1-methyl-4-[2-(1-naphthyl)ethenyl]pyridinium iodide | 20144-05-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-methyl-4-[2-(1-naphthyl)ethenyl]pyridinium iodide
• 英文别名: trans-1-[2-(N-methylpyridinium-4-yl)vinyl]naphthalene iodide；1-methyl-4-[(E)-2-(1-naphthalenyl)ethenyl]-pyridinium iodide；trans-1-methyl-4-[2-(1-naphthyl)vinyl]pyridinium iodide；1-methyl-4-[(E)-2-naphthalen-1-ylethenyl]pyridin-1-ium;iodide
• CAS: 20144-05-2
• 化学式: C₁₈H₁₆N*I
• 分子量: 373.236
• InChiKey: JWXOJSQIAOTKFF-RRABGKBLSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.84
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  3.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-methyl-4-[2-(1-naphthyl)ethenyl]pyridinium iodide 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以94%的产率得到1-methyl-4-(1-naphthylvinyl)-1,2,3,6-tetrahydropyridine
  参考文献：
  名称：

  Approaches to protection against nerve agent poisoning. (Naphthylvinyl)pyridine derivatives as potential antidotes

  摘要：

  Analogues of the potent inhibitor of choline acetyltransferase (CAT) (E)-4-(1-naphthylvinyl)pyridine methiodide were synthesized and evaluated for their ability to inhibit CAT and protect against nerve agent intoxication. Several compounds, notably (E)-1-(2-hydroxyethyl)-(1-naphthylvinyl)pyridinium bromide (3), (E)-1-methyl-4-(1-naphthylvinyl)-1,2,3,6-tetrahydropyridine hydrochloride (22), and (E)-1-methyl-4-(1-naphthylvinyl)piperidine hydrochloride (23), were found to afford significant protection against sarin in the mouse and against soman in the guinea pig. However, protection was apparently not related to CAT inhibition. Compound 23, our most effective compound in protecting against nerve agent, was without CAT inhibitory activity. Compound 22, which proved to be a potent CAT inhibitor, most likely owed this activity to being dehydrogenated back to the pyridinium quaternary salt by oxidative enzymes. Several of the (naphthylvinyl)pyridine quaternary salts, but not their tertiary amine analogues, were found to be effective in slowing the rate of aging of soman-inhibited acetylcholinesterase. Ability to slow the rate of aging was enhanced by introduction of methoxy substituents on the aryl moiety whereas the aging rate was actually accelerated by chloro substituents. To date, our most effective compound in slowing the rate of aging, (E)-4-[(4-methoxy-1-naphthyl)vinyl]pyridine methochloride (6), did not provide significant protection against soman in the mouse.

  DOI：

  10.1021/jm00399a022
• 作为产物：
  描述：

  cis-1-[2-(N-methylpyridinium-4-yl)vinyl]naphthalene iodide 在 sodium chloride 、 calf thymus DNA 、 4-羟乙基哌嗪乙磺酸 作用下， 生成 1-methyl-4-[2-(1-naphthyl)ethenyl]pyridinium iodide
  参考文献：
  名称：

  Chudak; Juskowiak, Polish Journal of Chemistry, 2003, vol. 77, # 3, p. 303 - 313

  摘要：

  DOI：

文献信息

• <i>In Situ</i> Assembly of Choline Acetyltransferase Ligands by a Hydrothiolation Reaction Reveals Key Determinants for Inhibitor Design
  作者：Daniel Wiktelius、Anders Allgardsson、Tomas Bergström、Norman Hoster、Christine Akfur、Nina Forsgren、Christian Lejon、Mattias Hedenström、Anna Linusson、Fredrik Ekström

  DOI：10.1002/anie.202011989

  日期：2021.1.11

  tunnel of ChAT and interactions with a hydrophobic pocket near the choline binding site have major implications for the molecular recognition of inhibitors. Our findings clarify the inhibition mechanism of AVPs, establish a drug modality that exploits a target‐catalysed reaction between exogenous and endogenous precursors, and provide new directions for the development of ChAT inhibitors with improved potency

  潜在的药物靶标胆碱乙酰基转移酶（ChAT）催化胆碱能神经元，T细胞和B细胞中神经递质乙酰胆碱的产生。在这里，我们表明，最广泛研究的ChAT抑制剂类芳基乙烯基吡啶（AVPs）在不常见的辅酶A依赖的氢硫基化反应中充当底物。这原位合成产生的加合物是实际的酶抑制剂。加合物深埋在ChAT的活性位点通道中，与胆碱结合位点附近的疏水口袋的相互作用对抑制剂的分子识别具有重要意义。我们的发现阐明了AVP的抑制机制，建立了一种利用外源性和内源性前体之间的靶标催化反应的药物模式，并为开发具有更高效能和生物活性的ChAT抑制剂提供了新的方向。
• peri-Naphthylenediamines: XL. Solvatochromism of 1-methyl-4-[2-(1-naphthyl)ethenyl]pyridinium salts, including that containing “proton sponge” residue
  作者：A. F. Pozharskii、N. V. Vistorobskii、A. A. Bardin、E. A. Filatova

  DOI：10.1134/s1070428006010209

  日期：2006.1

  A number of 1-methyl-4-[2-(1-naphthyl)ethenyl]pyridinium salts were synthesized by condensation of 1,4-dimethylpyridinium iodide with naphthalene-1-carbaldehydes containing dimethylamino groups in positions 4 and 5. The obtained salts are characterized by negative solvatochromism which is the most pronounced for those possessing 1,8-bis(dimethylamino)naphthalene ("proton sponge") and 1,2,2,3-tetramethyl-2,3-di-hydroperimidine residues.
• Structural correlations of choline acetyltransferase inhibitors: trans-N-(carboxymethyl)-4-(.beta.-1-naphthylvinyl)pyridinium bromide and cis-N-(2-aminoethyl)-4-(.beta.-1-naphthylvinyl)-3-methylpyridinium bromide hydrobromide
  作者：Andrew Y. Chweh、John F. DeBernardis、Jerome F. Siuda、Nelson G. Rondan、Jaime E. Abola、Donald J. Abraham

  DOI：10.1021/jm00373a002

  日期：1984.7

  This paper correlates the X-ray structures of two 4-(beta-1-naphthylvinyl)pyridine analogues (one cis and one trans) with chemical and biological activity data for this class of cholineacetylase inhibitors. Our results suggest that one of the two proposed mechanisms for inhibition by this class of compounds better describes their efficacy. Previous arguments about coplanarity of the aromatic rings and nucleophilicty across the vinyl linkage need to be modified. Quantum calculations are also included and substantiate previous suggestions about the charge distribution across the vinyl linkages. An alternate new mechanism of inhibition is proposed to encompass the published data and more recent results discussed in this paper.
• US4006240A
  申请人：——

  公开号：US4006240A

  公开（公告）日：1977-02-01
• Approaches to protection against nerve agent poisoning. (Naphthylvinyl)pyridine derivatives as potential antidotes
  作者：Allan P. Gray、Robert D. Platz、Theresa R. Henderson、Timothy C. P. Chang、Kazuyuki Takahashi、Kenneth L. Dretchen

  DOI：10.1021/jm00399a022

  日期：1988.4

  Analogues of the potent inhibitor of choline acetyltransferase (CAT) (E)-4-(1-naphthylvinyl)pyridine methiodide were synthesized and evaluated for their ability to inhibit CAT and protect against nerve agent intoxication. Several compounds, notably (E)-1-(2-hydroxyethyl)-(1-naphthylvinyl)pyridinium bromide (3), (E)-1-methyl-4-(1-naphthylvinyl)-1,2,3,6-tetrahydropyridine hydrochloride (22), and (E)-1-methyl-4-(1-naphthylvinyl)piperidine hydrochloride (23), were found to afford significant protection against sarin in the mouse and against soman in the guinea pig. However, protection was apparently not related to CAT inhibition. Compound 23, our most effective compound in protecting against nerve agent, was without CAT inhibitory activity. Compound 22, which proved to be a potent CAT inhibitor, most likely owed this activity to being dehydrogenated back to the pyridinium quaternary salt by oxidative enzymes. Several of the (naphthylvinyl)pyridine quaternary salts, but not their tertiary amine analogues, were found to be effective in slowing the rate of aging of soman-inhibited acetylcholinesterase. Ability to slow the rate of aging was enhanced by introduction of methoxy substituents on the aryl moiety whereas the aging rate was actually accelerated by chloro substituents. To date, our most effective compound in slowing the rate of aging, (E)-4-[(4-methoxy-1-naphthyl)vinyl]pyridine methochloride (6), did not provide significant protection against soman in the mouse.