4-氨基甲酰-1-甲基吡啶鎓碘化物 | 5613-08-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 4-氨基甲酰-1-甲基吡啶鎓碘化物
• 英文名称: 4-(aminocarbonyl)-1-methylpyridinium iodide
• 英文别名: 4-Aminocarbonyl-1-methylpyridiniumiodid；1-methyl-4-carbamoylpyridinium iodide；4-carbamido-1-methylpyridinium iodide；isonicotinamide methyl iodide；Isonicotinoyl methiodide；4-carbamoyl-1-methyl-pyridinium; iodide；4-Carbamoyl-1-methylpyridin-1-ium iodide；1-methylpyridin-1-ium-4-carboxamide;iodide
• CAS: 5613-08-1
• 化学式: C₇H₉N₂O*I
• 分子量: 264.066
• InChiKey: PQTCYQMUVMCXKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.39
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-氨基甲酰-1-甲基吡啶鎓碘化物 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 以0.81 g的产率得到1-甲基-1,2,3,6-四氢-4-吡啶甲酰胺
  参考文献：
  名称：

  Carbamyl analogs of potent, nicotinic agonists: pharmacology and computer-assisted molecular modeling study

  摘要：

  To investigate how the substitution of NH2 for CH3 affects the activity of three, potent, semirigid nicotinic agonists, carbamyl analogues were synthesized. The carbamyl agonists were 1-methyl-4-carbamyl-1,2,3,6-tetrahydropyridine methiodide (1), 1-methyl-4-carbamylpiperidine methiodide (2), and 1-methyl-4-carbamylpiperazine methiodide (3). Their potencies (reciprocals of the equipotent molar ratios) at the frog neuromuscular junction with reference to carbamylcholine were 0.77, 0.052, and 0.15, respectively. The acetyl analogues were more potent by factors of 65, 175, and 17, respectively. Explanations for this variable reduction in activity were sought by using computer-assisted molecular mechanics and calculations of electrostatic potential contours. Bioactive conformations of 1-3 were assigned on the basis of a well-supported pharmacophore and the ground-state conformation of the highly potent (50 times that of carbamylcholine) prototype, isoarecolone methiodide (4). Agonist 3 and its acetyl analogue superimposed closely in their ground-state, bioactive conformations, and the differences in their electrostatic potential contours were the least among the three pairs. Accordingly, their potencies differed the least. Agonists 1 and 2 both showed greater differences (with respect to their acetyl analogues) in their electrostatic potential contours and greater differences in potency. Agonist 2, in addition, could achieve the bioactive conformation only at the expense of 2.8 kcal mol-1, and, correspondingly, its activity relative to its acetyl analogue was lowest of all.

  DOI：

  10.1021/jm00122a006
• 作为产物：
  描述：

  4-吡啶甲酰胺 、 碘甲烷 以 乙醇 为溶剂， 反应 0.17h， 以93%的产率得到4-氨基甲酰-1-甲基吡啶鎓碘化物
  参考文献：
  名称：

  A Rapid Microwave Induced Synthesis of Isonicotinamide Derivatives and their Antifungal Activity

  摘要：

  在 10 分钟的快速微波辐照下，通过异烟酰胺与甲基碘和九种不同取代的 2 溴苯乙酮的季铵化反应，制备了十种新型异烟酰胺衍生物。与传统方法相比，微波制备的速度明显更快，产量最高可达 8 倍。通过一维和二维核磁共振、红外光谱、质谱和元素分析确定了合成分子的结构。体外测试了所有化合物在两种不同浓度（10 µg mL-1 和 100 µg mL-1）下对氧孢镰刀菌（Fusarium oxysporum）、枯草镰刀菌（Fusarium culmorum）、巨霉菌（Macrophomina phaseolina）和硬菌（Sclerotinia sclerotiorum）的抗真菌活性。从抗真菌试验中可以看出，大多数制备的化合物对相思豆菌和枯草镰刀菌具有中等到较弱的活性。对 S. sclerotiorum 的抑制率非常高，浓度为 10 µg mL-1 时为 62-87.5%，浓度为 100 µg mL-1 时为 83.7-93.2%。

  DOI：

  10.5562/cca3527

文献信息

• The formation and double decomposition of pyridoxal isonicotinoylhydrazone dimethiodide mediated by iron(II) salts
  作者：Shalom Sarel、Schely Avramovici-Grisaru、Shmuel Cohen

  DOI：10.1039/c39860000047

  日期：——

  Iron(II) ions are shown to induce a hitherto unknown nitrogen-centred metathesis (‘hydrazine metathesis’) of pyridoxal isonicotinoylhydrazone dimethiodide (1) into the symmetrical hydrazine derivatives pyridoxal azine dimethiodide (7) and dimethiodide of bis-isonicotinoyl hydrazide (8) together with isonicotinoylamide methiodide (9) in a ratio 2 : 1 : 1, respectively.

  铁（II）离子显示出诱导了前所未有的氮为中心的复分解吡哆醛isonicotinoylhydrazone dimethiodide（的（“肼复分解”）1）插入对称肼衍生物吡哆醛吖嗪dimethiodide（7）和双-异烟酰肼的dimethiodide（8）分别与异烟酰胺酰胺（9）以2：1：1的比例一起使用。
• Preparation and In Vitro Evaluation of Monoquaternary Inhibitors of Brain Cholinesterases
  作者：Daniel Jun、Martin Paar、Jiri Binder、Jan Marek、Miroslav Pohanka、Petr Stodulka、Kamil Kuca

  DOI：10.2174/157017809789124876

  日期：2009.9.1

  Acetylcholinesterase inhibitors are currently of high interest due to the many reasons. Among them, Alzheimers disease drugs are of great interest. In this study, eleven monoquaternary pyridinium salts substituted by different groups (electron donors and electron acceptors) in position four were prepared. Then, their anticholinesterase activity was tested. As observed, their IC50s ranged from 33 μM to 3981 μM. Moreover, probability of blood-brain barrier penetration was predicted.

  当前，乙酰胆碱酯酶抑制剂受到高度关注，原因有很多。其中，阿尔茨海默病药物尤为引人关注。在这项研究中，制备了十一种在第四位由不同基团（电子供体和电子受体）取代的单季铵吡啶盐。随后，测试了它们的抗胆碱酯酶活性。观察到它们的IC50范围从33 μM到3981 μM。此外，还预测了它们穿透血脑屏障的概率。
• Identification of two metabolites of the cholinesterase reactivator HI-6 isolated from rat urine
  作者：David A Ligtenstein、Eric R J Wils、Simon P Kossen、Albert G Hulst

  DOI：10.1111/j.2042-7158.1987.tb07155.x

  日期：2011.4.12

  Two metabolites, isolated from the urine of rats given the cholinesterase reactivator HI-6 intravenously, still contained quaternary nitrogen atoms and therefore could not be extracted from aqueous solutions by organic solvents. Both metabolites were isolated by preparative high performance liquid chromatography and were identified using mass spectrometry, gas chromatography, infrared spectrometry

  静脉给予胆碱酯酶活化剂HI-6从大鼠尿液中分离出的两种代谢物仍含有季氮原子，因此无法通过有机溶剂从水溶液中提取。通过制备型高效液相色谱法分离这两种代谢物，并使用质谱，气相色谱，红外光谱，紫外光谱和质子核磁共振光谱法进行鉴定。通过化合物的体外制备确认了结构。两种代谢物均含有2-吡啶酮部分。一个具有完整的吡啶鎓-醛肟部分，因此仍具有治疗活性。不变的HI-6与两种确定的代谢物一起排泄并不能提供100％的质量平衡，这表明在大鼠中，
• Umsetzung von N-Alkylpyridinium-Salzen mit Hydroxylamin / Reaction of N-Alkylpyridinium Salts with Hydroxylamine
  作者：Hans Möhrle、Robert Nießen

  DOI：10.1515/znb-2000-0514

  日期：2000.5.1

  1-Methylpyridinium salts showed no reaction with excessive hydroxylamine, but nicotinic acid derivatives in HMPT gave the corresponding N-oxides. 3-Acetyl-1-methylpyridinium iodide generated the hydroximino-pyridine 1-oxide 13 and the isoxazoles 14, 15E, and 15Z. 2- and 4-Cyano-l-methylpyridinium iodides underwent no ring cleavage, but altered only the functional group. However, the 3-cyano compound was converted into the corresponding pyridine N-oxides with carboxamide, hydroxyamidine and carbaldoxime groups.

  1-甲基吡啶盐与过量的羟胺没有反应，但在HMPT中，烟酸衍生物生成了相应的N-氧化物。3-乙酰基-1-甲基吡啶碘化物生成了羟肟吡啶1-氧化物13和异噁唑14、15E和15Z。2-和4-氰基-1-甲基吡啶碘化物没有发生环裂解，但只改变了它们的功能基团。然而，3-氰基化合物与羧酰胺、羟胺和羰基肟基团反应生成了相应的吡啶N-氧化物。
• Carbon-13 NMR characterization of the bispyridinium oximes, toxogonin, HS-3, HS-6 and HI-6
  作者：D. Waysbort、D. Balderman、G. Amitai

  DOI：10.1002/mrc.1270160103

  日期：1981.5

  AbstractThe structure of the bispyridinium oximes, toxogonin, HS‐3, HS‐6 and HI‐6, used as antidotes in organophosphorus poisoning, is confirmed by 13C NMR spectroscopy. The 13C NMR spectra of the corresponding monopyridinium precursors substantiate the signal assignment in the bispyridinium oxime spectra. In all oximes studied the hydroxyiminomethyl group (CHNOH) exists in the syn configuration. The 13C signal differences also readily allow analysis of binary mixtures of the oximes and provide an easy method for monitoring their stability.