1-((2-ethylamino)4-methylthiazol-5-yl)-ethanone | 507488-34-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-((2-ethylamino)4-methylthiazol-5-yl)-ethanone
• 英文别名: 1-[2-(Ethylamino)-4-methyl-1,3-thiazol-5-yl]ethan-1-one；1-[2-(ethylamino)-4-methyl-1,3-thiazol-5-yl]ethanone
• CAS: 507488-34-8
• 化学式: C₈H₁₂N₂OS
• mdl: MFCD20542142
• 分子量: 184.262
• InChiKey: WDQSJXGTBWEXCK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  70.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-((2-ethylamino)4-methylthiazol-5-yl)-ethanone 在 sodium hydroxide 作用下， 以 乙二醇甲醚 为溶剂， 反应 44.0h， 生成 3-{4-(2-Ethylamino-4-methyl-thiazol-5-yl)-pyrimidin-2-ylamino}-phenol
  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
• 作为产物：
  描述：

  乙基硫脲 、 3-氯-2,4-戊二酮 以 丙酮 为溶剂， 反应 1.5h， 生成 1-((2-ethylamino)4-methylthiazol-5-yl)-ethanone
  参考文献：
  名称：

  Thiazole-based aminopyrimidines and N-phenylpyrazolines as potent antimicrobial agents: synthesis and biological evaluation

  摘要：

  一系列基于噻唑的8个N-苯基吡唑啉和两个氨基嘧啶，其前体为几种查尔酮衍生物，已经合成并评估其抗微生物活性。

  DOI：

  10.1039/c4md00124a

文献信息

• Discovery of <i>N</i>-Phenyl-4-(thiazol-5-yl)pyrimidin-2-amine Aurora Kinase Inhibitors
  作者：Shudong Wang、Carol A. Midgley、Frederic Scaërou、Joanna B. Grabarek、Gary Griffiths、Wayne Jackson、George Kontopidis、Steven J. McClue、Campbell McInnes、Christopher Meades、Mokdad Mezna、Andy Plater、Iain Stuart、Mark P. Thomas、Gavin Wood、Rosemary G. Clarke、David G. Blake、Daniella I. Zheleva、David P. Lane、Robert C. Jackson、David M. Glover、Peter M. Fischer

  DOI：10.1021/jm901913s

  日期：2010.6.10

  compounds were in fact potent inhibitors of aurora A and B kinases. It was shown that potency and selectivity of aurora kinase inhibition correlated with the presence of a substituent at the aniline para-position in these compounds. The anticancer effects of lead compound 4-methyl-5-(2-(4-morpholinophenylamino)pyrimidin-4-yl)thiazol-2-amine (18; Ki values of 8.0 and 9.2 nM for aurora A and B, respectively)

  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。
• In vitro antioxidant activity of thiazolidinone derivatives of 1,3-thiazole and 1,3,4-thiadiazole
  作者：Mirjana Djukic、Mara Fesatidou、Iakovos Xenikakis、Athina Geronikaki、Violina T. Angelova、Vladimir Savic、Marta Pasic、Branislav Krilovic、Dusan Djukic、Borko Gobeljic、Marina Pavlica、Ana Djuric、Ivan Stanojevic、Danilo Vojvodic、Luciano Saso

  DOI：10.1016/j.cbi.2018.03.013

  日期：2018.4

  Vitamin C 94.35%, Vitamin E 2.99% and α-LA 1.57%; compounds: 4 33.98%; 2 18.73%; 1 15.62%; 5 6.59%; 3 4.99%; 6-9 demonstrated almost no AOA. The results of TBARS testing (% of LPO inhibition): Vitamin C 62.32%; Vitamin E 36.29%; α-LA 51.36%; compounds: 1 62.11%; 5 66.71%; 9 60.93%; 4, 6 and 7 demonstrated ∼50%; 3 and 8 displayed ∼38%; 2 23.51%. By FRAP method, Vitamins E and C showed equal AOA, ∼100%

  临床前药物开发研究的初始步骤涉及用于特定治疗用途的新化合物的合成，需要通过体外然后体内测试来确认。九种噻唑烷酮衍生物（数字标记为1-9）分类如下：基于1,3-噻唑的化合物（1和2）；1,3,4-噻二唑类化合物（3和4）; 取代的5-亚苄基-2-金刚烷噻唑[3,2-b] [1,2,4]三唑-6（5H）酮（5-8）；通过使用三种体外测定法测试DPPH（1,1-二苯基-2-吡啶并肼基清除能力测试）和基于乙基氨基噻唑的查尔酮（9）的抗氧化活性（AOA）。FRAP（铁还原抗氧化剂能力测试）；和TBARS（硫代巴比妥酸反应性物质测试）。化合物1-4和9尤其是新合成的化合物。还，测试了传统的抗氧化剂维生素E，C和α-硫辛酸（α-LA）。DPPH测试结果：维生素C 94.35％，维生素E 2.99％和α-LA1.57％；化合物：4 33.98％; 2 18.73％; 1 15.62％; 5 6.59％; 3
• [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。
• Discovery of novel JAK2 and EGFR inhibitors from a series of thiazole-based chalcone derivatives
  作者：Kamonpan Sanachai、Thitinan Aiebchun、Panupong Mahalapbutr、Supaphorn Seetaha、Lueacha Tabtimmai、Phornphimon Maitarad、Iakovos Xenikakis、Athina Geronikaki、Kiattawee Choowongkomon、Thanyada Rungrotmongkol

  DOI：10.1039/d0md00436g

  日期：——

  The Janus kinase (JAK) and epidermal growth factor receptor (EGFR) have been considered as potential targets for cancer therapy due to their role in regulating proliferation and survival of cancer cells.

  Janus激酶（JAK）和表皮生长因子受体（EGFR）由于它们在调节癌细胞增殖和生存方面的作用，被认为是癌症治疗的潜在靶点。
• [EN] N-(4-(4-METHYLTHIAZOL-5-YL) PYRIMIDIN-2-YL) -N-PHENYLAMINES AS ANTIPROLIFERATIVE COMPOUNDS<br/>[FR] N-(4-(4-METHYLTHIAZOL-5-YL) PYRIMIDINE-2-YL) -N-PHENYLAMINES COMME COMPOSES A ACTION ANTIPROLIFERANTE
  申请人：CYCLACEL LTD

  公开号：WO2003029248A1

  公开（公告）日：2003-04-10

  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，它们的制备，包含它们的药物组合物以及它们作为细胞周期依赖性激酶（CDKs）的抑制剂的用途，因此可用于治疗增生性疾病，如癌症、白血病、牛皮癣等。