6-morpholinopyridazin-3(2H)-one | 27464-00-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 6-morpholinopyridazin-3(2H)-one
• 英文别名: 6-morpholin-4-yl-2H-pyridazin-3-one；3-morpholin-4-yl-1H-pyridazin-6-one
• CAS: 27464-00-2
• 化学式: C₈H₁₁N₃O₂
• mdl: MFCD15194890
• 分子量: 181.194
• InChiKey: LPUWUXASFUPADF-UHFFFAOYSA-N

物化性质

• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  53.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-morpholinopyridazin-3(2H)-one 在 氯化亚砜 、 乙醇 、 sodium 作用下， 以 氯仿 为溶剂， 反应 7.0h， 生成 2-(2-aminoethylsulfanylmethyl)-6-morpholin-4-ylpyridazin-3-one
  参考文献：
  名称：

  Pyridazinones. 3. Synthesis, antisecretory, and antiulcer activities of 2-cyanoguanidine derivatives

  摘要：

  3(2H)-Pyridazinone derivatives having a 2-cyanoguanidine moiety, as well as a sulfur or an oxygen atom in the alkylene side chain, were synthesized and evaluated for gastric antisecretory and antiulcer activities. The key intermediates, free amines having a thioether linkage, were synthesized by the reaction of 2-(omega-chloroalkyl) derivatives with cysteamine, while other intermediates having an ether linkage were synthesized from 2-(omega-chloroalkyl)oxymethyl derivatives. These free amines were converted via the 3-cyano-2-methyl-1-isothiourea derivatives into the desired 2-cyano-3-substituted-1-guanidine derivatives. All compounds synthesized were evaluated for gastric antisecretory activity in the pylorus-ligated rat by the method of Shay, and selected compounds were evaluated in the stress-induced ulcer test in rat. Structure-activity relationships are discussed. The molecular features for the best activities are a phenyl group in the C-6 position of the 3(2H)-pyridazinone ring, a four-atom chain length between the 3(2H)-pyridazinone ring and the 2-cyanoguanidine moiety, and a thioether rather than an ether linkage. Among them, compound 14, 2-[[[2-(2-cyano-3-methyl-1-guanidino)ethyl]thio]methyl]-6-phenyl-3 (2H)-pyridazinone, had the most potent antisecretory and antiulcer activities. These compounds are neither histamine H2 receptor inhibitors nor anticholinergic agents.

  DOI：

  10.1021/jm00362a011
• 作为产物：
  描述：

  4-(6-氯哒嗪-3-基)吗啉 在 溶剂黄146 作用下， 以95.6 %的产率得到6-morpholinopyridazin-3(2H)-one
  参考文献：
  名称：

  合理设计 PARP1/c-Met 双抑制剂以克服 c-Met 过表达引起的 PARP1 抑制剂耐药性

  摘要：

  PARP1 抑制剂耐药性的出现给当前的治疗带来了挑战，需要开发新的策略来克服这一障碍。本研究描述了一系列针对 PARP1 和 c-Met 的小分子的设计和合成。其中，化合物16被认为是一种高效的双重抑制剂，对PARP1（IC 50 = 3.3 nM）和c-Met（IC 50 = 32.2 nM）表现出优异的抑制活性，并对HR熟练的细胞表现出良好的抗增殖作用。癌细胞系和对 PARP1 抑制剂具有抗性的细胞系。重要的是，在 MDA-MB-231 和 HCT116OR 异种移植模型中，与 PARP1 抑制剂 Olaparib 和 c-Met 抑制剂 Crizotinib（单独或组合）相比，化合物16表现出更优异的抗肿瘤效力。这些发现凸显了 PARP1/c-Met 双抑制剂在扩大 PARP1 抑制剂适应症和克服肿瘤细胞对其耐药性方面的潜力。

  DOI：

  10.1021/acs.jmedchem.4c00077

文献信息

• Synthesis and Biological Evaluation of 2-substituted-6-(morpholinyl/piperidinyl)pyridazin-3(2<i>H</i>)-ones as Potent and Safer Anti-inflammatory and Analgesic Agents
  作者：Jyoti Singh、Deepika Sharma、Ranju Bansal

  DOI：10.1002/jhet.2905

  日期：2017.9

  linyl/piperidinyl)pyridazin‐3(2H)‐ones was synthesized and the structures were established using various spectroscopic techniques. The target compounds were screened for anti‐inflammatory and analgesic activities at 20 and 40 mg/kg. The safety of the synthesized derivatives was evaluated by assessing anti‐platelet activity and ulcer index. The obtained pharmacological data revealed that 6‐morpholinyl

  合成了一系列2-取代6-（吗啉基/哌啶基）哒嗪3（2 H）-one，并使用各种光谱技术建立了结构。筛选目标化合物的抗炎和镇痛活性为20和40 mg / kg。通过评估抗血小板活性和溃疡指数来评估合成衍生物的安全性。获得的药理数据表明，发现6-吗啉基衍生物4a-12a比6-哌啶基衍生物4b-6b效力更高。6-吗啉基取代的哒嗪酮12a具有最大的抗炎和镇痛活性。Homoveratrylamine取代的化合物6a和6b在具有良好的抗炎和止痛活性且无致溃疡性的两个系列中均成为有希望的领先者。与标准药物阿司匹林相比，这两个系列化合物的抗血小板活性结果均显示出血时间明显缩短，表明新的哒嗪酮的心血管安全性。
• Ultraviolet absorbent, photostabilizer, ultraviolet ray-absorbing composition, photostabilized composition and external prepraration for skin
  申请人：Shiseido Co., Ltd.

  公开号：US20030198608A1

  公开（公告）日：2003-10-23

  Providing an ultraviolet absorbent or photostabilizer with excellent absorption over a wide ultraviolet wavelength range and great stability and a high safety profile, as well as an ultraviolet-absorbing composition, a photostabilized composition and an external preparation for skin, where the pyridazine derivative of the following general formula and/or a salt thereof is included as the effective component of the ultraviolet absorbent or photostabilizer, or is included in the ultraviolet-absorbing composition, the photostabilized composition and the external preparation for skin: 1 Wherein R 1 , R 2 , R 3 and R 4 are not simultaneously hydrogen atom; and R 2 and R 3 are not simultaneously morpholino group.

  提供一种具有广泛紫外波长范围内出色吸收和稳定性以及高安全性的紫外线吸收剂或光稳定剂，以及一种紫外线吸收组合物、光稳定组合物和外用皮肤制剂。其中，下列一般式的吡啶嗪衍生物和/或其盐作为紫外线吸收剂或光稳定剂的有效成分，或包含在紫外线吸收组合物、光稳定组合物和外用皮肤制剂中：1其中，R1、R2、R3和R4不同时为氢原子；且R2和R3不同时为吗啡啶基团。
• Ultraviolet absorbent, photostabilizer, ultraviolet ray-absorbing composition, photostabilized composition and external preparation for skin
  申请人：Shiseido Co., Ltd.

  公开号：US06676932B2

  公开（公告）日：2004-01-13

  Providing an ultraviolet absorbent or photostabilizer with excellent absorption over a wide ultraviolet wavelength range and great stability and a high safety profile, as well as an ultraviolet-absorbing composition, a photostabilized composition and an external preparation for skin, where the pyridazine derivative of the following general formula and/or a salt thereof is included as the effective component of the ultraviolet absorbent or photostabilizer, or is included in the ultraviolet-absorbing composition, the photostabilized composition and the external preparation for skin: Wherein R1, R2, R3 and R4 are not simultaneously hydrogen atom; and R2 and R3 are not simultaneously morpholino group.

  提供一种具有在广泛紫外波长范围内优异吸收性和稳定性以及高安全性的紫外线吸收剂或光稳定剂，以及一种紫外线吸收组合物、光稳定组合物和外用皮肤制剂，其中以下通式的吡啶嗪衍生物和/或其盐作为紫外线吸收剂或光稳定剂的有效成分，或包含在紫外线吸收组合物、光稳定组合物和外用皮肤制剂中：其中，R1、R2、R3和R4不同时为氢原子；且R2和R3不同时为吗啉基团。
• Development of a Novel Class of Pyridazinone Derivatives as Selective MAO-B Inhibitors
  作者：Mehmet Abdullah Alagöz、Jong Min Oh、Yaren Nur Zenni、Zeynep Özdemir、Mohamed A. Abdelgawad、Ibrahim A. Naguib、Mohammed M. Ghoneim、Nicola Gambacorta、Orazio Nicolotti、Hoon Kim、Bijo Mathew

  DOI：10.3390/molecules27123801

  日期：——

  Sixteen compounds (TR1–TR16) were synthesized and evaluated for their inhibitory activities against monoamine oxidase A and B (MAOs). Most of the derivatives showed potent and highly selective MAO-B inhibition. Compound TR16 was the most potent inhibitor against MAO-B with an IC50 value of 0.17 μM, followed by TR2 (IC50 = 0.27 μM). TR2 and TR16 selectivity index (SI) values for MAO-B versus MAO-A were

  合成了16 种化合物 ( TR1-TR16 )，并评估了它们对单胺氧化酶 A 和 B (MAO) 的抑制活性。大多数衍生物显示出有效且高度选择性的 MAO-B 抑制作用。化合物TR16是最有效的 MAO-B 抑制剂，IC 50值为 0.17 μM，其次是TR2 (IC 50 = 0.27 μM)。MAO-B 与 MAO-A 的TR2和TR16选择性指数 (SI) 值分别为 84.96 和高于 235.29。与基本结构相比，TR2和TR16中的对氯取代基增加了MAO-B的抑制活性。TR2和TR16是具有竞争力的可逆 MAO-B 抑制剂，K i值分别为 0.230 ± 0.004 和 0.149 ± 0.016 µM。PAMPA 方法表明化合物TR2和TR16具有穿过血脑屏障的趋势。对接研究表明，先导化合物通过与关键以及选择性 E84 或 Y326 残基的结合对 MAO-B 抑制有益，但对主要由疏水接触驱动的相互作用对
• Synthesis, antihypertensive and α-adrenoceptor activity of novel 2-aminoalkyl-3(2H)-pyridazinones
  作者：P Mátyus、J Kosáry、E Kasztreiner、N Makk、E Diesler、K Czakó、G Rabloczky、L Jaszlits、E Horváth、Z Tömösközi、G Cseh、E Horváth、P Arányi

  DOI：10.1016/0223-5234(92)90098-l

  日期：1992.3

  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.