N-(3-chlorophenyl)-4-phenyl-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxamide | 365242-21-3

• 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: N-(3-chlorophenyl)-4-phenyl-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxamide
• 英文别名: N-(3-Chlorophenyl)-1,2,3,4-tetrahydro-6-methyl-4-phenyl-2-thioxo-5-pyrimidinecarboxamide；N-(3-chlorophenyl)-6-methyl-4-phenyl-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carboxamide
• CAS: 365242-21-3
• 化学式: C₁₈H₁₆ClN₃OS
• 分子量: 357.864
• InChiKey: QGWUAKVKCIPVMV-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

• 作为产物：
  描述：

  3-氯苯胺 以 乙醇 、 甲苯 为溶剂， 生成 N-(3-chlorophenyl)-4-phenyl-6-methyl-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-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

• [EN] 6 - METHYL - 4 - PHENYL - 5 - ( PHENYL OR CYCLOALKYL) CARBAMOYL - 1,2,3, 4 - TETRAHYDROPYRIMIDIN- 2 - ONE DERIVATIVES AS ANTITUBERCULAR AGENTS<br/>[FR] DÉRIVÉS DE 6 - MÉTHYL - 4 - PHÉNYL - 5 - (PHÉNYL OU CYCLOALKYL) CARBAMOYL - 1,2,3, 4 - TÉTRAHYDROPYRIMIDIN- 2 - ONE UTILISÉS EN TANT QU'AGENTS ANTITUBERCULEUX
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2011151701A1

  公开（公告）日：2011-12-08

  The present invention discloses antitubercular compounds selected from tetrahydropyrimidones/ tetrahydrothiopyrimidone derivatives of Formula (1) and its pharmaceutically acceptable salts for the treatment of Mycobacterium in the dormant phase. Formula (1) wherein, R is H, halogen, dihalogen, O-alkyl, di- O-alkyl, R1 is phenyl, chlorophenyl, nitrophenyl, diclorophenyl, cycloalkyl, preferably cyclohexyl, X is O or S.

  本发明公开了选择自公式（1）的四氢嘧啶酮/四氢硫嘧啶酮衍生物以及其药学上可接受的盐的抗结核化合物，用于治疗休眠期结核分枝杆菌。其中，公式（1）中，R为H、卤素、二卤素、O-烷基、二O-烷基，R1为苯基、氯苯基、硝基苯基、二氯苯基、环烷基，优选环己基，X为O或S。
• 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.