4-氯-6-甲基-2-(2-吡啶)嘧啶 | 77168-31-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4-氯-6-甲基-2-(2-吡啶)嘧啶
• 中文别名: 2-吡啶-2-基-4-氯-6-甲基嘧啶
• 英文名称: 4-chloro-6-methyl-2-(pyridin-2-yl)pyrimidine
• 英文别名: 4-chloro-6-methyl-2-(2-pyridinyl)pyrimidine；4-chloro-6-methyl-2-pyridin-2-ylpyrimidine
• CAS: 77168-31-1
• 化学式: C₁₀H₈ClN₃
• mdl: MFCD00662786
• 分子量: 205.647
• InChiKey: QXTIZJZQBKJJCB-UHFFFAOYSA-N

物化性质

• 熔点：
  75-76°C
• 沸点：
  250.3±22.0 °C(Predicted)
• 密度：
  1.264±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 安全说明：
  S26,S36/37/39
• 危险类别码：
  R20/21/22,R36/37/38
• 海关编码：
  2933990090
• 储存条件：
  室温、密封、干燥

反应信息

• 作为反应物：
  描述：

  4-氯-6-甲基-2-(2-吡啶)嘧啶 在 硫脲 作用下， 以 乙醇 为溶剂， 反应 20.0h， 以74%的产率得到6-methyl-2-(pyridin-2'-yl)pyrimidine-4(3H)-thione
  参考文献：
  名称：

  Brown, Desmond J.; Cowden, William B.; Grigg, Geoffrey W., Australian Journal of Chemistry, 1980, vol. 33, # 10, p. 2291 - 2298

  摘要：

  DOI：
• 作为产物：
  描述：

  2-脒基吡啶盐酸盐 在 sodium methylate 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 4-氯-6-甲基-2-(2-吡啶)嘧啶
  参考文献：
  名称：

  Pyridinylpyrimidines selectively inhibit human methionine aminopeptidase-1

  摘要：

  Cellular protein synthesis is initiated with methionine in eukaryotes with few exceptions. Methionine aminopeptidases (MetAPs) which catalyze the process of N-terminal methionine excision are essential for all organisms. In mammals, type 2 MetAP (MetAP2) is known to be important for angiogenesis, while type 1 MetAP (MetAP1) has been shown to play a pivotal role in cell proliferation. Our previous high-throughput screening of a commercial compound library uncovered a novel class of inhibitors for both human MetAP1 (HsMetAP1) and human MetAP2 (HsMetAP2). This class of inhibitors contains a pyridinylpyrimidine core. To understand the structure-activity relationship (SAR) and to search for analogues of 2 with greater potency and higher HsMetAP1-selectivity, a total of 58 analogues were acquired through either commercial source or by in-house synthesis and their inhibitory activities against HsMetAP1 and HsMetAP2 were determined. Through this systematic medicinal chemistry analysis, we have identified (1) 5-chloro-6-methyl-2-pyridin-2-ylpyrimidine as the minimum element for the inhibition of HsMetAP1; (2) 5'-chloro as the favored substituent on the pyridine ring for the enhanced potency against HsMetAP1; and (3) long C4 side chains as the essentials for higher HsMetAP1-selectivity. At the end of our SAR campaign, 25b, 25c, 26d and 30a-30c are among the most selective and potent inhibitors of purified HsMetAP1 reported to date. In addition, we also performed crystallographic analysis of one representative inhibitor (26d) in complex with N-terminally truncated HsMetAP1. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.02.023

文献信息

• Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators or caspases and inducers of apoptosis and the use thereof
  申请人：Cytovia, Inc.

  公开号：US20030069239A1

  公开（公告）日：2003-04-10

  The present invention is directed to substituted 2-aryl-4-arylaminopyrimidine and analogs thereof, represented by the general Formula I: 1 wherein A, Ar 1 , Ar 2 , R 1 and R 3 are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. The compounds of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明涉及被一般式I所代表的取代的2-芳基-4-芳基氨基嘧啶及其类似物： 其中A，Ar1，Ar2，R1和R3在此处被定义。本发明还涉及发现具有式I的化合物是caspase的激活剂和凋亡诱导剂。本发明的化合物可用于诱导在出现未受控制的异常细胞生长和扩散的各种临床病况中的细胞死亡。
• POTASSIUM CHANNEL MODULATORS
  申请人：Cadent Therapeutics, Inc.

  公开号：US20170355708A1

  公开（公告）日：2017-12-14

  Provided are novel compounds of Formula (I): and pharmaceutically acceptable salts thereof, which are useful for treating a variety of diseases, disorders or conditions, associated with potassium channels. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I), pharmaceutically acceptable salts thereof, and methods for their use in treating one or more diseases, disorders or conditions, associated with potassium channels.

  提供的是公式(I)的新颖化合物： 以及它们的药用可接受盐，这些化合物用于治疗与钾通道相关的一系列疾病、障碍或状况。还提供了包含公式(I)的新颖化合物的药物组合物，它们的药用可接受盐，以及使用它们来治疗与钾通道相关的一种或多种疾病、障碍或状况的方法。
• Unfused heterobicycles as amplifiers of phleomycin. V. A range of pyridinylpyrimidines with strongly basic side chains
  作者：DJ Brown、WB Cowden

  DOI：10.1071/ch9821203

  日期：——

  The condensation of 3-aminocrotonamide with ethyl pyridine-2-carboxylate or a related ester gave 6-methylpyrimidin-4(3H)-ones, each bearing at its 2-position a pyridin-2'-yl, pyridin-3'-yl, pyridin- 4'-yl, furan-2'-yl, furan-3'-yl, thien-2'-yl or pyrazin-2'-yl substituent. Of these, the pyridinyl derivatives (1a), (2a) and (3a) were converted into their 4-chloro analogues and thence by nucleophilic displacement into the corresponding β-dimethylaminoethylthio, β-dimethylaminoethylamino, β-dimethylaminoethoxy and γ-dimethylaminopropylamino derivatives. The activities of these compounds as amplifiers of phleomycin against Escherichia coli are reported.

  将 3-aminocrotonamide 与吡啶-2-羧酸乙酯或相关酯类缩合后得到 6-甲基嘧啶-4(3H)-酮，每个酮的 2-位上都含有吡啶-2'-基、吡啶-3'-基、吡啶-4'-基、呋喃-2'-基 2'-基、吡啶-3'-基、吡啶-4'-基、呋喃-2'-基、呋喃-3'-基、噻吩-2'-基或吡嗪-2'-基。 或吡嗪-2'-基取代基。其中，吡啶基衍生物 (1a)、(2a) 和 (3a) (3a) 转化为它们的 4-氯类似物，然后通过亲核 置换成相应的 β-二甲氨基乙硫基、β-二甲氨基乙氨基、 β-二甲氨基乙氧基和 γ-二甲氨基丙基氨基衍生物。这些 报告了这些化合物作为夫来霉素的放大剂对大肠杆菌的活性。
• Synthesis and evaluation of 2-pyridyl pyrimidines with in vitro antiplasmodial and antileishmanial activity
  作者：Chitalu C. Musonda、Gavin A. Whitlock、Michael J. Witty、Reto Brun、Marcel Kaiser

  DOI：10.1016/j.bmcl.2008.11.098

  日期：2009.1

  A series of 2-pyridyl pyrimidines, reported inhibitors of Plasmodium falciparum methionine aminopeptidase 1b were synthesized and evaluated for their antiplasmodial activities. An analysis of physicochemical properties demonstrated a link between lipophilicity and antiparasitic activity. Cross screening of the library against cultured Leishmania donovani parasites revealed this class of compounds as

  合成了一系列2-吡啶基嘧啶，已报道恶性疟原虫蛋氨酸氨基肽酶1b的抑制剂，并评估了它们的抗血浆活性。理化性质的分析表明亲脂性和抗寄生虫活性之间的联系。针对培养的利什曼原虫donovani寄生虫的文库的交叉筛选揭示了这类化合物是体外寄生虫发展的有效抑制剂。
• Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators of caspases and inducers of apoptosis and the use thereof
  申请人：Cytovia, Inc.

  公开号：US20040097503A1

  公开（公告）日：2004-05-20

  The present invention is directed to substituted 2-aryl-4-arylaminopyrimidine and analogs thereof, represented by the general Formula I: 1 wherein A, Ar 1 , Ar 2 , R 1 and R 3 are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. The compounds of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明涉及取代的2-芳基-4-芳氨基嘧啶及其类似物，由通式I表示：其中A、Ar1、Ar2、R1和R3如本文所定义。本发明还涉及发现具有I式化合物的活化剂和凋亡诱导剂。本发明的化合物可用于在各种临床情况下诱导细胞死亡，其中出现了不受控制的异常细胞的生长和扩散。