2-(吗啉-4-基)吡啶-4-甲腈 | 127680-90-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 2-(吗啉-4-基)吡啶-4-甲腈
• 英文名称: 4-morpholinopicolinonitrile
• 英文别名: 2-(morpholin-4-yl)pyridine-4-carbonitrile；2-Pyridinecarbonitrile, 4-(4-morpholinyl)-；4-morpholin-4-ylpyridine-2-carbonitrile
• CAS: 127680-90-4
• 化学式: C₁₀H₁₁N₃O
• 分子量: 189.217
• InChiKey: XXVRMRBHYBYEJW-UHFFFAOYSA-N

物化性质

• 熔点：
  237-238 °C
• 沸点：
  388.3±42.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  49.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(吗啉-4-基)吡啶-4-甲腈 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 反应 4.0h， 生成 4-morpholino-N’-(piperidine-1-carbonothioyl)picolinohydrazonamide
  参考文献：
  名称：

  4-取代的picolinooazonamides作为一类新的潜在抗结核药。

  摘要：

  合成了一系列新的4-取代的吡咯并酰肼酰胺（6-25），并评估了其抑菌活性。在硫代氨基脲链的末端具有亲水环胺的化合物，例如吗啉和吡咯烷，表现出最高的抗分枝杆菌活性。化合物6、11和15（MIC 0.4-0.8μg/ mL）的抗分枝杆菌活性高于参考药物。此外，衍生物15表现出对其他测试微生物如革兰氏阳性，革兰氏阴性或真菌的较低活性。因此，该化合物的特征在于抗微生物活性的选择性。针对人类皮肤成纤维细胞（HDF）和小鼠黑素瘤细胞系（B16-F10）进行的抗增殖研究表明，化合物15的细胞毒性较低。

  DOI：

  10.1016/j.ejmech.2020.112106
• 作为产物：
  描述：

  2-(morpholin-4-yl)pyridine-4-carboxamide 在 三乙胺 、 三氟乙酸酐 作用下， 以 二氯甲烷 为溶剂， 生成 2-(吗啉-4-基)吡啶-4-甲腈
  参考文献：
  名称：

  Lead Optimization of 4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines as A_2A Adenosine Receptor Antagonists for the Treatment of Parkinson’s Disease

  摘要：

  4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-pyrimidines bearing substituted pyridyl groups as C-6 substituents were prepared as selective adenosine hA(2A) receptor antagonists for the treatment of Parkinson's disease. The 5-methoxy-3-pyridyl derivative 6g (hA(2A) K-i 2.3 nM, hA(1) K-i 190 nM) was orally active at 3 mg/kg in a rat HIC model but exposure was poor in nonrodent species, presumably due to poor aqueous solubility. Follow-on compound 16a (hA(2A) K-i 0.83 nM, hA(1) K-i 130 nM), bearing a 6-(morpholin-4-yl)-2-pyridyl substituent at C-6, had improved solubility and was orally efficacious (3 mg/kg, HIC) but showed time-dependent cytochrome P450 3A4 inhibition, possibly related to morpholine ring metabolism. Compound 16j (hA(2A) K-i 0.44 nM, hA(1) K-i 80 nM), bearing a 6-(4-methoxypiperidin-1-yl)-2-pyridyl substituent at C-6, was sparingly soluble but had good oral exposure in rodent and nonrodent species, had no cytochrome P450 or human ether-a-go-go related gene channel issues, and was orally efficacious at 1 mg/kg in HIC and at 3 mg/kg for potentiation Of L-dopa-induced contralateral rotations in 6-hydroxydopamine-lesioned rats.

  DOI：

  10.1021/jm800851u

文献信息

• A study of the photochemically induced reaction of pyridine-2,4-dicarbonitrile with primary and secondary amines. A direct synthesis of aminocyano-pyridines
  作者：Rosanna Bernardi、Tullio Caronna、Sergio Morrocchi、Maurizio Ursini、Bruno M. Vittimberga

  DOI：10.1039/p19900000097

  日期：——

  A novel synthesis of alkylaminopyridinecarbonitriles by a photoinitiated substitution reaction between pyridine-2,4-dicarbonitrile and certain amines is described. The mechanism is discussed.

  描述了通过吡啶-2，4-二甲腈和某些胺之间的光引发的取代反应的烷基氨基吡啶甲腈的新颖合成。讨论了该机制。
• Synthesis and Biological Activity of Piperidinothiosemicarbazones Derived from Aminoazinecarbonitriles
  作者：Dagmara Ziembicka、Katarzyna Gobis、Małgorzata Szczesio、Ewa Augustynowicz-Kopeć、Agnieszka Głogowska、Izabela Korona-Głowniak、Krzysztof Bojanowski

  DOI：10.3390/ph16091267

  日期：——

  significant activity against the standard strain (minimum inhibitory concentration (MIC) 2–4 μg/mL) and even greater activity against the resistant M. tuberculosis strain (MIC 0.5–4 μg/mL). Additionally, the effects of compounds 8–9 were entirely selective (MIC toward other microorganisms ≥ 1000 μg/mL) and non-toxic (IC50 to HaCaT cells 5.8 to >50 μg/mL). The antimycobacterial activity of pyrazine

  为了研究结构修饰如何影响结核抑制效力，我们合成了七种新的哌啶基缩氨基硫酮衍生物8-14，其中三个用吡嗪环取代了吡啶环。衍生物 8-9 和 13-14 对标准菌株表现出显着的活性（最低抑菌浓度 (MIC) 2-4 μg/mL），对耐药结核分枝杆菌菌株表现出更高的活性（MIC 0.5-4 μg/mL）。此外，化合物 8-9 的作用完全具有选择性（对其他微生物的 MIC ≥ 1000 μg/mL）且无毒（对 HaCaT 细胞的 IC50 5.8 至 >50 μg/mL）。吡嗪衍生物 11-12 的抗分枝杆菌活性可以忽略不计（MIC 256 至 >500 μg/mL），表明在这种情况下取​​代芳环通常不是一个有前途的研究方向。使用X射线晶体学测定化合物11的两性离子结构。吸收、分布、代谢和排泄 (ADME) 计算表明，除 11 种之外的所有化合物都可以考虑作为未来药物进行测试。对构效关系进行了分析
• BERNARDI, ROSANNA;CARONNA, TULLIO;MORROCCHI, SERGIO;URSINI, MAURIZIO;VITT+, J. CHEM. SOC. PERKIN TRANS. PT 1,(1990) N, C. 97-100
  作者：BERNARDI, ROSANNA、CARONNA, TULLIO、MORROCCHI, SERGIO、URSINI, MAURIZIO、VITT+

  DOI：——

  日期：——
• Lead Optimization of 4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-6-pyridylpyrimidines as A_2A Adenosine Receptor Antagonists for the Treatment of Parkinson’s Disease
  作者：Xiaohu Zhang、John E. Tellew、Zhiyong Luo、Manisha Moorjani、Emily Lin、Marion C. Lanier、Yongsheng Chen、John P. Williams、John Saunders、Sandra M. Lechner、Stacy Markison、Tanya Joswig、Robert Petroski、Jaime Piercey、William Kargo、Siobhan Malany、Mark Santos、Raymond S. Gross、Jenny Wen、Kayvon Jalali、Zhihong O’Brien、Carol E. Stotz、María I. Crespo、José-Luis Díaz、Deborah H. Slee

  DOI：10.1021/jm800851u

  日期：2008.11.27

  4-Acetylamino-2-(3,5-dimethylpyrazol-1-yl)-pyrimidines bearing substituted pyridyl groups as C-6 substituents were prepared as selective adenosine hA(2A) receptor antagonists for the treatment of Parkinson's disease. The 5-methoxy-3-pyridyl derivative 6g (hA(2A) K-i 2.3 nM, hA(1) K-i 190 nM) was orally active at 3 mg/kg in a rat HIC model but exposure was poor in nonrodent species, presumably due to poor aqueous solubility. Follow-on compound 16a (hA(2A) K-i 0.83 nM, hA(1) K-i 130 nM), bearing a 6-(morpholin-4-yl)-2-pyridyl substituent at C-6, had improved solubility and was orally efficacious (3 mg/kg, HIC) but showed time-dependent cytochrome P450 3A4 inhibition, possibly related to morpholine ring metabolism. Compound 16j (hA(2A) K-i 0.44 nM, hA(1) K-i 80 nM), bearing a 6-(4-methoxypiperidin-1-yl)-2-pyridyl substituent at C-6, was sparingly soluble but had good oral exposure in rodent and nonrodent species, had no cytochrome P450 or human ether-a-go-go related gene channel issues, and was orally efficacious at 1 mg/kg in HIC and at 3 mg/kg for potentiation Of L-dopa-induced contralateral rotations in 6-hydroxydopamine-lesioned rats.
• 4-Substituted picolinohydrazonamides as a new class of potential antitubercular agents
  作者：Malwina Krause、Henryk Foks、Dagmara Ziembicka、Ewa Augustynowicz-Kopeć、Agnieszka Głogowska、Izabela Korona-Głowniak、Krzysztof Bojanowski、Danuta Siluk、Katarzyna Gobis

  DOI：10.1016/j.ejmech.2020.112106

  日期：2020.3

  The series of new 4-substituted picolinohydrazonamides were synthesized (6-25) and evaluated for tuberculostatic activity. Compounds having a hydrophilic cyclic amine such as morpholine and pyrrolidine at the end of the thiosemicarbazide chain, exhibited the highest antimycobacterial activity. The antimycobacterial activity of compounds 6, 11, and 15 (MIC 0.4-0.8 μg/mL) was higher than that of reference

  合成了一系列新的4-取代的吡咯并酰肼酰胺（6-25），并评估了其抑菌活性。在硫代氨基脲链的末端具有亲水环胺的化合物，例如吗啉和吡咯烷，表现出最高的抗分枝杆菌活性。化合物6、11和15（MIC 0.4-0.8μg/ mL）的抗分枝杆菌活性高于参考药物。此外，衍生物15表现出对其他测试微生物如革兰氏阳性，革兰氏阴性或真菌的较低活性。因此，该化合物的特征在于抗微生物活性的选择性。针对人类皮肤成纤维细胞（HDF）和小鼠黑素瘤细胞系（B16-F10）进行的抗增殖研究表明，化合物15的细胞毒性较低。