2-chloro-N-(p-tolyl)pyrimidin-4-amine | 260045-64-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-chloro-N-(p-tolyl)pyrimidin-4-amine
• 英文别名: 2-chloro-N-(4-methylphenyl)pyrimidin-4-amine
• CAS: 260045-64-5
• 化学式: C₁₁H₁₀ClN₃
• mdl: MFCD06253507
• 分子量: 219.673
• InChiKey: WJKYNRHPUJHXRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(p-tolyl)pyrimidin-4-amine 在 potassium carbonate 作用下， 以 甲醇 、 二甲基亚砜 、 正丁醇 为溶剂， 生成 2,4-Bis anilino pyrimidine deriv. 10
  参考文献：
  名称：

  细胞周期蛋白依赖性激酶4抑制剂可治疗癌症。第2部分：取代的2,4-双苯胺嘧啶的鉴定和优化。

  摘要：

  通过化学修饰和X射线晶体学，我们确定了2,4-双苯胺嘧啶是CDK4的有效抑制剂。在此，我们描述了该系列的优化。

  DOI：

  10.1016/s0960-894x(03)00203-8
• 作为产物：
  描述：

  2,4-二氯嘧啶 、 乙烷,三氯氟- 在 N,N-二异丙基乙胺 作用下， 以 正丁醇 为溶剂， 生成 2-chloro-N-(p-tolyl)pyrimidin-4-amine
  参考文献：
  名称：

  细胞周期蛋白依赖性激酶4抑制剂可治疗癌症。第2部分：取代的2,4-双苯胺嘧啶的鉴定和优化。

  摘要：

  通过化学修饰和X射线晶体学，我们确定了2,4-双苯胺嘧啶是CDK4的有效抑制剂。在此，我们描述了该系列的优化。

  DOI：

  10.1016/s0960-894x(03)00203-8

文献信息

• 2,4-Diamino pyrimidine compounds having anti-cell proliferative activity
  申请人：Breault Anne Gloria

  公开号：US20050090493A1

  公开（公告）日：2005-04-28

  A pyrimidine derivative of formula (I) wherein, for example, R 1 is hydrogen, (1-6C)alkyl, (3-5C)alkenyl or (3-5C)alkynyl; Q 1 and Q 2 are independently selected from phenyl, naphthyl, indanyl and 1,2,3,4-tetrahydronaphthyl; and one or both of Q 1 and Q 2 bears on any available carbon atom one substituent of formula (Ia) [provided that when present in Q 1 the substituent of formula (Ia) is not adjacent to the —NH— link]; wherein, for example, X is CH 2 , O, S or NH; Y is H or as defined for Z; Z is OH, SH, NH 2 , (1-4C)alkoxy, (1-4C)alkylthio, —NH(1-4C)alkyl, —N[(1-4C)alkyl] 2 or —NH—(3-8C)cycloalkyl; n is 1, 2 or 3; m is 1, 2 or 3; and Q 1 and Q 2 may optionally bear other substituents selected, for example, from halogeno, (1-6C)alkyl, cyano and (2-4C)alkenyl; or a pharmaceutically-acceptable salt or in-vivo-hydrolysable ester thereof; are useful as anti-cancer agents; and processes for heir manufacture and pharmaceutical compositions containing them are described.

  公式（I）的嘧啶衍生物，其中，例如，R1为氢，（1-6C）烷基，（3-5C）烯基或（3-5C）炔基；Q1和Q2分别选自苯基，萘基，茚基和1,2,3,4-四氢萘基；Q1和/或Q2中的一个或两个在任何可用的碳原子上带有公式（Ia）的取代基[前提是当存在于Q1时，公式（Ia）的取代基不与—NH—连接相邻]；其中，例如，X为CH2，O，S或NH；Y为H或如Z所定义；Z为OH，SH，NH2，（1-4C）烷氧基，（1-4C）烷基硫醚，—NH（1-4C）烷基，—N[(1-4C）烷基]2或—NH—（3-8C）环烷基；n为1, 2或3；m为1, 2或3；Q1和Q2可以选择性地带有其他取代基，例如，卤代，（1-6C）烷基，氰基和（2-4C）烯基；或其药学上可接受的盐或体内水解酯；可用作抗癌剂；并描述了其制备方法和含有它们的药物组合物。
• De novo design approaches targeting an envelope protein pocket to identify small molecules against dengue virus
  作者：Emilse S. Leal、Natalia S. Adler、Gabriela A. Fernández、Leopoldo G. Gebhard、Leandro Battini、Maria G. Aucar、Mariela Videla、María Eugenia Monge、Alejandro Hernández de los Ríos、John Alejandro Acosta Dávila、María L. Morell、Sandra M. Cordo、Cybele C. García、Andrea V. Gamarnik、Claudio N. Cavasotto、Mariela Bollini

  DOI：10.1016/j.ejmech.2019.111628

  日期：2019.11

  the best candidate, from which one synthesized compound displayed micromolar activity. Molecular dynamics-based optimization was performed on this hit, and thirty derivatives were designed in silico, synthesized and evaluated on their capacity to inhibit dengue virus entry into the host cell. Four compounds were found to be potent antiviral compounds in the low-micromolar range. The assessment of drug-like

  登革热是一种由蚊子传播的病毒性疾病，已成为全球主要的公共卫生问题。该疾病具有广泛的临床表现，从轻度感冒样疾病到更严重的出血性登革热和登革热休克综合症。目前，尚无用于治疗该疾病的批准药物或有效疫苗。包膜蛋白（E）是病毒体表面的主要成分。该蛋白在病毒进入过程中起关键作用，构成了抗病毒药物开发的诱人靶标。E蛋白的晶体结构表明存在被洗涤剂正辛基-β-d-葡萄糖苷（β-OG）占据的疏水口袋。该口袋位于结构域I和II之间的铰链区，对于病毒体与宿主细胞融合所需的低pH触发构象重排很重要。针对与E结合并充当病毒进入抑制剂的新型分子的设计，我们通过从头开始在疏水位点（β-OG）内“生长”分子进行了从头设计方法。从产生的24万多个小分子中，选择2,4个嘧啶支架作为最佳候选物，从中一个合成的化合物显示出微摩尔活性。为此，对分子进行了基于分子动力学的优化，并通过计算机设计了三十种衍生物，对其进行了合成并对其抑制登
• Dual targeting of acetylcholinesterase and tau aggregation: Design, synthesis and evaluation of multifunctional deoxyvasicinone analogues for Alzheimer’s disease
  作者：Shoaib Manzoor、Moustafa T. Gabr、Bisma Rasool、Kavita Pal、Nasimul Hoda

  DOI：10.1016/j.bioorg.2021.105354

  日期：2021.11

  have demonstrated remarkable efficiency as potential therapeutics for Alzheimer’s disease (AD). Herein, we reported a new series of deoxyvasicinone analogues as dual inhibitor of acetylcholinesterase (AChE) and tau aggregation that function as multitargeted ligands for AD. All the multitargeted ligands 11(a-j) and 15(a-g) were designed, synthesized, and validated by 1HNMR, 13CNMR and mass spectrometry

  多靶点配体的开发已证明作为阿尔茨海默病 (AD) 的潜在疗法具有显着的效率。在此，我们报道了一系列新的脱氧血管紧张素类似物作为乙酰胆碱酯酶 (AChE) 和 tau 聚集的双重抑制剂，可作为 AD 的多靶点配体。所有多靶点配体11(aj)和15(ag ) 均经过1 HNMR、13 CNMR 和质谱法设计、合成和验证。筛选了所有合成的化合物11(aj)和15(ag ) 抑制 AChE、BACE1、淀粉样蛋白纤维化、α-syn 聚集和 tau 聚集的能力。所有筛选的化合物都对 BACE-1、A β具有弱抑制作用42和 α-syn 聚合。然而，在 AChE 抑制筛选试验和细胞 tau 聚集筛选中，有几种化合物被鉴定为潜在的命中物。在所有化合物中，11f在单剂量筛选 (10 µM) 时显着抑制 AChE 活性和细胞 tau 寡聚化。此外，11f的半数抑制浓度 (IC 50 ) 值分别为 0.91 ±
• 4-Aminoquinoline-Pyrimidine hybrids: Synthesis, antimalarial activity, heme binding and docking studies
  作者：Deepak Kumar、Shabana I. Khan、Babu L. Tekwani、Prija Ponnan、Diwan S. Rawat

  DOI：10.1016/j.ejmech.2014.10.061

  日期：2015.1

  A series of novel 4-aminoquinoline-pyrimidine hybrids has been synthesized and evaluated for their antimalarial activity. Several compounds showed promising in vitro antimalarial activity against both CQ-sensitive and CQ-resistant strains with high selectivity index. All the compounds were found to be nontoxic to the mammalian cell lines. Selected compound 7g exhibited significant suppression of parasitemia in the in vivo assay. The heme binding studies were conducted to determine the mode of action of these hybrid molecules. These compounds form a stable 1:1 complex with hematin suggesting that heme may be one of the possible targets of these hybrids. The interaction of these conjugate hybrids was also investigated by the molecular docking studies in the binding site of PfDHFR. The pharmacokinetic property analysis of best active compounds was also studied using ADMET prediction. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Selective addition of amines to 5-trifluoromethyl-2,4-dichloropyrimidine induced by Lewis acids
  作者：Daniel T. Richter、John C. Kath、Michael J. Luzzio、Nandell Keene、Martin A. Berliner、Matthew D. Wessel

  DOI：10.1016/j.tetlet.2013.06.025

  日期：2013.8

  A variety of 2,4-diamino-pyrimidine systems can be prepared from the corresponding 2,4-dichloropyrimidine by sequential addition of two amines, the first adding selectively to the 4-position. In contrast it was found that 2,4-dichloro-5-trifluoromethyl-pyrimidine yields a 1:1 mixture of the two possible isomers. Lewis acids were employed to increase the ratio of isomers to >10:1 in favor of the 2-addition product. Optimization of the effect of Lewis acid additives on this and other dichloropyrimidine systems will be discussed. (C) 2013 Elsevier Ltd. All rights reserved.