4-(2,4-二甲基-1,3-噻唑)-2-氨基嘧啶 | 364334-94-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-(2,4-二甲基-1,3-噻唑)-2-氨基嘧啶
• 英文名称: 4-(2,4-dimethylthiazol-5-yl)pyrimidin-2-ylamine
• 英文别名: 4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamine；4-(2,4-Dimethyl-1,3-thiazol-5-YL)pyrimidin-2-amine
• CAS: 364334-94-1
• 化学式: C₉H₁₀N₄S
• 分子量: 206.271
• InChiKey: CTFDMGIBHFQWKB-UHFFFAOYSA-N

物化性质

• 沸点：
  426.1±37.0 °C(Predicted)
• 密度：
  1.299±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  92.9
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2934100090

反应信息

• 作为反应物：
  描述：

  4-(2,4-二甲基-1,3-噻唑)-2-氨基嘧啶 以 吡啶 、 乙酸乙酯 为溶剂， 生成 N-{4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl}-3-nitro-benzenesulfonamide
  参考文献：
  名称：

  Anti-cancer compounds

  摘要：

  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。

  公开号：

  US20020019404A1
• 作为产物：
  描述：

  2,4-二甲基-5-乙酰基噻唑 在 sodium hydroxide 作用下， 以 乙二醇甲醚 为溶剂， 反应 43.0h， 生成 4-(2,4-二甲基-1,3-噻唑)-2-氨基嘧啶
  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

• [EN] SUBSTITUTED 2, 4-DIAMINO-QUINOLINE DERIVATIVES FOR USE IN THE TREATMENT OF PROLIFERATIVE DISEASES<br/>[FR] DÉRIVÉS SUBSTITUÉS DE 2, 4-DIAMINO-QUINOLÉINE POUR LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES PROLIFÉRATIVES
  申请人：GENOSCIENCE PHARMA

  公开号：WO2017191599A1

  公开（公告）日：2017-11-09

  This application discloses compounds according to generic Formula (I): wherein all variables are defined as described herein which exhibit strong inhibition effects on various cancer cell lines. The compounds disclosed herein are useful for the treatment of proliferative diseases, including neoplastic diseases such as cancer and non- neoplastic disorders such as rheumatoid arthritis. Also disclosed are pharmaceutical compositions containing compounds of Formula (I) and at least one carrier, diluent or excipient and optionally one or more additional therapeutically active agents, including anticancer agents. This application also discloses methods for treating a proliferative disease, including neoplastic diseases such as cancer and non- neoplastic disorders such as rheumatoid arthritis.

  本申请披露了根据通用式（I）定义的化合物，其中所有变量如本文所述，这些化合物对各种癌细胞系表现出强烈的抑制作用。本文披露的化合物对于治疗增生性疾病非常有用，包括肿瘤性疾病如癌症和非肿瘤性疾病如类风湿性关节炎。还披露了含有通用式（I）化合物和至少一种载体、稀释剂或赋形剂以及可选的一种或多种其他治疗活性剂的药物组合物。本申请还披露了治疗增生性疾病的方法，包括肿瘤性疾病如癌症和非肿瘤性疾病如类风湿性关节炎的方法。
• [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。
• Advanced drug development and manufacturing
  申请人：Los Alamos National Security, LLC

  公开号：EP2511844A2

  公开（公告）日：2012-10-17

  There is described an apparatus for measuring protein characteristics comprising an X-ray fluorescence (XRF) spectrometer comprising a source of polychromatic X-rays, an X-ray detector, a protein, a molecule that has been exposed to and at least weakly binds to the protein, a plurality of X-ray fluorescence signal data obtained by irradiating chemical elements in the protein and molecule with the polychromatic X-rays and a security system for maintaining records for the data from the plurality of X-ray fluorescence signal measurements. There is also described an x-ray microscope for measuring a sample.

  描述了一种测量蛋白质特性的仪器，该仪器包括一个 X 射线荧光 (XRF) 光谱仪，其中包括一个多色 X 射线源、一个 X 射线探测器、一个蛋白质、一个已暴露于该蛋白质并至少与该蛋白质弱结合的分子、通过用多色 X 射线照射蛋白质和分子中的化学元素而获得的多个 X 射线荧光信号数据，以及一个用于维护多个 X 射线荧光信号测量数据记录的安全系统。此外，还介绍了一种用于测量样品的 X 射线显微镜。
• Substituted 2, 4-diamino-quinoline derivatives for use in the treatment of proliferative diseases
  申请人：GENOSCIENCE PHARMA

  公开号：US10577362B2

  公开（公告）日：2020-03-03

  This application discloses compounds according to generic Formula I: wherein all variables are defined as described herein which exhibit strong inhibition effects on various cancer cell lines. The compounds disclosed herein are useful for the treatment of proliferative diseases, including neoplastic diseases such as cancer and non-neoplastic disorders such as rheumatoid arthritis. Also disclosed are pharmaceutical compositions containing compounds of Formula I and at least one carrier, diluent or excipient and optionally one or more additional therapeutically active agents, including anticancer agents. This application also discloses methods for treating a proliferative disease, including neoplastic diseases such as cancer and non-neoplastic disorders such as rheumatoid arthritis.

  本申请公开了符合通式 I 的化合物：其中所有变量的定义如本文所述，这些化合物对各种癌细胞系具有很强的抑制作用。本文公开的化合物可用于治疗增殖性疾病，包括肿瘤性疾病（如癌症）和非肿瘤性疾病（如类风湿性关节炎）。本申请还公开了含有式 I 化合物和至少一种载体、稀释剂或赋形剂的药物组合物，以及一种或多种额外的治疗活性剂，包括抗癌剂。本申请还公开了治疗增殖性疾病的方法，包括肿瘤性疾病如癌症和非肿瘤性疾病如类风湿性关节炎。