4-chloro-5-ethyl-2,6-dimethoxypyrimidine | 120268-44-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-chloro-5-ethyl-2,6-dimethoxypyrimidine
• 英文别名: 5-ethyl-6-chloro-2,4-dimethoxypyrimidine；6-chloro-5-ethyl-2,4-dimethoxypyrimidine；4-chloro-5-ethyl-2,6-dimethoxy-pyrimidine；5-ethyl-4-chloro-2,6-dimethoxy-pyrimidine；5-Aethyl-4-chlor-2,6-dimethoxy-pyrimidin
• CAS: 120268-44-2
• 化学式: C₈H₁₁ClN₂O₂
• 分子量: 202.641
• InChiKey: VONNDZOXUOHVCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  13
• 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：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chloro-5-ethyl-2,6-dimethoxypyrimidine 在 盐酸 、 乙醇 、 锌 作用下， 生成 5-乙基尿嘧啶
  参考文献：
  名称：

  v. Merkatz, Chemische Berichte, 1919, vol. 52, p. 876

  摘要：

  DOI：
• 作为产物：
  描述：

  sodium 5-ethylbarbiturate 在 三氯氧磷 作用下， 反应 15.0h， 生成 4-chloro-5-ethyl-2,6-dimethoxypyrimidine
  参考文献：
  名称：

  5,6-Dihydropyrrolo[1,2-c]pyrimidine-1,3(2H,5H)-diones as Annulated Analogues of the Anti-HIV Compound MKC-442 (6-Benzyl-1-(ethoxymethyl)-5-isopropyluracil)

  摘要：

  通过与 Zn/NH4Cl 和 3-溴丙烯反应，从 6-苯甲酰基-5-乙基-2,4-二甲氧基嘧啶（4）合成了抗艾滋病毒化合物 MKC-442 的环状类似物。通过直接或在 O-苄基化后用溴处理，中间的均烯丙基醇会发生闭环反应，生成 5,6-二氢吡咯并[1,2-c]嘧啶酮。无论是环化类似物还是由 4 合成的衍生物，都没有发现对 HIV 的活性。

  DOI：

  10.1055/s-1997-1298

文献信息

• Novel HIV reverse transcriptase inhibitors
  申请人：Guo Hongyan

  公开号：US20080070920A1

  公开（公告）日：2008-03-20

  The invention is related to compounds of Formula (I), (II), or (III): or a pharmaceutically acceptable salt, solvate, ester, and/or phosphonate thereof, compositions containing such compounds, and therapeutic methods that include the administration of such compounds.

  这项发明涉及到以下化合物的公式(I)、(II)或(III)： 或其药用可接受的盐、溶剂化合物、酯和/或膦酸酯，含有这种化合物的组合物，以及包括给予这种化合物的治疗方法。
• Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase
  作者：Radim Nencka、Ivan Votruba、Hubert Hřebabecký、Petr Jansa、Eva Tloušt'ová、Květa Horská、Milena Masojídková、Antonín Holý

  DOI：10.1021/jm070644i

  日期：2007.11.1

  that 6-halouracils substituted at position C5 by certain hydrophobic groups exhibit significant inhibitory activity against this enzyme. The most potent compounds bear a five- or six-membered cyclic substituent containing a pi-electron system at C5 and a chlorine atom attached at C6. 6-Chloro-5-cyclopent-1-en-1-yluracil 7a is the most efficient derivative in this study, with Ki = 0.20 +/- 0.03 microM

  胸苷磷酸化酶在血管生成中起重要作用，这是治疗癌症和其他疾病的有吸引力的靶标。在我们不断努力开发新型胸苷磷酸化酶抑制剂的过程中，我们发现在C5位置被某些疏水基团取代的6-氟尿嘧啶对这种酶表现出显着的抑制活性。最有效的化合物带有一个五元或六元环状取代基，在C5处含有一个π电子系统，在C6处含有一个氯原子。6-氯-5-环戊-1-烯-1-基尿嘧啶7a是这项研究中最有效的衍生物，对于在V79细胞和Ki中表达的胸苷磷酸化酶，Ki = 0.20 +/- 0.03 microM（Ki / dThdKm = 0.0017）从胎盘中纯化的酶为0.29 +/- 0.04 microM（Ki / dThdKm = 0.0024）。
• Synthesis and anti-HIV activity evaluation of 1-[(alkenyl or alkynyl or alkyloxy)methyl]-5-alkyl-6-(1-naphthoyl)-2,4-pyrimidinediones as novel non-nucleoside HIV-1 reverse transcriptase inhibitors
  作者：Lei Ji、Fen-Er Chen、Bin Xie、Erik De Clercq、Jan Balzarini、Christophe Pannecouque

  DOI：10.1016/j.ejmech.2006.09.018

  日期：2007.2

  The synthesis and anti-HIV activity evaluation of a new series of 2,4-pyrimidinediones bearing a 6-(1-naphthoyl) group are described. In general, it was found that most of the title compounds showed good activities against human immunodeficiency virus type-1 (HIV-1). In particular, compound 26 displayed the most potent anti-HIV-1 activity (IC(50)=0.11+/-0.05 microM), inhibiting HIV-1 replication in

  描述了带有6-（1-萘甲酰基）基团的新系列2,4-嘧啶二酮的合成和抗HIV活性评估。通常，发现大多数标题化合物对人免疫缺陷病毒1型（HIV-1）表现出良好的活性。特别是，化合物26显示出最有效的抗HIV-1活性（IC（50）= 0.11 +/- 0.05 microM），比HEPT更有效地抑制MT-4细胞中的HIV-1复制（达45倍），并且DDI（50倍）。
• Synthetic nucleosides and nucleotides. XXVIII. Synthesis of 5-alkylcytidines from 5-alkylbarbituric acids.
  作者：MINEO SANEYOSHI、SHIN'ICHI WATANABE

  DOI：10.1248/cpb.36.2673

  日期：——

  5-Alkylbarbituric acids (1b-f) were converted to 5-alkyl-2, 4, 6-trichloropyrimidines (2b-f) by using phosphoryl chloride in refluxing n-butyl acetate in the presence of N, N-diethylaniline hydrochloride. Treatment of 2 with sodium methoxide in dry acetonitrile followed by reaction with potassium ethyl mercaptide and desulfurization with Raney Ni afforded 5-alkyl-2, 4-dimethoxypyrimidines (5b-f), as key intermediates in the present study. Coupling of 5 with 1-O-acetyl-2, 3, 5-tri-O-benzoyl-β-D-ribofuranose in the presence of stannic chloride in acetonitrile afforded 5-alkyl-1-(2, 3, 5-tri-O-benzoyl)-β-D-ribofuranosyl-1, 2-dihydro-4-methoxypyrimidin-2-ones (6a-f) in quantitative yields. Ammonolysis of 6 with methanolic ammonia afforded the title 5-alkylcytidines (7a-f). Compounds 6 were also easily converted to their uridine counterparts by treatment with hydrochloric acid. Growth-inhibitory effects of 7 on cultured mouse leukemia L5178Y cells, antiviral activity against a rhabdovirus, infectious hematopoietic necrosis virus (IHNV), in cultured CHSE-214 cells and properties as a substrate of human cytidine deaminase were also examined.

  5-烷基巴比妥酸（1b-f）在N,N-二乙基苯胺盐酸盐存在下，使用磷酰氯在回流的正丁基乙酸酯中转化为5-烷基-2,4,6-三氯嘧啶（2b-f）。将2与甲氧基钠在干燥乙腈中处理，随后与乙基硫醇钾反应并在Raney Ni存在下脱硫，得到本研究的关键中间体5-烷基-2,4-二甲氧基嘧啶（5b-f）。在乙腈中锡氯存在下，将5与1-O-乙酰基-2,3,5-三-O-苯甲酰基-β-D-呋喃核糖反应，定量得到5-烷基-1-(2,3,5-三-O-苯甲酰基)-β-D-呋喃核糖基-1,2-二氢-4-甲氧基嘧啶-2-酮（6a-f）。用甲醇氨处理6得到标题5-烷基胞嘧啶核苷（7a-f）。化合物6也很容易通过与盐酸处理转化为相应的尿嘧啶核苷。还研究了7对培养的小鼠白血病L5178Y细胞的生长抑制作用、对培养的CHSE-214细胞中的传染性造血坏死病毒（IHNV）的抗病毒活性以及作为人胞嘧啶脱氨酶底物的性质。
• Synthesis and Anti-HIV Activity of Novel N-1 Side Chain-Modified Analogs of 1-[(2-Hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)
  作者：Renée Pontikis、Rachid Benhida、Anne-Marie Aubertin、David S. Grierson、Claude Monneret

  DOI：10.1021/jm960765a

  日期：1997.6.1

  1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (1, HEPT) were synthesized and evaluated for their anti-HIV-1 activity. In particular, the influence of substitution of the terminal hydroxy group of the acyclic structure of HEPT and the structural rigidity of this side chain were investigated. Halo (7, 8), azido (9), and amino (10-15) derivatives were synthesized from HEPT via the p-tosylate derivative 6. Acylation

  合成了一系列33种N-1的1-[（（2-羟基乙氧基）甲基] -6-（苯硫基）胸腺嘧啶（1，HEPT）的N-1侧链修饰的类似物，并评估了它们的抗HIV-1活性。特别地，研究了HEPT的无环结构的末端羟基的取代和该侧链的结构刚性的影响。经由对甲苯磺酸酯衍生物6由HEPT合成卤代（7、8），叠氮基（9）和氨基（10-15）衍生物。伯胺15的酰化提供了酰胺基类似物16-20。通过在三正丁基膦的存在下使HEPT或6-（2-吡啶硫基）类似物23与二芳基二硫化物反应来制备二芳基衍生物26-29。化合物39-41，其中N-1侧链通过掺入E-构型的双键而硬化，