5-乙酰基-4-氨基-6-甲基-2H-吡嗪-3-酮 | 17335-04-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 5-乙酰基-4-氨基-6-甲基-2H-吡嗪-3-酮
• 英文名称: 5-Acetyl-4-amino-6-methyl-pyridazin-3-on
• 英文别名: 5-acetyl-4-amino-6-methyl-2H-pyridazin-3-one；5-Acetyl-4-amino-6-methylpyridazin-3(2H)-one；4-acetyl-5-amino-3-methyl-1H-pyridazin-6-one
• CAS: 17335-04-5
• 化学式: C₇H₉N₃O₂
• mdl: MFCD03093605
• 分子量: 167.167
• InChiKey: NYBIMOVPQNHKJH-UHFFFAOYSA-N

物化性质

• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.285
• 拓扑面积：
  84.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	5-acetyl-4-amino-2-(2-bromoethyl)-6-methylpyridazin-3(2H)-one	1192490-67-7	C9H12BrN3O2	274.117
  ——	5-acetyl-4-amino-2-(3-bromopropyl)-6-methylpyridazin-3(2H)-one	1192490-68-8	C10H14BrN3O2	288.144
  ——	ethyl 2-[4-acetyl-5-amino-3-methyl-6-oxopyridazin-1(6H)-yl]acetate	1027173-11-0	C11H15N3O4	253.258
  ——	5-acetyl-4-amino-6-methyl-2-[3-(4-p-tolylpiperazin-1-yl)propyl]pyridazin-3(2H)-one	1192490-69-9	C21H29N5O2	383.494
  ——	5-acetyl-4-amino-2-{3-[4-(4-chlorophenyl)piperazin-1-yl]propyl}-6-methylpyridazin-3(2H)-one	1192490-71-3	C20H26ClN5O2	403.912
  ——	5-acetyl-4-amino-6-methyl-2-{3-[4-(3-methylphenyl)piperazin-1-yl]propyl}pyridazin-3(2H)-one	1192490-73-5	C21H29N5O2	383.494
  ——	5-acetyl-4-amino-2-{3-[4-(4-methoxyphenyl)piperazin-1-yl]propyl}-6-methylpyridazin-3(2H)-one	1192490-70-2	C21H29N5O3	399.493
  ——	5-acetyl-4-amino-2-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}-6-methylpyridazin-3(2H)-one	1026842-10-3	C20H26ClN5O2	403.912
  ——	5-acetyl-4-amino-2-{3-[4-(3-methoxyphenyl)piperazin-1-yl]propyl}-6-methylpyridazin-3(2H)-one	1192490-72-4	C21H29N5O3	399.493
  ——	5-acetyl-4-amino-6-methyl-2-[3-oxo-3-(4-p-tolylpiperazin-1-yl)propyl]pyridazin-3(2H)-one	1192490-39-3	C21H27N5O3	397.477

反应信息

• 作为反应物：
  描述：

  5-乙酰基-4-氨基-6-甲基-2H-吡嗪-3-酮 在 水 、 copper diacetate 、 三乙胺 、 3-甲氧基苯甲醛 、 sodium hydroxide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 15.0h， 生成 2-[4-acetyl-5-(4-methoxyphenylamino)-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：

  3,4-二甲基-6H-异噁唑并[3,4-d]哒嗪-7-酮 在 palladium on activated charcoal 一水合肼 作用下， 以 乙醇 为溶剂， 生成 5-乙酰基-4-氨基-6-甲基-2H-吡嗪-3-酮
  参考文献：
  名称：

  异恶唑-[3,4-d]-哒嗪-7-（6H）-作为新型醛糖还原酶抑制剂的潜在底物。

  摘要：

  异恶唑-[3,4-d]-哒嗪-7-（6H）-一（2）及其相应的开放衍生物5-乙酰基-4-氨基-（4-硝基）-6-取代的3（2H）相对于先前报道的5，6-二氢苯并[h] cinnolin-3（2H）one-2乙酸（1），哒嗪酮（3，4）被用作合成新的醛糖还原酶抑制剂的简化底物。此外，制备了一些缺少5-乙酰基的衍生物。衍生自2的几种化合物具有与索比尼尔相当的抑制特性。在这一类中，带有吸电子取代基的苯基在6位上的存在被证明是有益的，而与它在环上的位置（5g，jl）无关。乙酸衍生物比丙酸和丁酸类似物更有效。相反，所有的单环化合物（6-8）都是无活性的或仅是弱活性的。还研究了3-甲基-4-（对氯苯基）异唑并-[3,4-d]-哒嗪-7-（6H）-一乙酸（5g），它是最有效的衍生物。分子建模研究，以评估与模型1在与酶的相互作用中可能存在的相似性。

  DOI：

  10.1021/jm981107o

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.
• Synthesis of five and six-membered heterocycles bearing an arylpiperazinylalkyl side chain as orally active antinociceptive agents
  作者：Claudia Vergelli、Giovanna Ciciani、Agostino Cilibrizzi、Letizia Crocetti、Lorenzo Di Cesare Mannelli、Carla Ghelardini、Gabriella Guerrini、Antonella Iacovone、Maria Paola Giovannoni

  DOI：10.1016/j.bmc.2015.08.043

  日期：2015.10

  A number of heterocycles bearing an arylpiperazinylalkyl side chain and structurally related to the previously described lead ET1 (4-amino-6-methyl-2-[3-(4-p-tolylpiperazin-1-yl) propyl]-5-vinylpyridazin-3 (2H)-one) was synthesized and tested for their antinociceptive activity in Writhing Test. Many compounds, tested at doses of 20-40 mg/kg po were able to reduce the number of abdominal constrictions by more than 47% and, in same cases, the potency is comparable to lead ET1 as for 5e, 24a, 27b and 27c. The analgesia induced by the active compounds was completely prevented by pretreatment with alpha(2)-antagonist yohimbine, confirming the involvement of the adrenergic system in the mechanism of action for these new compounds. (C) 2015 Elsevier Ltd. All rights reserved.
• 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.