4-methyl Δ²-pyrazoline | 5920-30-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑啉类
• 英文名称: 4-methyl Δ²-pyrazoline
• 英文别名: 4-methyl-4,5-dihydro-1H-pyrazole；4-methyl-2-pyrazoline；4-methyl-4,5-dihydro-1H-pyrazole；4-Methyl-Δ²-pyrazolin；4-Methyl-pyrazolin；4,5-Dihydro-4-methyl-1h-pyrazole
• CAS: 5920-30-9
• 化学式: C₄H₈N₂
• 分子量: 84.1209
• InChiKey: NAFCTXVXMUDIFW-UHFFFAOYSA-N

物化性质

• 沸点：
  142-145 °C(Press: 733 Torr)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  6
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  24.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-methyl Δ²-pyrazoline 生成 4-甲基吡唑
  参考文献：
  名称：

  FISCHER, R.;DOCKNER, T.;ROHR, W.;STROEFER, E.

  摘要：

  DOI：
• 作为产物：
  描述：

  2-甲基丙烯醛 在 肼 作用下， 以 乙腈 为溶剂， 生成 4-methyl Δ²-pyrazoline
  参考文献：
  名称：

  WO2008/34863

  摘要：

  公开号：

文献信息

• Synthesis of adamantane derivatives. LVIII. Reaction of 1-adamantyl chloride with some heterocyclic unsaturated silanes.
  作者：TADASHI SASAKI、AKIRA NAKANISHI、MASATOMI OHNO

  DOI：10.1248/cpb.30.2051

  日期：——

  Various silylated heterocycles having amide functionality were treated with 1-adamantyl chloride (1) in the presence of a Lewis acid to give the corresponding N-adamantylated heterocycles. If α-position to the reacting lactim nitrogen was substituted, the reaction no longer occurred, or the adamantylation occurred at the position other than the expected nitrogen. These facts are attributed to a steric blocking effect of the α-substituent. While the same treatment of the thioamide 46 gave the S-adamantylated product, 48 and 51 afforded in contrast the N- and S-adamantylated products, respectively ; this result can be explained in terms of steric effect. Analogously, silylated 2-pyrazolines and triazoles were adamantylated at nitrogen. The reactions of 2-trimethylsilylthiophene, furan and -pyridine with 1 failed to give site-selective monoadamantylation.

  在路易斯酸存在下，用 1-金刚烷酰氯（1）处理各种具有酰胺官能团的硅烷化杂环，得到相应的 N-金刚烷化杂环。如果反应的内酰胺氮的α位被取代，则不再发生反应，或者在预期氮以外的位置发生金刚烷基化反应。这些情况都归因于 α 取代基的立体阻滞效应。同样处理硫代酰胺 46 得到的是 S-金刚烷化产物，而 48 和 51 则分别得到了 N-和 S-金刚烷化产物；这一结果可以用立体效应来解释。类似地，硅烷化的 2-吡唑和三唑也在氮处发生了金刚烷化。2-三甲基硅基噻吩、呋喃和吡啶与 1 的反应未能产生位点选择性的单金刚烷化反应。
• <i>N</i>′-(Arylsulfonyl)pyrazoline-1-carboxamidines as Novel, Neutral 5-Hydroxytryptamine 6 Receptor (5-HT₆R) Antagonists with Unique Structural Features
  作者：Arnold van Loevezijn、Jennifer Venhorst、Wouter I. Iwema Bakker、Cor G. de Korte、Wouter de Looff、Stefan Verhoog、Jan-Willem van Wees、Martijn van Hoeve、Rob P. van de Woestijne、Martina A. W. van der Neut、Alice J. M. Borst、Maria J. P. van Dongen、Natasja M. W. J. de Bruin、Hiskias G. Keizer、Chris G. Kruse

  DOI：10.1021/jm200466r

  日期：2011.10.27

  The 5-HT6 receptor (5-HT6R) has been in the spotlight for several years regarding CNS-related diseases. We set out to discover novel, neutral 5-HT6R antagonists to improve off-target selectivity compared to basic amine-containing scaffolds dominating the field. High-throughput screening identified the N'-(sulfonyl)pyrazoline-1-carboxamidine scaffold as a promising neutral core for starting hit-to-lead. Medicinal chemistry, molecular modeling, small molecule NMR and X-ray crystallography were subsequently applied to optimize the leads into antagonists (compounds 1-49) displaying high 5-HT6R affinity with optimal off-target selectivity. Unique structural features include a pseudoaromatic system and an internal hydrogen bond freezing the bioactive conformation. While physicochemical properties and CNS availability were generally favorable, significant efforts had to be made to improve metabolic stability. The optimized structure 42 is an extremely selective, hERG-free, high-affinity 5-HT6R antagonist showing good human in vitro metabolic stability. Rat pharrnacokinetic data were sufficiently good to enable further in vivo profiling.
• GAJEWSKI F.; BRZOZOWSKI Z., ACTA POL. PHARM., 1979, 36, NO 1, 33-38
  作者：GAJEWSKI F.、 BRZOZOWSKI Z.

  DOI：——

  日期：——
• KOZAKIEWICZ I.; BRZOZOWSKI Z., ACTA POL. PHARM., 1979, 36, NO 3, 277-282
  作者：KOZAKIEWICZ I.、 BRZOZOWSKI Z.

  DOI：——

  日期：——
• GAJEWSKI F.; BROZOZOWSKI Z., ACTA POL. PHARM., 1979, 36, NO 3, 283-287
  作者：GAJEWSKI F.、 BROZOZOWSKI Z.

  DOI：——

  日期：——