3-dimethylamino-1-(2,4-dimethyl-thiazol-5-yl)-propenone | 364334-91-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-dimethylamino-1-(2,4-dimethyl-thiazol-5-yl)-propenone
• 英文别名: 3-(Dimethylamino)-1-(2,4-dimethylthiazol-5-yl)prop-2-en-1-one；3-(dimethylamino)-1-(2,4-dimethyl-1,3-thiazol-5-yl)prop-2-en-1-one
• CAS: 364334-91-8
• 化学式: C₁₀H₁₄N₂OS
• 分子量: 210.3
• InChiKey: NCHMJHFUGUCVFT-UHFFFAOYSA-N

物化性质

• 熔点：
  96-98 °C
• 沸点：
  320.4±42.0 °C(Predicted)
• 密度：
  1.126±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  61.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-dimethylamino-1-(2,4-dimethyl-thiazol-5-yl)-propenone 、 N-(4-guanidino-benzyl)-acetamide nitrate 生成 N-(4-[4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino]-benzyl)-acetamide
  参考文献：
  名称：

  [EN] 2-SUBSTITUTED-4-HETEROARYL-PYRIMIDINES USEFUL FOR THE TREATMENT OF PROLIFERATIVE DISORDERS
  [FR] COMPOSES

  摘要：

  公开号：

  WO2005116025A3
• 作为产物：
  描述：

  2,4-二甲基-5-乙酰基噻唑 、 N,N-二甲基甲酰胺二甲基缩醛 生成 3-dimethylamino-1-(2,4-dimethyl-thiazol-5-yl)-propenone
  参考文献：
  名称：

  N-Phenyl-4-(thiazol-5-yl)pyrimidin-2-amine Aurora Kinase Inhibitors 的发现

  摘要：

  通过对我们的激酶导向化合物集合的基于细胞的筛选，我们发现N-苯基-4-(噻唑-5-基)嘧啶-2-胺的一个子集是针对癌细胞系的有效细胞毒剂，抑制有丝分裂组蛋白 H3磷酸化，并导致异常的有丝分裂表型。随后证实，这些化合物实际上是极光 A 和 B 激酶的有效抑制剂。结果表明，极光激酶抑制的效力和选择性与这些化合物中苯胺对位取代基的存在相关。先导化合物4-甲基-5-(2-(4-morpholinophenylamino)pyrimidin-4-yl)thiazol-2-amine ( 18 ; K i ) 的抗癌作用极光 A 和 B 的值分别为 8.0 和 9.2 nM) 显示来自有丝分裂失败后的细胞死亡和由于细胞抑制极光 A 和 B 激酶而增加的多倍性。初步体内评估表明，化合物18具有口服生物利用度并具有抗癌活性。化合物18 (CYC116) 目前正在癌症患者中进行 I 期临床评估。

  DOI：

  10.1021/jm901913s

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。
• [EN] PYRIDINYLAMINO-PYRIMIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS<br/>[FR] DERIVES DE PYRIDINYLAMINO-PYRIMIDINE UTILES COMME INHIBITEURS DE LA PROTEINE KINASE
  申请人：CYCLACEL LTD

  公开号：WO2005012298A1

  公开（公告）日：2005-02-10

  The present invention relates to compounds of formula I, or pharmaceutically acceptable salts thereof, wherein: (A) 'a' is a single bond and 'b' is a double bond; R1 and R2 are each independently as defined below; R10 is absent; or (B) 'a' is a double bond and 'b' is a single bond; R1 is oxygen; R2 is as defined below; and R10 is H or alkyl; X is S, O, NH, or NR 7; Y is N or CR8; one of Z1, Z2, and Z3 is N or N+Ra and the remainder are each independently CR7; R1, R2, R5 and R6 are each independently R7; R3 and R4 are each independently R8; each R7 is independently H, halogen, NRbRC, ORd or a hydrocarbyl group optionally substituted by one or more R9 groups; each R8 is independently H or (CH2)R9, where n is 0 or 1; each R9 is independently selected from H, halogen, NO2, CN, Re, NHCORf, CF3, CORg, NRhRi, CONRJRk, SO2NR1Rm, SO2Rn, ORp, OCH2CH2ORq, morpholine, piperidine and piperazine; and Ra-q are each independently H or alkyl, wherein said alkyl group is optionally substituted by one or more R9 groups; where the compound is other than [4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-yl]-pyridin­2-yl-amine and 4-[4-fluorophenyl)-1-(1-methyl-4-piperidinyl)-1H-imidazol-5-yl]-N-4­pyridinyl-2-pyrimidinamine. Further aspects of the invention relate to the use of compounds of formula I in the treatment of proliferative disorders, viral disorders, CNS disorders, strokes, alopecia and/or diabetes.

  本发明涉及式I的化合物或其药学上可接受的盐，其中：（A）'a'为单键，'b'为双键；R1和R2各自独立定义如下；R10不存在；或（B）'a'为双键，'b'为单键；R1为氧原子；R2如下定义；R10为H或烷基；X为S、O、NH或NR7；Y为N或CR8；Z1、Z2和Z3中的一个为N或N+Ra，其余各自独立为CR7；R1、R2、R5和R6各自独立为R7；R3和R4各自独立为R8；每个R7各自独立为H、卤素、NRbRC、ORd或一个或多个R9基团可选择地取代的烃基；每个R8各自独立为H或（CH2）R9，其中n为0或1；每个R9各自独立选择自H、卤素、NO2、CN、Re、NHCORf、CF3、CORg、NRhRi、CONRJRk、SO2NR1Rm、SO2Rn、ORp、OCH2CH2ORq、吗啡啉、哌啶和哌嗪；而Ra-q各自独立为H或烷基，其中所述的烷基可以选择地被一个或多个R9基团取代；其中该化合物不是[4-(2,4-二甲基噻唑-5-基)嘧啶-2-基]-吡啶-2-基-胺和4-[4-氟苯基)-1-(1-甲基-4-哌啶基)-1H-咪唑-5-基]-N-4-吡啶基-2-嘧啶胺。本发明的进一步方面涉及使用式I的化合物治疗增殖性疾病、病毒性疾病、中枢神经系统疾病、中风、脱发和/或糖尿病。
• N-(4-(4-methylthiazol-5-yl)pyrimidin-2-yl)-N-phenylamines as antiproliferative compounds
  申请人：——

  公开号：US20040259894A1

  公开（公告）日：2004-12-23

  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, leukemia, psoriasis and the like.

  本发明涉及2-取代的4-杂环芳基嘧啶、它们的制备、含有它们的药物组合物以及它们作为细胞周期蛋白依赖性激酶（CDKs）的抑制剂的用途，因此可用于治疗增殖性疾病，如癌症、白血病、牛皮癣等。
• 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。
• Pyrimidine compounds
  申请人：Wang Shudong

  公开号：US20050192300A1

  公开（公告）日：2005-09-01

  The present invention relates to substituted pyrimidines of formula I, 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 and/or viral disorders.

  本发明涉及式I的取代嘧啶、其制备、含有它们的药物组合物以及它们作为细胞周期蛋白依赖性激酶（CDKs）抑制剂的应用，因此可用于治疗增殖性疾病和/或病毒性疾病。