6-(imidazol-1-yl)pyridazin-3(2H)-one | 110714-14-2

• 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: 6-(imidazol-1-yl)pyridazin-3(2H)-one
• 英文别名: 6-(1-imidazolyl)-3(2H)-pyridazinone；6-(1H-imidazol-1-yl)-2,3-dihydropyridazin-3-one；3-imidazol-1-yl-1H-pyridazin-6-one
• CAS: 110714-14-2
• 化学式: C₇H₆N₄O
• mdl: MFCD14705677
• 分子量: 162.151
• InChiKey: RQOGBYHTYBWDIW-UHFFFAOYSA-N

物化性质

• 熔点：
  239-240 °C
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  59.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(imidazol-1-yl)pyridazin-3(2H)-one 在 palladium on activated charcoal 盐酸 、 氢气 、 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 6-Imidazol-1-yl-2-[2-(2-phenoxyethylamino)ethyl]pyridazin-3-one
  参考文献：
  名称：

  Synthesis, antihypertensive and α-adrenoceptor activity of novel 2-aminoalkyl-3(2H)-pyridazinones

  摘要：

  A number of 2-phenoxyalkylaminoalkyl- and 2-[1,4]benzodioxanylmethylaminoalkyl-3(2H)-pyridazinones were synthesized and tested for hypotensive and antihypertensive activity as well as for alpha-1- and alpha-2-adrenoceptor binding affinities. Some derivatives, eg 5.5, 5.9, 5.12, 6.4 and 6.10, showed strong hypotensive/antihypertensive effect and high affinity for alpha-2- and alpha-1-adrenoceptors. Compound 5.5 was selected for clinical study. In its mode of action a potassium channel opening activity may also be involved.

  DOI：

  10.1016/0223-5234(92)90098-l
• 作为产物：
  描述：

  3-氯-6-(1H-咪唑并L-1-基)哒嗪 在 potassium acetate 作用下， 以 氯仿 、 溶剂黄146 为溶剂， 以55%的产率得到6-(imidazol-1-yl)pyridazin-3(2H)-one
  参考文献：
  名称：

  3(2H)-pyridazinones and pharmaceutical compositions thereof

  摘要：

  本发明涉及一种新的3（2H）-吡啶酮衍生物，其通式为（I），包括含有它们的药物组合物以及它们的制备方法。在通式（I）中，##STR1##代表一个乙基或丙基基团，该基团被末端卤素原子或羟基或NR.sup.1R.sup.2基团取代，其中R.sup.1代表氢原子或未取代或可选择取代的苄基基团；R.sup.2代表氢原子或未取代或可选择取代的苯并[1,4]二噁烷-2-基甲基或-乙基基团或（CH.sub.2）.sub.n--R.sup.3基团，其中n为2或3；而R.sup.3代表未取代或可选择取代的苯氧基或苯硫基团；X代表氢原子或卤素原子或未取代或可选择取代的饱和或不饱和的5-或6-成员杂环基团，其中含有一个氮原子和可选择的另一个杂原子，例如氧、硫或氮原子，但要注意当X代表氢原子或氯原子时，R不同于被羟基或卤素原子末端取代的乙基或丙基基团。通式（I）化合物具有选择性抑制肾上腺素能α.sub.1受体、钙拮抗作用和降低血压的作用。

  公开号：

  US04826845A1

文献信息

• Synthesis and biological affinity of new imidazo- and indol-arylpiperazine derivatives: Further validation of a pharmacophore model for α1-adrenoceptor antagonists
  作者：Giovannella Strappaghetti、Luciano Mastrini、Antonio Lucacchini、Gino Giannaccini、Laura Betti、Laura Fabbrini

  DOI：10.1016/j.bmcl.2008.07.084

  日期：2008.9

  In the continuing search for selective alpha(1)-adrenoceptor (AR) antagonists, new alkoxyarylpiperazinylalkylpyridazinone derivatives were designed and synthesized. The new compounds were tested for their affinity toward alpha(1)-AR, alpha(2)-AR and 5-HT(1A) receptors. The ability of these compounds to inhibit the serotonin transporters (SERT) was also determined. The pharmacological data confirm that

  在继续寻找选择性的α（1）-肾上腺素能受体（AR）拮抗剂时，设计并合成了新的烷氧基芳基哌嗪基烷基吡啶并嗪酮衍生物。测试了新化合物对α（1）-AR，α（2）-AR和5-HT（1A）受体的亲和力。还确定了这些化合物抑制血清素转运蛋白（SERT）的能力。药理学数据证实，增加芳基哌嗪部分的苯环上的邻烷氧基取代基的大小，可使化合物对α（1）-AR的亲和力增强。异丙氧基，评估的最大基团，导致了最佳的alpha（1）-AR亲和力。相反，在邻烷氧基-苯基哌嗪片段内具有酰胺基的化合物对所研究的受体表现出低亲和力。
• α₁-Adrenoceptor Antagonists. 4. Pharmacophore-Based Design, Synthesis, and Biological Evaluation of New Imidazo-, Benzimidazo-, and Indoloarylpiperazine Derivatives
  作者：Laura Betti、Maurizio Botta、Federico Corelli、Monia Floridi、Gino Giannaccini、Laura Maccari、Fabrizio Manetti、Giovannella Strappaghetti、Andrea Tafi、Stefano Corsano

  DOI：10.1021/jm011077g

  日期：2002.8.1

  As a part of a program aimed at discovering compounds endowed with alpha(1)-adrenoceptor (AR) blocking properties, in this paper we describe the synthesis and biological characterization of the compounds designed to fully match a three-dimensional pharmacophore model for alpha(1)-AR antagonists previously developed by our research group. Accordingly, the structure of trazodone (1), identified during

  作为旨在发现具有alpha（1）-肾上腺素受体（AR）阻断特性的化合物的计划的一部分，在本文中，我们描述了旨在完全匹配alpha（1）的三维药效团模型的化合物的合成和生物学表征1）-我们的研究小组先前开发的AR拮抗剂。因此，在通过使用模型作为3D查询执行数据库搜索期间确定的曲唑酮（1）的结构被选为该研究的起点，并根据文献调查的建议进行了修改。特别是将曲唑酮的三唑并吡啶部分替换为不同的杂芳环（例如咪唑，苯并咪唑和吲哚），然后将哒嗪3（2H）-one部分插入新化合物的支架中，以增加分子的总长度，并使其完全适合所有药效团特征。我们的目的还在于研究氯和甲氧基的位置对哌嗪苯环的影响，以及延长或缩短连接苯基哌嗪部分与末端杂环部分的多亚甲基间隔基的影响。通过这种结构优化获得的化合物共有6-（咪唑-1-基）-，6-（苯并咪唑-1-基）-或6-（吲哚-1-基）哒嗪-3（2H）-共同的结构特征，代表芳基哌嗪化
• α1-Adrenoceptor antagonists. rational design, synthesis and biological evaluation of new trazodone-like compounds
  作者：Laura Betti、Maurizio Botta、Federico Corelli、Monia Floridi、Paola Fossa、Gino Giannaccini、Fabrizio Manetti、Giovannella Strappaghetti、Stefano Corsano

  DOI：10.1016/s0960-894x(01)00772-7

  日期：2002.2

  A rational design approach has been applied to synthesize a novel class of compounds with affinity for alpha(1) adrenergic receptors (AR). Molecular structures are characterized by a benzimidazolylpyridazinone or an imidazolylpyridazinone moiety, an original fragment in the field of the arylpiperazine compounds with alpha(1)-AR blocking properties. A 1.1 nM affinity toward alpha(1)-AR was found for compound 3, the most active of this series. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Adenosine receptors: synthesis, structure-activity relationships and biological activity of new 6-amino purine derivatives
  作者：Giovannella Strappaghetti、Stefano Corsano、Roberta Barbaro、Antonio Lucacchini、Gino Giannaccini、Laura Betti

  DOI：10.1016/s0223-5234(98)80050-0

  日期：1998.6

  The synthesis and evaluation of the biological activity of a series of pyridazin-3(2H)-one derivatives is reported. The compounds were tested in radioligand binding assays for affinity at A(1) and A(2A) adenosine receptors in bovine brain cortical membranes, and bovine brain striatal membranes, respectively. None of the compounds shows any affinity towards A(2A) receptor, while compounds in which the 6-chloro-pyridazin-3(2H)-one or 6-phenyl-pyridazin-3(2H)-one group is linked through a chain of two carbon atoms in the 6 position of the adenosine, show a good affinity towards A(1) adenosine receptor, particularly compound 8 in which a phenyl-pyridazinone group is present shows highest affinity with K-i values 6.6 nM. (C) Elsevier, Paris.
• New pyridazinone derivatives as inhibitors of platelet aggregation
  作者：S Corsano、R Vezza、R Scapicchi、S Foresi、G Strappaghetti、GG Nenci、P Gresele

  DOI：10.1016/0223-5234(96)88278-x

  日期：1995.1

  The synthesis and evaluation of the biological activity of a series of 3(2H)-pyridazinone derivatives is reported. We assessed the in vitro activity of these compounds on aggregation and production of thromboxane A(2) and prostaglandin E(2) of human platelets. In compounds 11 and 14 the 3-phenylpropyl group is hr-linked to the 2 position of the pyridazinone ring of 6-(1H-imidazole-1-yl)-3(2H)-pyridazinone 3 or 6-[4-(1H-imidazole-1-yl)-phenyl]-3(2H)-pyridazinone 4, respectively. These compounds inhibited platelet aggregation induced by arachidonic acid, ADP and collagen, and simultaneously suppressed the synthesis of TxA(2) and increased the production of PGE(2). These results characterize compounds 11 and 14 as thromboxane synthase inhibitors. However, the inhibition of platelet aggregation induced by U46619 and of the first wave of ADP-induced aggregation, which is not normally observed with thromboxane synthase inhibitors, suggests additional mechanisms of action for our compounds. On the basis of structural similarities with compounds described previously, these are possibly related to a phosphodiesterase inhibitory activity.