N-[(4-methoxyphenyl)methyl]-3-(trifluoromethyl)benzamide

• 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-[(4-methoxyphenyl)methyl]-3-(trifluoromethyl)benzamide
• 英文别名: N-(4-methoxybenzyl)-3-(trifluoromethyl)benzamide
• 化学式: C₁₆H₁₄F₃NO₂
• 分子量: 309.288
• InChiKey: SFPBDLWCKYEGNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[(4-methoxyphenyl)methyl]-3-(trifluoromethyl)benzamide 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 100.0 ℃ 、607.99 kPa 条件下， 反应 0.08h， 以77%的产率得到N-[(4-hydroxyphenyl)methyl]-3-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model

  摘要：

  Neuropathic pain is a chronic pain caused by a lesion or disease affecting the somatosensory nervous system. To date, no specific treatment has been developed to cure this pain. Antidepressants and anticonvulsant drugs are used, but they do not demonstrate universal efficacy, and they often cause detrimental adverse effects. Some studies highlighted the efficacy of sildenafil, a well-known inhibitor of phosphodiesterase 5 (PDE5, (IC50=3.3 nM)), in models of pain. Based on these results, we focused our attention on MY 5445, another known PDE5 inhibitor. Homologues, isosteres and structural analogues of MY 5445 were designed and all synthesized compounds were evaluated for their inhibitory activity toward PDE5. Selectivity profiles towards other PDE1-4 isoenzymes, water solubility and stability in acidic medium of the most potent PDE5 inhibitors were determined and the aminophthalazine 16h and its mimetic 41n (3-aminoindazole) were evaluated in comparison to MY 5445 (4b) in vivo in a model of neuropathic pain induced by sciatic nerve cuffing in mice (3 and 0.5 mg/kg, ip twice a day). Both compounds showed the same efficacy on neuropathic allodynia as MY 5445, and thus produced a significant relief of mechanical hypersensitivity after 12 days of treatment. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.026
• 作为产物：
  描述：

  3-三氟甲基苯甲酸 、 4-甲氧基苄胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.25h， 以94%的产率得到N-[(4-methoxyphenyl)methyl]-3-(trifluoromethyl)benzamide
  参考文献：
  名称：

  Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model

  摘要：

  Neuropathic pain is a chronic pain caused by a lesion or disease affecting the somatosensory nervous system. To date, no specific treatment has been developed to cure this pain. Antidepressants and anticonvulsant drugs are used, but they do not demonstrate universal efficacy, and they often cause detrimental adverse effects. Some studies highlighted the efficacy of sildenafil, a well-known inhibitor of phosphodiesterase 5 (PDE5, (IC50=3.3 nM)), in models of pain. Based on these results, we focused our attention on MY 5445, another known PDE5 inhibitor. Homologues, isosteres and structural analogues of MY 5445 were designed and all synthesized compounds were evaluated for their inhibitory activity toward PDE5. Selectivity profiles towards other PDE1-4 isoenzymes, water solubility and stability in acidic medium of the most potent PDE5 inhibitors were determined and the aminophthalazine 16h and its mimetic 41n (3-aminoindazole) were evaluated in comparison to MY 5445 (4b) in vivo in a model of neuropathic pain induced by sciatic nerve cuffing in mice (3 and 0.5 mg/kg, ip twice a day). Both compounds showed the same efficacy on neuropathic allodynia as MY 5445, and thus produced a significant relief of mechanical hypersensitivity after 12 days of treatment. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.026

文献信息

• Chromium(III)-Catalyzed C(sp²)–H Alkynylation, Allylation, and Naphthalenation of Secondary Amides with Trimethylaluminum as Base
  作者：Mengqing Chen、Takahiro Doba、Takenari Sato、Hlib Razumkov、Laurean Ilies、Rui Shang、Eiichi Nakamura

  DOI：10.1021/jacs.0c00127

  日期：2020.3.11

  Stoichiometric and kinetics studies as well as kinetic isotope effects suggest that the catalytic cycle consists of a series of thermally stable but reac-tive intermediates bearing two molecules of the amide substrate on one chromium atom, and also that one of these chro-mate(III) complexs takes part in the alkynylation, allylation, and naphthalenation reactions. The proposed mechanism ac-counts for the

  在用于 CH 活化反应的贱金属中，尽管铬 (III) 具有天然丰度和低毒性，但它却相当未开发。我们在此报告了铬 (III) 催化的芳族和 α,β-不饱和仲酰胺的邻位 C(sp2)-H 官能化，使用容易获得的 AlMe3 作为碱，并使用溴炔、烯丙基溴和 1,4 -dihydro-1,4-epoxynaphthalene 作为亲电试剂。这种在 70-90 °C 下发生的氧化还原中性反应需要低至 1-2 mol% 的 CrCl3 或 Cr(acac)3 作为催化剂，无需添加任何配体，并且可以耐受芳基碘化物、硼酸酯和噻吩基团。化学计量学和动力学研究以及动力学同位素效应表明，催化循环由一系列热稳定但具有反应性的中间体组成，在一个铬原子上带有两个酰胺底物分子，以及这些铬酸盐（III ) 配合物参与炔化、烯丙基化和萘化反应。所提出的机制解释了有效抑制来自 AlMe3 的甲基传递以用于邻位 CH 甲基化。
• Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model
  作者：Maud Bollenbach、Claire Lugnier、Mélanie Kremer、Eric Salvat、Salim Megat、Frédéric Bihel、Jean-Jacques Bourguignon、Michel Barrot、Martine Schmitt

  DOI：10.1016/j.ejmech.2019.05.026

  日期：2019.9

  Neuropathic pain is a chronic pain caused by a lesion or disease affecting the somatosensory nervous system. To date, no specific treatment has been developed to cure this pain. Antidepressants and anticonvulsant drugs are used, but they do not demonstrate universal efficacy, and they often cause detrimental adverse effects. Some studies highlighted the efficacy of sildenafil, a well-known inhibitor of phosphodiesterase 5 (PDE5, (IC50=3.3 nM)), in models of pain. Based on these results, we focused our attention on MY 5445, another known PDE5 inhibitor. Homologues, isosteres and structural analogues of MY 5445 were designed and all synthesized compounds were evaluated for their inhibitory activity toward PDE5. Selectivity profiles towards other PDE1-4 isoenzymes, water solubility and stability in acidic medium of the most potent PDE5 inhibitors were determined and the aminophthalazine 16h and its mimetic 41n (3-aminoindazole) were evaluated in comparison to MY 5445 (4b) in vivo in a model of neuropathic pain induced by sciatic nerve cuffing in mice (3 and 0.5 mg/kg, ip twice a day). Both compounds showed the same efficacy on neuropathic allodynia as MY 5445, and thus produced a significant relief of mechanical hypersensitivity after 12 days of treatment. (C) 2019 Elsevier Masson SAS. All rights reserved.