5-acetyl-3,4-dimethylthiazol-2(3H)-one | 32497-15-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-acetyl-3,4-dimethylthiazol-2(3H)-one
• 英文别名: 5-acetyl-3,4-dimethyl-3H-thiazol-2-one；5-acetyl-3,4-dimethyl-3H-thiazol-2-one；5-acetyl-3,4-dimethyl-1,3-thiazol-2-one
• CAS: 32497-15-7
• 化学式: C₇H₉NO₂S
• 分子量: 171.22
• InChiKey: KLBJEBADZSVSPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  62.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-acetyl-3,4-dimethylthiazol-2(3H)-one 在 sodium hydroxide 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 5-(2-(4-chloro-2-methoxyphenylamino)pyrimidin-4-yl)-3,4-dimethylthiazol-2(3H)-one
  参考文献：
  名称：

  发现作为有效Mnk2抑制剂的5-（2-（苯氨基）嘧啶-4-基）噻唑-2（3H）-one衍生物：合成，SAR分析和生物学评估

  摘要：

  人类促分裂原激活蛋白激酶（MAPK）相互作用激酶（Mnks）对eIF4E的磷酸化对于人类肿瘤的发生和发展至关重要。靶向Mnks可能提供一种新颖的抗癌治疗策略。然而，迄今为止缺乏选择性的Mnk抑制剂已经阻碍了药理学靶标的验证和临床药物的开发。在此，我们首次报告了一系列5-（2-（苯基氨基）嘧啶-4-基）噻唑-2（3 H一种衍生物作为Mnk抑制剂。几种衍生物表现出非常强的Mnk2抑制活性。针对一组癌细胞系测试了最具活性和选择性的化合物，结果证实了这些Mnk抑制剂的细胞类型特异性作用。详细的细胞机制研究表明，Mnk抑制剂能够降低抗凋亡蛋白Mcl-1的表达水平，并能促进MV4-11急性髓性白血病细胞的凋亡。

  DOI：

  10.1002/cmdc.201300552
• 作为产物：
  描述：

  3-氯-2,4-戊二酮 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 20.0h， 生成 5-acetyl-3,4-dimethylthiazol-2(3H)-one
  参考文献：
  名称：

  发现作为有效Mnk2抑制剂的5-（2-（苯氨基）嘧啶-4-基）噻唑-2（3H）-one衍生物：合成，SAR分析和生物学评估

  摘要：

  人类促分裂原激活蛋白激酶（MAPK）相互作用激酶（Mnks）对eIF4E的磷酸化对于人类肿瘤的发生和发展至关重要。靶向Mnks可能提供一种新颖的抗癌治疗策略。然而，迄今为止缺乏选择性的Mnk抑制剂已经阻碍了药理学靶标的验证和临床药物的开发。在此，我们首次报告了一系列5-（2-（苯基氨基）嘧啶-4-基）噻唑-2（3 H一种衍生物作为Mnk抑制剂。几种衍生物表现出非常强的Mnk2抑制活性。针对一组癌细胞系测试了最具活性和选择性的化合物，结果证实了这些Mnk抑制剂的细胞类型特异性作用。详细的细胞机制研究表明，Mnk抑制剂能够降低抗凋亡蛋白Mcl-1的表达水平，并能促进MV4-11急性髓性白血病细胞的凋亡。

  DOI：

  10.1002/cmdc.201300552

文献信息

• [EN] PYRIMIDINE COMPOUNDS<br/>[FR] COMPOSES DE PYRIMIDINE
  申请人：CYCLACEL LTD

  公开号：WO2004043953A1

  公开（公告）日：2004-05-27

  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)的取代嘧啶化合物，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依赖性激酶（CDKs）抑制剂的用途，因此可用于治疗增殖性疾病和/或病毒性疾病。
• [EN] PYRIMIDIN-4-YL-3, 4-THIONE COMPOUNDS AND THEIR USE IN THERAPY<br/>[FR] COMPOSES DE PYRIMIDIN-4-YL-3, 4-THIONE ET LEUR UTILISATION A DES FINS THERAPEUTIQUES
  申请人：CYCLACEL LTD

  公开号：WO2005042525A1

  公开（公告）日：2005-05-12

  The present invention relates to compounds of formula: (I), or pharmaceutically acceptable salts thereof, wherein R1 and R5 are each independently H, C(ORj’) or a hydrocarbyl group optionally substituted by one or more R6 groups; R2, R3, and R4 are each independently H, alkyl or alkenyl, each of which may be optionally substituted with one or more R7 groups; R6 and R7 are each independently halogen, NO2, CN, (CH2)mORa, O(CH2)nORb, (CH2)pNRcRd, CF3, COORe, CONRfRg, CORh, SO3H, SO2Ri, SO2NRjRk, (CH2)qNRa’CORg’, Rf’, (CH2)rNRb’SO2Rh’, SO2NRd’Ri’, SO2NRe'(CH2)s,ORc', heterocycloalkyl or heteroaryl, wherein said heterocycloalkyl and heteroaryl may be optionally substituted by one or more substituents selected from aralkyl, sulfonyl, Rm and CORn; Rg', Rh', Ri' and Rj' are each independently selected from alkyl, aryl, aralkyl and heteroaryl, each of which may be optionally substituted with one or more substituents selected from halogen, OH, NO2, NH2 CF3 and COOH; m, p, q and r are each independently 0, 1, 2 or 3; n and s are each independently 1, 2, or 3; and Ra-n and Ra'-f' are each independently H or alkyl. Further aspects of the invention relate to pharmaceutical compositions comprising such compounds, and their use in the preparation of a medicament for treating one or more of the following: a proliferative disorder, a viral disorder, a CNS disorder, a stroke, alopecia and diabetes.

  本发明涉及以下结构的化合物：(I)，或其药学上可接受的盐，其中R1和R5分别独立地为H、C(ORj’)或一个或多个R6基团取代的烃基团；R2、R3和R4分别独立地为H、烷基或烯基，每个基团可能选择性地用一个或多个R7基团取代；R6和R7分别独立地为卤素、NO2、CN、(CH2)mORa、O(CH2)nORb、(CH2)pNRcRd、CF3、COORe、CONRfRg、CORh、SO3H、SO2Ri、SO2NRjRk、(CH2)qNRa’CORg’、Rf’、(CH2)rNRb’SO2Rh’、SO2NRd’Ri’、SO2NRe'(CH2)s、ORc'、杂环烷基或杂芳基，其中所述的杂环烷基和杂芳基可以选择性地用一个或多个从芳基烷基、磺酰基、Rm和CORn中选择的取代基团取代；Rg'、Rh'、Ri'和Rj'分别独立地选择自烷基、芳基、芳基烷基和杂芳基，每个基团可能选择性地用一个或多个从卤素、OH、NO2、NH2、CF3和COOH中选择的取代基团取代；m、p、q和r分别独立地为0、1、2或3；n和s分别独立地为1、2或3；以及Ra-n和Ra'-f'分别独立地为H或烷基。本发明的进一步方面涉及包含这种化合物的药物组合物，以及它们在制备治疗以下一种或多种疾病的药物中的用途：增生性疾病、病毒性疾病、中枢神经系统疾病、中风、脱发和糖尿病。
• 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。
• Pyrimidin-4-YL-3, 4-thione compounds and their use in therapy
  申请人：Wang Shudong

  公开号：US20070021452A1

  公开（公告）日：2007-01-25

  The present invention relates to compounds of formula I, or pharmaceutically acceptable salts thereof, wherein R 1 and R 5 are each independently H, C(OR j′ ) or a hydrocarbyl group optionally substituted by one or more R 6 groups; R 2 , R 3 , and R 4 are each independently H, alkyl or alkenyl, each of which may be optionally substituted with one or more R 7 groups; R 6 and R 7 are each independently halogen, NO 2 , CN, (CH 2 ) m OR a , O(CH 2 ) n OR b , (CH 2 ) p NR c R d , CF 3 , COOR e , CONR f R g , COR h , SO 3 H, SO 2 R i , SO 2 NR j R k , (CH 2 ) q NR a′ COR g′ , R f′ , (CH 2 ) r NR b′ SO 2 R h′ , SO 2 NR d′ R i′ , SO 2 NR e′ (CH 2 ) s OR c′ , heterocycloalkyl or heteroaryl, wherein said heterocycloalkyl and heteroaryl may be optionally substituted by one or more substituents selected from aralkyl, sulfonyl, R m and COR n ; R g′ , R h′ , R i′ and R j′ are each independently selected from alkyl, aryl, aralkyl and heteroaryl, each of which may be optionally substituted with one or more substituents selected from halogen, OH, NO 2 , NH 2 CF 3 and COOH; m, p, q and r are each independently 0, 1, 2 or 3; n and s are each independently 1, 2, or 3; and R a-n and R a′-f′ are each independently H or alkyl. Further aspects of the invention relate to pharmaceutical compositions comprising such compounds, and their use in the preparation of a medicament for treating one or more of the following: a proliferative disorder, a viral disorder, a CNS disorder, a stroke, alopecia and diabetes.

  本发明涉及公式I的化合物或其药学上可接受的盐，其中R1和R5各自独立地为H，C（ORj'）或一种或多种R6基团选择性取代的烃基基团；R2，R3和R4各自独立地为H，烷基或烯基，每个基团都可以选择性地用一种或多种R7基团取代；R6和R7各自独立地为卤素，NO2，CN，（CH2）mORa，O（CH2）nORb，（CH2）pNRcRd，CF3，COORe，CONRfRg，CORh，SO3H，SO2Ri，SO2NRjRk，（CH2）qNRa′CORg′，Rf′，（CH2）rNRb′SO2Rh′，SO2NRd′Ri′，SO2NRe′（CH2）sORc′，杂环烷基或杂环芳基，其中所述杂环烷基和杂环芳基可以选择性地用一种或多种取代基选自芳基烷基，磺酰基，Rm和CORn取代；Rg'，Rh'，Ri'和Rj'各自独立地选择自烷基，芳基，芳基烷基和杂环芳基，每个基团都可以选择性地用一种或多种取代基选自卤素，OH，NO2，NH2，CF3和COOH；m，p，q和r各自独立地为0，1，2或3；n和s各自独立地为1，2或3；以及Ra-n和Ra′-f′各自独立地为H或烷基。本发明的另一方面涉及包含这种化合物的制药组合物，以及它们在制备用于治疗增殖性疾病、病毒性疾病、中枢神经系统疾病、中风、脱发和糖尿病的药物的过程中的应用。
• Pyrimidin-4-yl-3, 4-thione compounds and their use in therapy
  申请人：Cyclacel Limited

  公开号：US07902361B2

  公开（公告）日：2011-03-08

  The present invention relates to compounds of formula I, or pharmaceutically acceptable salts thereof, wherein R1 and R5 are each independently H, C(ORj′) or a hydrocarbyl group optionally substituted by one or more R6 groups; R2, R3, and R4 are each independently H, alkyl or alkenyl, each of which may be optionally substituted with one or more R7 groups; R6 and R7 are each independently halogen, NO2, CN, (CH2)mORa, O(CH2)nORb, (CH2)pNRcRd, CF3, COORe, CONRfRg, CORh, SO3H, SO2Ri, SO2NRjRk, (CH2)qNRa′CORg′, Rf′, (CH2)rNRb′SO2Rh′, SO2NRd′Ri′, SO2NRe′(CH2)sORc′, heterocycloalkyl or heteroaryl, wherein said heterocycloalkyl and heteroaryl may be optionally substituted by one or more substituents selected from aralkyl, sulfonyl, Rm and CORn; Rg′, Rh′, Ri′ and Rj′ are each independently selected from alkyl, aryl, aralkyl and heteroaryl, each of which may be optionally substituted with one or more substituents selected from halogen, OH, NO2, NH2 CF3 and COOH; m, p, q and r are each independently 0, 1, 2 or 3; n and s are each independently 1, 2, or 3; and Ra-n and Ra′-f′ are each independently H or alkyl. Further aspects of the invention relate to pharmaceutical compositions comprising such compounds, and their use in the preparation of a medicament for treating one or more of the following: a proliferative disorder, a viral disorder, a CNS disorder, a stroke, alopecia and diabetes.

  本发明涉及式I的化合物或其药学上可接受的盐，其中R1和R5各自独立地为H、C（ORj'）或一种或多种R6基团选择性取代的烃基基团；R2、R3和R4各自独立地为H、烷基或烯基，每个基团均可以选择性地用一种或多种R7基团取代；R6和R7各自独立地为卤素、NO2、CN、（CH2）mORa、O（CH2）nORb、（CH2）pNRcRd、CF3、COORe、CONRfRg、CORh、SO3H、SO2Ri、SO2NRjRk、（CH2）qNRa′CORg′、Rf′、（CH2）rNRb′SO2Rh′、SO2NRd′Ri′、SO2NRe′（CH2）sORc′、杂环烷基或杂环芳基，其中所述的杂环烷基和杂环芳基可以选择性地用一种或多种取代基选自芳基烷基、磺酰基、Rm和CORn取代；Rg'、Rh'、Ri'和Rj'各自独立地选自烷基、芳基、芳基烷基和杂环芳基，每个基团均可以选择性地用一种或多种取代基选自卤素、OH、NO2、NH2、CF3和COOH取代；m、p、q和r各自独立地为0、1、2或3；n和s各自独立地为1、2或3；以及Ra-n和Ra′-f′各自独立地为H或烷基。本发明的进一步方面涉及包含这种化合物的药物组合物，以及它们在制备用于治疗以下一种或多种疾病的药物的过程中的使用：增生性疾病、病毒性疾病、中枢神经系统疾病、中风、脱发和糖尿病。