N-(cyclohexyl(phenyl)methyl)formamide | 42071-06-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(cyclohexyl(phenyl)methyl)formamide
• 英文别名: N-[cyclohexyl(phenyl)methyl]formamide
• CAS: 42071-06-7
• 化学式: C₁₄H₁₉NO
• 分子量: 217.311
• InChiKey: FJZJIOMUMBKVIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-(cyclohexyl(phenyl)methyl)formamide 在 N-甲基吗啉 、 盐酸 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.08h， 生成
  参考文献：
  名称：

  Synthesis and structure–activity relationships of potential anticonvulsants based on 2-piperidinecarboxylic acid and related pharmacophores

  摘要：

  Using N-(2,6-dimethyl)phenyl-2-piperidinecarboxamide (1) and N-(alpha -methylbenzyl)-2-piperidinecarboxamide (2) as structural leads, a variety of analogues were synthesised and evaluated for anticonvulsant activity in the MES test in mice. In the N-benzyl series, introduction of 3-Cl, 4-Cl, 3,4-Cl-2, or 3-CF3 groups on the aromatic ring led to an increase in MES activity. Replacement of the alpha -methyl group by either i-Pr or benzyl groups enhanced MES activity with no increase in neurotoxicity. Substitution on the piperidine ring nitrogen led to a decrease in MES activity and neurotoxicity, while reduction of the amide carbonyl led to a complete loss of activity. Movement of the carboxamide group to either the 3- or 4-positions of the piperidine ring decreased MES activity and neurotoxicity. Incorporation of the piperidine ring into a tetrahydroisoquinoline or diazahydrinone nucleus led to increased neurotoxicity. In the N-(2,6-dimethyl)phenyl series, opening of the piperidine ring between the 1- and 6-positions gave the active norleucine derivative 75 (ED50 = 5.8 mg kg(-1), TD50 = 36.4 mg kg(-1), PI = 6.3). Replacement of the piperidine ring of I by cycloalkane (cyclohexane, cyclopentane, and cyclobutane) resulted in compounds with decreased MES activity and neurotoxicity, whereas replacement of the piperidine ring by a 4-pyridyl group led to a retention of MES activity with a comparable PI. Simplification of the 2-piperidinecarboxamide nucleus of 1 into a glycinecarboxamide nucleus led to about a six-fold decrease in MES activity. The 2,6-dimethylanilides were the most potent compounds in the MES test in each group of compounds evaluated, and compounds 50 and 75 should be useful leads in the development of agents for the treatment of tonic-clonic and partial seizures in man. (C) 2001 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)01206-x
• 作为产物：
  描述：

  硝基环己烷 在 偶氮二异丁腈 、 三正丁基氢锡 、 sodium hydride 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 1.75h， 生成 N-(cyclohexyl(phenyl)methyl)formamide
  参考文献：
  名称：

  Aza-Henry reaction of substituted nitroalkanes using α-formamidoaryl sulfones as N-acylimino equivalents

  摘要：

  Base-promoted elimination of p-toluenesulfinic acid from N-formamidoaryl sulfones leads to the corresponding N-acylimines that react with primary and secondary nitronate anions giving anti-beta-formamido nitroderivatives in good yields and high diastereoselectivity. (c) 2006 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tetlet.2006.03.114

文献信息

• Discovery of Novel Acetamide-Based Heme Oxygenase-1 Inhibitors with Potent <i>In Vitro</i> Antiproliferative Activity
  作者：Antonino N. Fallica、Valeria Sorrenti、Agata G. D’Amico、Loredana Salerno、Giuseppe Romeo、Sebastiano Intagliata、Valeria Consoli、Giuseppe Floresta、Antonio Rescifina、Velia D’Agata、Luca Vanella、Valeria Pittalà

  DOI：10.1021/acs.jmedchem.1c00633

  日期：2021.9.23

  promotes heme catabolism exercising cytoprotective roles in normal and cancer cells. Herein, we report the design, synthesis, molecular modeling, and biological evaluation of novel HO-1 inhibitors. Specifically, an amide linker in the central spacer and an imidazole were fixed, and the hydrophobic moiety required by the pharmacophore was largely modified. In many tumors, overexpression of HO-1 correlates

  血红素加氧酶-1 (HO-1) 促进血红素分解代谢，在正常细胞和癌细胞中发挥细胞保护作用。在此，我们报告了新型 HO-1 抑制剂的设计、合成、分子建模和生物学评价。具体来说，固定了中心间隔基中的酰胺连接体和咪唑，并对药效团所需的疏水部分进行了很大程度的修饰。在许多肿瘤中，HO-1 的过度表达与不良预后和化疗耐药相关，表明抑制 HO-1 作为一种可能的抗肿瘤策略。因此，化合物7i和7l – p因其对抗 HO-1 的效力而出现，并研究了它们对前列腺 (DU145)、肺癌 (A549) 和胶质母细胞瘤 (U87MG、A172) 癌细胞的抗癌活性。所选化合物对 U87MG 细胞表现出最佳活性。进一步研究了化合物7l的细胞内酶HO-1活性、表达水平以及对细胞侵袭和血管内皮生长因子(VEGF)胞外释放的影响。获得的数据表明7l可以通过调节HO-1表达来降低细胞侵袭性。
• Cervinka,O.; Fusek,J., Collection of Czechoslovak Chemical Communications, 1973, vol. 38, p. 441 - 446
  作者：Cervinka,O.、Fusek,J.

  DOI：——

  日期：——
• [DE] SUBSTITUIERTE 1-ARYL-CYCLOPROPYLMETHYLAMINO-1,3,5-TRIAZINE<br/>[EN] SUBSTITUTED 1-ARYL-CYCLOPROPYLMETHYLAMINO-1,3,5-TRIAZINES<br/>[FR] 1-ARYL-CYCLOPROPYLMETHYLAMINO-1,3,5-TRIAZINES SUBSTITUEES
  申请人：BAYER AG

  公开号：WO2001068616A1

  公开（公告）日：2001-09-20

  Die Erfindung betrifft neue, substituierte 1-Aryl-cyclopropylamino-1,3,5-triazine der allgemeinen Formel (I), in welcher die Reste R?1, R2, R3¿ und Ar, die in der Beschreibung angegebene Bedeutung haben, ein Verfahren und Zwischenprodukte zu ihrer Herstellung und ihre Verwendung als Herbizide und Insektizide.
• Aza-Henry reaction of substituted nitroalkanes using α-formamidoaryl sulfones as N-acylimino equivalents
  作者：Marino Petrini、Elisabetta Torregiani

  DOI：10.1016/j.tetlet.2006.03.114

  日期：2006.5

  Base-promoted elimination of p-toluenesulfinic acid from N-formamidoaryl sulfones leads to the corresponding N-acylimines that react with primary and secondary nitronate anions giving anti-beta-formamido nitroderivatives in good yields and high diastereoselectivity. (c) 2006 Published by Elsevier Ltd.
• Synthesis and structure–activity relationships of potential anticonvulsants based on 2-piperidinecarboxylic acid and related pharmacophores
  作者：Bin Ho、A Michael Crider、James P Stables

  DOI：10.1016/s0223-5234(00)01206-x

  日期：2001.3

  Using N-(2,6-dimethyl)phenyl-2-piperidinecarboxamide (1) and N-(alpha -methylbenzyl)-2-piperidinecarboxamide (2) as structural leads, a variety of analogues were synthesised and evaluated for anticonvulsant activity in the MES test in mice. In the N-benzyl series, introduction of 3-Cl, 4-Cl, 3,4-Cl-2, or 3-CF3 groups on the aromatic ring led to an increase in MES activity. Replacement of the alpha -methyl group by either i-Pr or benzyl groups enhanced MES activity with no increase in neurotoxicity. Substitution on the piperidine ring nitrogen led to a decrease in MES activity and neurotoxicity, while reduction of the amide carbonyl led to a complete loss of activity. Movement of the carboxamide group to either the 3- or 4-positions of the piperidine ring decreased MES activity and neurotoxicity. Incorporation of the piperidine ring into a tetrahydroisoquinoline or diazahydrinone nucleus led to increased neurotoxicity. In the N-(2,6-dimethyl)phenyl series, opening of the piperidine ring between the 1- and 6-positions gave the active norleucine derivative 75 (ED50 = 5.8 mg kg(-1), TD50 = 36.4 mg kg(-1), PI = 6.3). Replacement of the piperidine ring of I by cycloalkane (cyclohexane, cyclopentane, and cyclobutane) resulted in compounds with decreased MES activity and neurotoxicity, whereas replacement of the piperidine ring by a 4-pyridyl group led to a retention of MES activity with a comparable PI. Simplification of the 2-piperidinecarboxamide nucleus of 1 into a glycinecarboxamide nucleus led to about a six-fold decrease in MES activity. The 2,6-dimethylanilides were the most potent compounds in the MES test in each group of compounds evaluated, and compounds 50 and 75 should be useful leads in the development of agents for the treatment of tonic-clonic and partial seizures in man. (C) 2001 Editions scientifiques et medicales Elsevier SAS.