(R)-N-(4-tert-butylbenzyl)-N-methyl-1-(naphthalen-1-yl)ethanamine | 1200401-05-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (R)-N-(4-tert-butylbenzyl)-N-methyl-1-(naphthalen-1-yl)ethanamine
• 英文别名: (1R)-N-[(4-tert-butylphenyl)methyl]-N-methyl-1-(1-naphthyl)ethanamine；(1R)-N-[(4-tert-butylphenyl)methyl]-N-methyl-1-naphthalen-1-ylethanamine
• CAS: 1200401-05-3
• 化学式: C₂₄H₂₉N
• 分子量: 331.501
• InChiKey: MBFIPZYGAXBFHO-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  (R)-N-(1-(naphthalen-1-yl)ethyl)formamide 在 lithium aluminium tetrahydride 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 5.75h， 生成 (R)-N-(4-tert-butylbenzyl)-N-methyl-1-(naphthalen-1-yl)ethanamine
  参考文献：
  名称：

  Chiral N-benzyl-N-methyl-1-(naphthalen-1-yl)ethanamines and their in vitro antifungal activity against Cryptococcus neoformans, Trichophyton mentagrophytes and Trichophyton rubrum

  摘要：

  In the search for new antifungal compounds and to explore structure activity relationships, a series of 24 chiral benzyl amine type antifungals was synthesised and characterised. In vitro testing against the human pathogen Cryptococcus neoformans revealed that several derivatives had MIC50 values similar to that of the commercial drug Butenafine. All of these contained a bulky group in the para position of the benzyl fragment. Eighteen compounds were also tested for activity against the dermatophytes Trichophyton mentagrophytes and Trichophyton rubrum. Of these (R)-N-(4-tert-butylbenzyI)-N-methyl-1-(naphthalen-1-yl)ethanamine (MIC50,: 0.06 mu g/mL) and a para-benzyloxy substituted derivative (MIC50: 0.125 mu g/mL) possessed high activity. Testing of derivatives with a stereocentre at the benzylic carbon, revealed that (S)-stereochemistry was required for potency: a MIC50 value of 1 mu g/mL was obtained for (S)-1-(4-tert-butylphenyl)-N-methyl-N-(naphthalen-1-ylmethyl)ethanamine. Preparation of the corresponding fluoromethyl compound was achieved employing lipase B from Candida antarctica as catalyst in the key step. A low antifungal activity was observed for the fluorinated derivative indicating the importance of the amine basicity for the antifungal potency of these compounds. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.07.043

文献信息

• Chiral derivatives of Butenafine and Terbinafine: synthesis and antifungal activity
  作者：Erik Fuglseth、Eli Otterholt、Hanne Høgmoen、Eirik Sundby、Colin Charnock、Bård Helge Hoff

  DOI：10.1016/j.tet.2009.09.067

  日期：2009.11

  Two series of allylamines/benzylamines have been synthesised and evaluated for their antifungal activity towards Cryptococcus neoformans. All compounds are chiral derivatives of Butenafine and Terbinafine, having additional substituents at the carbon connected to the central nitrogen atom. In both series. the antifungal activity was strongly dependent on both the steric bulk and the electronic nature of the substituents. Compared to the parent compounds (Butenafine and Terbinafine), the activity was maintained when the hydrogen was replaced with a methyl group. Lower activity was observed for ethyl, whereas introduction of -CH2F, -CHF2, -CF3 or -CN substituents removed all antifungal activity. Testing of (R)- and (S)-N-(4-tert-butylbenzyl)-N-methyl-1-(naphthalen-1-yl)ethanamine against C. neoformans. Cryptococcus diffluens and Trichosporon cutaneum revealed that most of the activity resides in the (R)-enantiomer. The (R)-enantiomer performed as well as, or better (lower MIC values) than Butenafine against each test strain, suggesting that antimycotics based on this compound might be an improvement of existing Butenafine-based formulations. (C) 2009 Elsevier Ltd. All rights reserved.
• Chiral N-benzyl-N-methyl-1-(naphthalen-1-yl)ethanamines and their in vitro antifungal activity against Cryptococcus neoformans, Trichophyton mentagrophytes and Trichophyton rubrum
  作者：Thor H. Krane Thvedt、Kristin Kaasa、Eirik Sundby、Colin Charnock、Bård Helge Hoff

  DOI：10.1016/j.ejmech.2013.07.043

  日期：2013.10

  In the search for new antifungal compounds and to explore structure activity relationships, a series of 24 chiral benzyl amine type antifungals was synthesised and characterised. In vitro testing against the human pathogen Cryptococcus neoformans revealed that several derivatives had MIC50 values similar to that of the commercial drug Butenafine. All of these contained a bulky group in the para position of the benzyl fragment. Eighteen compounds were also tested for activity against the dermatophytes Trichophyton mentagrophytes and Trichophyton rubrum. Of these (R)-N-(4-tert-butylbenzyI)-N-methyl-1-(naphthalen-1-yl)ethanamine (MIC50,: 0.06 mu g/mL) and a para-benzyloxy substituted derivative (MIC50: 0.125 mu g/mL) possessed high activity. Testing of derivatives with a stereocentre at the benzylic carbon, revealed that (S)-stereochemistry was required for potency: a MIC50 value of 1 mu g/mL was obtained for (S)-1-(4-tert-butylphenyl)-N-methyl-N-(naphthalen-1-ylmethyl)ethanamine. Preparation of the corresponding fluoromethyl compound was achieved employing lipase B from Candida antarctica as catalyst in the key step. A low antifungal activity was observed for the fluorinated derivative indicating the importance of the amine basicity for the antifungal potency of these compounds. (C) 2013 Elsevier Masson SAS. All rights reserved.