4-氨基-6-甲基-2H-吡嗪-3-酮 | 13925-21-8

• 物质功能分类: 医药中间体 - 杂环化合物 - 哒嗪类化合物
• 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-氨基-6-甲基-2H-吡嗪-3-酮
• 英文名称: 3-Hydroxy-4-amino-6-methylpyridazin
• 英文别名: 4-amino-6-methyl-2H-pyridazin-3-one；4-Amino-6-methyl-2H-pyridazin-3-one；5-amino-3-methyl-1H-pyridazin-6-one
• CAS: 13925-21-8
• 化学式: C₅H₇N₃O
• mdl: MFCD00183934
• 分子量: 125.13
• InChiKey: CHXJEGAWOLOLIO-UHFFFAOYSA-N

物化性质

• 熔点：
  268 °C
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  9
• 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：
  67.5
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-氨基-6-甲基-2H-吡嗪-3-酮 在 水 、 3-甲氧基苯甲醛 、 sodium hydroxide 作用下， 以 乙腈 为溶剂， 反应 3.0h， 生成 2-[5-amino-3-methyl-6-oxopyridazin-1(6H)-yl]acetic acid
  参考文献：
  名称：

  2-芳基乙酰胺哒嗪-3(2H)-ones 的进一步研究：作为甲酰肽受体 (FPR) 激动剂的 4,6-二取代类似物的设计、合成和评估

  摘要：

  甲酰肽受体 (FPR) 在调节内源性炎症和免疫中起重要作用。在本研究中，合成了大量在 2 位带有芳基乙酰胺链的哒嗪-3(2 H )-one 衍生物并测试了 FPR 激动剂活性。哒嗪-3(2 H )-one 环被证实是支持 FPR 激动剂活性的合适支架，其在 4 和 6 位的修饰导致鉴定出额外的活性激动剂，从而诱导细胞内 Ca 2+在HL-60 细胞转染了 FPR1、FPR2 或 FPR3。七种甲酰肽受体 1 (FPR1) 特异性和几种混合的 FPR1/FPR2 双激动剂被鉴定为低微摩尔 EC 50值。此外，这些激动剂还激活人类中性粒细胞，诱导细胞内 Ca 2+通量和趋化性。最后，分子对接研究表明，最有效的哒嗪-3(2 H )-ones 分别在 FPR1 和 FPR2 配体结合位点与 fMLF 和 WKYMVM 肽的最佳对接姿势重叠。因此，哒嗪酮类化合物代表了用于进一步开发选择性和/或有效 FPR

  DOI：

  10.1016/j.ejmech.2013.03.066
• 作为产物：
  描述：

  4,5-二氢-6-甲基哒嗪-3(2H)-酮 在 溴 、 一水合肼 、 溶剂黄146 作用下， 反应 22.0h， 生成 4-氨基-6-甲基-2H-吡嗪-3-酮
  参考文献：
  名称：

  Imidazopyridazinones as novel PDE7 inhibitors: SAR and in vivo studies in Parkinson’s disease model

  摘要：

  The synthesis and structure-activity relationship studies of a series of compounds from imidazopyridazinone scaffold as PDE7 inhibitors are disclosed. Potent analogs such as compounds 7 (31 nM), 8 (27 nM), and 9 (12 nM) were identified. The PDE selectivity and pharmacokinetic profile of compounds 7, 8 and 9 are also disclosed. The adequate CNS penetration of compound 7 in mice allowed it to be tested in the MPTP induced PD model and haloperidol induced catalepsy model to probe the differential pharmacology of PDE7 in the striatal pathway. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.07.077

文献信息

• Further Studies on Arylpiperazinyl Alkyl Pyridazinones: Discovery of an Exceptionally Potent, Orally Active, Antinociceptive Agent in Thermally Induced Pain
  作者：Claudio Biancalani、Maria Paola Giovannoni、Stefano Pieretti、Nicoletta Cesari、Alessia Graziano、Claudia Vergelli、Agostino Cilibrizzi、Amalia Di Gianuario、Mariantonella Colucci、Giorgina Mangano、Beatrice Garrone、Lorenzo Polenzani、Vittorio Dal Piaz

  DOI：10.1021/jm900458r

  日期：2009.12.10

  A number of pyridazinone derivatives bearing all arylpiperazinylalkyl chain were synthesized and tested icv in it model of acute nociception induced by thermal stimuli in mice (tail flick). The most interesting and potent compound in this series was 6a, which showed an ED50 = 3.5 mu g, a value about 3-fold higher with respect to morphine by the same route of administration. When administered per os, 6a was 4-fold more potent than morphine in the same test, suggesting it significant bioavailability. The same compound also showed high potency in the hot plate test. The antinociceptive effect of 6a was completely reversed by pretreatment with yohimbine both in the hot plate test and in the tail flick test. This demonstrated the involvement of the adrenergic system, which was confirmed by in vitro radioligand binding studies.
• ——
  作者：S. V. Gres'ko、N. N. Smolyar、Yu. M. Yutilov

  DOI：10.1023/a:1012490919797

  日期：——

  Substituted 2-aryl- and 2-hetarylimidazo[4,5-d]pyridazines were synthesized by oxidative cyclization in the presence of sulfur of 4,5-diamino-6-methylpyridazin-3-one with substituted arene(hetarene)carbaldehydes or heterocyclic compounds having an activated methyl group.
• 2-Arylacetamido-4-phenylamino-5-substituted pyridazinones as formyl peptide receptors agonists
  作者：Claudia Vergelli、Igor A. Schepetkin、Giovanna Ciciani、Agostino Cilibrizzi、Letizia Crocetti、Maria Paola Giovannoni、Gabriella Guerrini、Antonella Iacovone、Liliya N. Kirpotina、Andrei I. Khlebnikov、Richard D. Ye、Mark T. Quinn

  DOI：10.1016/j.bmc.2016.04.019

  日期：2016.6

  N-Formyl peptide receptors (FPRs: FPR1, FPR2, and FPR3) are G protein-coupled receptors that play key roles in modulating immune cells. FPRs represent potentially important therapeutic targets for the development of drugs that could enhance endogenous anti-inflammation systems associated with various pathologies, thereby reducing the progression of inflammatory conditions. Previously, we identified 2-arylacetamide pyridazin-3(2H)-ones as FPR1- or FPR2-selective agonists, as well as a large number of FPR1/FPR2-dual agonists and several mixed-agonists for the three FPR isoforms. Here, we report a new series of 2-arylacetamido-4-aniline pyridazin-3(2H)-ones substituted in position 5 as a further development of these FPR agonists. Chemical manipulation presented in this work resulted in mixed FPR agonists 8a, 13a and 27b, which had EC50 values in nanomolar range. In particular, compound 8a showed a preference for FPR1 (EC50 = 45 nM), while 13a and 27b showed a moderate preference for FPR2 (EC50 = 35 and 61 nM, respectively). Thus, these compounds may represent valuable tools for studying FPR activation and signaling. (C) 2016 Published by Elsevier Ltd.
• COATES, WILLIAM J.;, MCKILLOP ALEXANDER, HETEROCYCLES, 29,(1989) N, C. 1077-1090
  作者：COATES, WILLIAM J.、, MCKILLOP ALEXANDER

  DOI：——

  日期：——
• Further studies on 2-arylacetamide pyridazin-3(2H)-ones: Design, synthesis and evaluation of 4,6-disubstituted analogs as formyl peptide receptors (FPRs) agonists
  作者：Maria Paola Giovannoni、Igor A. Schepetkin、Agostino Cilibrizzi、Letizia Crocetti、Andrei I. Khlebnikov、Claes Dahlgren、Alessia Graziano、Vittorio Dal Piaz、Liliya N. Kirpotina、Serena Zerbinati、Claudia Vergelli、Mark T. Quinn

  DOI：10.1016/j.ejmech.2013.03.066

  日期：2013.6

  Formyl peptide receptors (FPRs) play an essential role in the regulation of endogenous inflammation and immunity. In the present studies, a large series of pyridazin-3(2H)-one derivatives bearing an arylacetamide chain at position 2 was synthesized and tested for FPR agonist activity. The pyridazin-3(2H)-one ring was confirmed to be an appropriate scaffold to support FPR agonist activity, and its modification

  甲酰肽受体 (FPR) 在调节内源性炎症和免疫中起重要作用。在本研究中，合成了大量在 2 位带有芳基乙酰胺链的哒嗪-3(2 H )-one 衍生物并测试了 FPR 激动剂活性。哒嗪-3(2 H )-one 环被证实是支持 FPR 激动剂活性的合适支架，其在 4 和 6 位的修饰导致鉴定出额外的活性激动剂，从而诱导细胞内 Ca 2+在HL-60 细胞转染了 FPR1、FPR2 或 FPR3。七种甲酰肽受体 1 (FPR1) 特异性和几种混合的 FPR1/FPR2 双激动剂被鉴定为低微摩尔 EC 50值。此外，这些激动剂还激活人类中性粒细胞，诱导细胞内 Ca 2+通量和趋化性。最后，分子对接研究表明，最有效的哒嗪-3(2 H )-ones 分别在 FPR1 和 FPR2 配体结合位点与 fMLF 和 WKYMVM 肽的最佳对接姿势重叠。因此，哒嗪酮类化合物代表了用于进一步开发选择性和/或有效 FPR