2,4-二氨基-6-甲基-5-嘧啶醇 | 42399-22-4

• 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: 2,4-二氨基-6-甲基-5-嘧啶醇
• 英文名称: 2,4-Diamino-5-hydroxy-6-methylpyrimidin
• 英文别名: 2,4-Diamino-6-methylpyrimidin-5-ol
• CAS: 42399-22-4
• 化学式: C₅H₈N₄O
• mdl: MFCD00160487
• 分子量: 140.145
• InChiKey: CIBJFCTWGISUNT-UHFFFAOYSA-N

物化性质

• 沸点：
  419.4±55.0 °C(Predicted)
• 密度：
  1.472±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  98
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  2,4-二氨基-6-甲基-5-嘧啶醇 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 8-amino-6-methyl-1(10),2-dihydro-pyridazino[4,3-b]pyrimido[4,5-e][1,4]oxazin-3-one
  参考文献：
  名称：

  Synthesis of compounds related to antitumor agents. III. On the additions of acyl halide, dialkyl acetylenedicarboxylate and N-substituted maleimides to 2,4-diamino-5-hydroxy-6-methylpyrimidine.

  摘要：

  2, 4-二氨基-5-羟基-6-甲基嘧啶(I)与酰基卤反应，得到嘧啶并[5, 4-b] [1, 4]恶嗪-6(8H)-酮(IIIa, b)。将乙炔二甲酸二烷基酯与I加成，得到烷氧基羰基亚甲基-嘧啶基[5, 4-b] [1, 4]恶嗪(VI, VII)。从构建哒嗪或呋喃环的证据来看，该化合物的构型被认为是顺式的。类似地，使用马来酰亚胺，获得加合物(XIV)并将其转化为嘧啶并[5, 4-b] [1, 4]恶嗪(XV, XXIa-f)。

  DOI：

  10.1248/cpb.24.1189
• 作为产物：
  描述：

  6-甲基-2,4-嘧啶二胺 在 盐酸 、 sodium hydroxide 、 ammonium peroxydisulfate 作用下， 生成 2,4-二氨基-6-甲基-5-嘧啶醇
  参考文献：
  名称：

  399.嘧啶。第一部分：一些5-羟基嘧啶的合成

  摘要：

  DOI：

  10.1039/jr9560002033

文献信息

• Synthesis of compounds related to antitumor agents. IV. On the reaction of aromatic carboxylates with 2,4-diamino-5-hydroxy-6-methylpyrimidine.
  作者：TETSUO KATO、NORIICHI ODA、ISOO ITO

  DOI：10.1248/cpb.24.2461

  日期：——

  Attempts to prepare oxazolo [4, 5-d] pyrimidines by the reaction of 2, 4-diamino-5-hydroxy-6-methylpyrimidine (I) with aromatic carboxylates. The products were carbinolamines which were converted to oxazolo [4, 5-d] pyrimidines. Also, the application of the Salol reaction of I gave 5-amino-2-(2, 4-diamino-6-methylpyrimidin-5-yl)oxy-2-o-hydroxyphenyl-7-methyl-3H-oxazolo [4, 5-d] pyrimidine (XI) which was an unusual product in this reaction.

  尝试通过2, 4-二氨基-5-羟基-6-甲基嘧啶（I）与芳香羧酸酯反应来合成氮杂环[4, 5-d]嘧啶。产物为碳醇胺，随后转化为氮杂环[4, 5-d]嘧啶。此外，I的Salol反应的应用产生了5-氨基-2-(2, 4-二氨基-6-甲基嘧啶-5-基)氧-2-o-羟基苯基-7-甲基-3H-氮杂环[4, 5-d]嘧啶（XI），这是该反应中一个不寻常的产物。
• Synthesis of compounds related to antitumor agents. V. On the reaction of aliphatic carboxylates with 2,4-diamino-5-hydroxy-6-methylpyrimidine.
  作者：TETSUO KATO、NORIICHI ODA、ISOO ITO

  DOI：10.1248/cpb.25.491

  日期：——

  In a previous paper, we described the reaction of some aromatic carboxylates with 2, 4-diamino-5-hydroxy-6-methylpyrimidine. In continuation with this work, this paper deals with the synthesis of oxazolo [4, 5-d] pyrimidines, pyrimido [5, 4-b] [1, 4] oxazines and pyrimido-[5, 4-b] [1, 4] oxazepines by the reaction of 2, 4-diamino-5-hydroxy-6-methylpyrimidine with aliphatic carboxylates.

  在上一篇论文中，我们介绍了一些芳香族羧酸盐与 2，4-二氨基-5-羟基-6-甲基嘧啶的反应。作为这项工作的延续，本文论述了 2，4-二氨基-5-羟基-6-甲基嘧啶与脂肪族羧酸盐反应合成噁唑并[4，5-d]嘧啶、嘧啶并[5，4-b][1，4]恶嗪和嘧啶并[5，4-b][1，4]恶氮杂卓的过程。
• Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target
  作者：Yongyuth Yuthavong、Bongkoch Tarnchompoo、Tirayut Vilaivan、Penchit Chitnumsub、Sumalee Kamchonwongpaisan、Susan A. Charman、Danielle N. McLennan、Karen L. White、Livia Vivas、Emily Bongard、Chawanee Thongphanchang、Supannee Taweechai、Jarunee Vanichtanankul、Roonglawan Rattanajak、Uthai Arwon、Pascal Fantauzzi、Jirundon Yuvaniyama、William N. Charman、David Matthews

  DOI：10.1073/pnas.1204556109

  日期：2012.10.16

  Malarial dihydrofolate reductase (DHFR) is the target of antifolate antimalarial drugs such as pyrimethamine and cycloguanil, the clinical efficacy of which have been compromised by resistance arising through mutations at various sites on the enzyme. Here, we describe the use of cocrystal structures with inhibitors and substrates, along with efficacy and pharmacokinetic profiling for the design, characterization, and preclinical development of a selective, highly efficacious, and orally available antimalarial drug candidate that potently inhibits both wild-type and clinically relevant mutated forms of Plasmodium falciparum (Pf) DHFR. Important structural characteristics of P218 include pyrimidine side-chain flexibility and a carboxylate group that makes charge-mediated hydrogen bonds with conserved Arg122 (PfDHFR-TS amino acid numbering). An analogous interaction of P218 with human DHFR is disfavored because of three species-dependent amino acid substitutions in the vicinity of the conserved Arg. Thus, P218 binds to the active site of PfDHFR in a substantially different fashion from the human enzyme, which is the basis for its high selectivity. Unlike pyrimethamine, P218 binds both wild-type and mutant PfDHFR in a slow-on/slow-off tight-binding mode, which prolongs the target residence time. P218, when bound to PfDHFR-TS, resides almost entirely within the envelope mapped out by the dihydrofolate substrate, which may make it less susceptible to resistance mutations. The high in vivo efficacy in a SCID mouse model of P. falciparum malaria, good oral bioavailability, favorable enzyme selectivity, and good safety characteristics of P218 make it a potential candidate for further development.

  疟原虫二氢叶酸还原酶（DHFR）是抗叶酸类抗疟药物如嘧啶嗪和环戊鸟苷的靶点，但其临床疗效已因酶上各个位点突变导致耐药性而受到影响。在此，我们描述了利用与抑制剂和底物的共晶结构，以及功效和药代动力学分析进行设计、表征和临床前开发的选择性、高效、口服可用的抗疟药候选药物，可有效抑制野生型和临床相关的突变型疟原虫（Pf）DHFR。 P218的重要结构特征包括嘧啶侧链的灵活性和羧酸基团，它与保守的Arg122（PfDHFR-TS氨基酸编号）形成电荷介导的氢键。P218与人类DHFR的类似相互作用不利于发生，因为在保守的Arg附近存在三个物种特异性氨基酸替换。因此，P218以与人类酶截然不同的方式结合于PfDHFR的活性位点，这是其高选择性的基础。与嘧啶嗪不同，P218以缓慢进入/缓慢离开的紧密结合模式结合于野生型和突变型PfDHFR，这延长了靶点驻留时间。当P218结合于PfDHFR-TS时，几乎完全处于二氢叶酸底物描绘的包络内，这可能使其不易受到耐药突变的影响。P218在SCID小鼠模型中对P. falciparum疟疾的高体内功效、良好的口服生物利用度、有利的酶选择性和良好的安全特性使其成为进一步开发的潜在候选药物。
• Insecticidal 5-substituted-2,4-diaminopyrimidine derivatives
  申请人：FMC Corporation

  公开号：US05627189A1

  公开（公告）日：1997-05-06

  An insecticidal composition comprising, in admixture with an agriculturally acceptable carrier, an insecticidally effective amount of a compound of the formula: ##STR1## wherein R, R.sup.1, R.sup.2, R.sup.3, R.sup.7, R.sup.8, m, n, and p are as defined herein, and agriculturally acceptable salts thereof, and methods of using the same.

  一种杀虫组合物，与农业可接受的载体混合，包含式子的化合物的杀虫有效量：##STR1## 其中R、R.sup.1、R.sup.2、R.sup.3、R.sup.7、R.sup.8、m、n和p如本文所定义，以及其农业可接受的盐，以及使用它们的方法。
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  作者：

  DOI：——

  日期：——