{4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-(3-nitro-phenyl)-amine

• 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-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-(3-nitro-phenyl)-amine
• 英文别名: 2-Anilino-4-(thiazol-5-yl)pyrimidine deriv. 30；N,4-dimethyl-5-[2-(3-nitroanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine
• 化学式: C₁₅H₁₄N₆O₂S
• 分子量: 342.381
• InChiKey: AXAQVNRYNMCZCK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  137
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-氯-2,4-戊二酮 在 吡啶 、 sodium hydroxide 作用下， 以 甲醇 、 乙二醇甲醚 为溶剂， 反应 40.0h， 生成 {4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl}-(3-nitro-phenyl)-amine
  参考文献：
  名称：

  2-Anilino-4-(thiazol-5-yl)pyrimidine CDK Inhibitors:  Synthesis, SAR Analysis, X-ray Crystallography, and Biological Activity

  摘要：

  Following the identification through virtual screening of 4-(2,4-dimethyl-thiazol-5-yl)pyrimidin-2-ylamines as moderately potent inhibitors of cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analogue program was initiated. The first aims were to optimize potency and to evaluate the cellular mode of action of lead candidate molecules. Here the synthetic chemistry, the structure-guided design approach, and the structure-activity relationships (SARs) that led to the discovery of 2-anilino-4-(thiazol-5-yl)pyrimidine ATP-antagonistic CDK2 inhibitors, many with very low nM K(i)s against CDK2, are reported. Furthermore, X-ray crystal structures of four representative analogues from our chemical series in complex with CDK2 are presented, and these structures are used to rationalize the observed biochemical SARs. Finally results are reported that show, using the most potent CDK2 inhibitor compound from the current series, that the observed antiproliferative and proapoptotic effects are consistent with cellular CDK2 and CDK9 inhibition.

  DOI：

  10.1021/jm0309957

文献信息

• Anti-cancer compounds
  申请人：——

  公开号：US20020019404A1

  公开（公告）日：2002-02-14

  The present invention relates to 2-substituted 4-heteroaryl-pyrimidines, their preparation, pharmaceutical compositions containing them and their use as inhibitors of cyclin-dependent kinases (CDKs) and hence their use in the treatment of proliferative disorders such as cancer, leukaemia, psoriasis and the like.

  本发明涉及2-取代的4-杂环芳基嘧啶、其制备、含有它们的药物组合物以及它们作为细胞周期依赖性激酶（CDKs）抑制剂的用途，因此可用于治疗癌症、白血病、牛皮癣等增生性疾病。
• THIAZOLES AS FUNGICIDES
  申请人：Greul Jorg Nico

  公开号：US20090030024A1

  公开（公告）日：2009-01-29

  Use of compounds of the formula (I), in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and X, Y, Z are as defined in the description as fungicides. Compounds of the formula (Ia), R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 14 , A, X, Y and Z are as defined in the description, process for preparing these compounds and their use for controlling unwanted microorganisms.

  使用式(I)中的化合物，其中R1、R2、R3、R4、R5、R6、R7、R8以及X、Y、Z如描述中定义的作为杀菌剂。式(Ia)中的化合物，R1、R2、R3、R4、R5、R6、R7、R8、R14、A、X、Y和Z如描述中定义，制备这些化合物的方法以及它们用于控制不受欢迎的微生物的用途。
• [EN] 2-SUBSTITUTED 4-HETEROARYL-PYRIMIDINES AND THEIR USE IN THE TREATMETN OF PROLIFERATIVE DISORDERS<br/>[FR] 4-HETEROARYLE-PYRIMIDINES SUBSTITUEES EN 2 ET LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES PROLIFERANTS
  申请人：CYCLACEL LTD

  公开号：WO2001072745A1

  公开（公告）日：2001-10-04

  The present invention relates to 2-substituted 4-heteroaryl-pyrimidines,(Fig.I), wherein: X1 is CH and X2 is S; or one of X?1 and X2¿ is S, and the other of X?1 and X2¿ is N; Z is NH, NHCO, NHSO¿2?, NHCH2, CH2, CH2CH2, or CH=CH; R?1, R2 and R3¿ are independently H, alkyl, aryl, aralkyl, heterocycle, halogeno, NO¿2?, CN, OH, alkoxy, aryloxy, NH2, NH-R', N-(R')(R''), NH-COR', NH-aryl, N-(aryl)2, COOH, COO-R', COO-aryl, CONH2, CONH-R', CON-(R')(R''),CONH-aryl, CON-(aryl)2, SO3H, SO2NH2, CF3, CO-R', or CO-aryl, wherein alkyl, aryl, aralkyl, heterocycle and NH-aryl groups may be further substituted with one or more groups selected from halogeno, NO2, CN, OH, O-methyl, NH2, COOH, CONH2 and CF3; at least one of the groups R?1 and R2¿ being other than H when either X1 or X2 is S; R?4, R5, R6, R7 and R8¿ are independently from each other H, substituted or unsubstituted lower alkyl, halogeno, NO¿2?, CN, OH, substituted or unsubstituted alkoxy, NH2, NH-R', alkyl-aryl, alkyl-heteroaryl, NH(C=NH)NH2, N(R')3?+¿, N(R')(R''), COOH, COO-R', CONH¿2?, CONH-R', CON-(R')(R''), SO3H, SO2NH2, CF3 or (CH2)nO(CH2)m NR'R'', (CH2)nCO2(CH2)mOR''' wherein n is 0,1,2 or 3 and m is 1, 2 or 3; their preparation, pharmaceutical compositions containing them and their use as inhibitors of cyclin-dependant kinases (CDKs) and hence their use in the treatment of proliferative disorders such as cancer, leukaemia, psoriasis and the like.

  本发明涉及2-取代的4-杂环芳基嘧啶（图I），其中：X1为CH，X2为S；或X1和X2中的一个为S，另一个为N；Z为NH，NHCO，NHSO2，NHCH2，CH2，CH2CH2或CH=CH；R1，R2和R3独立地为H，烷基，芳基，芳基烷基，杂环，卤代，NO2，CN，OH，烷氧基，芳氧基，NH2，NH-R'，N-(R')(R'')，NH-COR'，NH-芳基，N-(芳基)2，COOH，COO-R'，COO-芳基，CONH2，CONH-R'，CON-(R')(R'')，CONH-芳基，CON-(芳基)2，SO3H，SO2NH2，CF3，CO-R'或CO-芳基，其中烷基，芳基，芳基烷基，杂环和NH-芳基基团可以进一步取代为卤代，NO2，CN，OH，O-甲基，NH2，COOH，CONH2和CF3中的一种或多种基团；当X1或X2为S时，R1和R2中至少有一个不为H；R4，R5，R6，R7和R8独立地为H，取代或未取代的低级烷基，卤代，NO2，CN，OH，取代或未取代的烷氧基，NH2，NH-R'，烷基-芳基，烷基-杂环芳基，NH(C=NH)NH2，N(R')3+，N(R')(R'')，COOH，COO-R'，CONH2，CONH-R'，CON-(R')(R'')，SO3H，SO2NH2，CF3或(CH2)nO(CH2)mNR'R''，其中n为0，1，2或3，m为1，2或3；它们的制备，包含它们的制药组合物以及它们作为细胞周期依赖性激酶（CDK）的抑制剂的用途，因此在治疗增生性疾病，如癌症，白血病，牛皮癣等方面使用。
• Anti-viral compounds
  申请人：Wang Shudong

  公开号：US20050288307A1

  公开（公告）日：2005-12-29

  The present invention relates to the use of 2-substituted 4-heteroaryl-pyrimidines and related compounds in the treatment of viral disorders.

  本发明涉及使用2-取代的4-杂环基嘧啶和相关化合物治疗病毒性疾病。
• 2-SUBSTITUTED 4-HETEROARYL-PYRIMIDINES AND THEIR USE IN THE TREATMENT OF PROLIFERATIVE DISORDERS
  申请人：Cyclacel Limited

  公开号：EP1274705A1

  公开（公告）日：2003-01-15