RP) to identify structural characteristics related to the activity. Physicochemical, structural, topological, connectivity indices, and E‐state key descriptors were used for generation of the decision tree. The decision tree could provide insights into structure–activity relationships that will guide the design of more potent inhibitors.