8-methylamino-2-naphthol

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 8-methylamino-2-naphthol
• 英文别名: 8-(Methylamino)-2-naphthol；8-(methylamino)naphthalen-2-ol
• 化学式: C₁₁H₁₁NO
• 分子量: 173.214
• InChiKey: YKFYGLCCTFKKCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-methylamino-2-naphthol 、 4-氯-3-三氟甲基异氰酸苯酯 以 1,4-二氧六环 为溶剂， 反应 3.0h， 生成 3-(4-Chloro-3-(trifluoromethyl)phenyl)-1-(7-hydroxynaphthalen-1-yl)-1-methylurea
  参考文献：
  名称：

  Naphthol derivatives as TRPV1 inhibitors for the treatment of urinary incontinence

  摘要：

  We have identified naphthol derivatives as inhibitors of the vanilloid receptor TRPV1 by high throughput screening. The initial lead showed high clearance in rats and has been optimized by enhancing the acidity of the phenol group. Compound 6b has reduced clearance, improved potency and is active in rat cystometry models of urinary incontinence after intravenous administration. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.013
• 作为产物：
  描述：

  1-氨基-7-萘酚 在 吡啶 、 sodium tetrahydroborate 、 四丁基碘化铵 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 丙酮 为溶剂， 反应 4.0h， 生成 8-methylamino-2-naphthol
  参考文献：
  名称：

  Naphthol derivatives as TRPV1 inhibitors for the treatment of urinary incontinence

  摘要：

  We have identified naphthol derivatives as inhibitors of the vanilloid receptor TRPV1 by high throughput screening. The initial lead showed high clearance in rats and has been optimized by enhancing the acidity of the phenol group. Compound 6b has reduced clearance, improved potency and is active in rat cystometry models of urinary incontinence after intravenous administration. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.013

文献信息

• Non-Biaryl Atropisomers in Organocatalysis
  作者：Sebastian Brandes、Barbara Niess、Marco Bella、Auxiliadora Prieto、Jacob Overgaard、Karl Anker Jørgensen

  DOI：10.1002/chem.200600495

  日期：2006.8.7

  ketone, in up to 93 % ee (ee=enantiomeric excess), as well as for the asymmetric Friedel-Crafts amination of a variety of 2-naphthols, permitting the preparation of the latter in up to 98 % ee. The aminated 8-amino-2-naphthol itself is the first chiral organocatalyst based on non-biaryl atropisomerism. The two enantiomers of this chiral primary amine can be used for the direct alpha-fluorination of alpha-branched

  可以通过简单的胺化步骤制备一种新的6'-羟基金鸡纳生物碱，该类生物碱在喹啉核心的5'位置具有非联芳基阻转异构功能。这些是金鸡纳生物碱经典核心中引入的阻转异构原理的第一批衍生物。胺化的金鸡纳生物碱是有效的有机催化剂，可将高达93％ee（ee =对映体过量）的β-酮酸酯迈克尔加成到丙烯醛和甲基乙烯基酮中，以及各种不对称的Friedel-Crafts胺化反应。 2-萘酚，允许制备高达98％ee的后者。胺化的8-氨基-2-萘酚本身是第一种基于非联芳基阻转异构的手性有机催化剂。该手性伯胺的两种对映异构体可用于α-支化醛的直接α-氟化。氟化化合物因此可以以高达90％ee的浓度进入。
• Organocatalytic Friedel-Crafts Alkylation/Lactonization Reaction of Naphthols with 3-Trifluoroethylidene Oxindoles: The Asymmetric Synthesis of Dihydrocoumarins
  作者：Yun-Long Zhao、Qin-Xin Lou、Long-Sheng Wang、Wen-Hui Hu、Jun-Ling Zhao

  DOI：10.1002/anie.201609390

  日期：2017.1.2

  Naphthols and 3‐trifluoroethylidene oxindoles were found to undergo an asymmetric Friedel–Crafts alkylation/lactonization reaction, catalyzed by only 2.5 mol % of a quinine‐derived squaramide catalyst, to afford the corresponding α‐aryl‐β‐trifluoromethyl dihydrocoumarin derivatives in high yields (up to 99 %) with excellent enantio‐ and diastereoselectivities (up to 98 % ee, >20:1 d.r.). Importantly

  发现萘酚和3-三氟乙叉基吲哚会发生不对称的Friedel-Crafts烷基化/内酯化反应，仅需2.5摩尔％奎宁衍生的方酰胺催化剂即可催化，从而以高收率提供相应的α-芳基-β-三氟甲基二氢香豆素衍生物（高达99％）具有优异的对映异构和非对映异构选择性（高达98％ee，> 20：1 dr）。重要的是，在温和的反应条件下，内酯化是通过在羟吲哚的酰胺基序处萘酚羟基的亲核攻击而进行的。该方案代表了通过有效的分子内酰胺CN键断裂和酯化过程形成二氢香豆素的新策略。
• [EN] NAPHTHYLUREA AND NAPHTHYLACETAMIDE DERIVATIVES AS VANILLOID RECEPTOR 1 (VR1) ANTAGONISTS<br/>[FR] DERIVES AMINES
  申请人：BAYER AG

  公开号：WO2003014064A1

  公开（公告）日：2003-02-20

  Naphthylurea and naphthylacetamide derivatives of formula (I) which have vanilloid receptor 1 (VR1) antagonistic activity are disclosed, formula (I) wherein Y represents formula (II) and formula (III) and the variables Q, X, R6, R7, R8, R8a, R9, R10 and R11 are as defined in the claims. The compounds are useful for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urinary incontinence, overactive bladder, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, incontinence and/or inflammatory disorders.

  本文披露了公式(I)的萘基脲和萘基乙酰胺衍生物，其具有vanilloid受体1（VR1）拮抗活性，其中公式(I)中Y代表公式(II)和公式(III)，而变量Q、X、R6、R7、R8、R8a、R9、R10和R11如权利要求中所定义。这些化合物可用于预防和治疗与VR1活性相关的疾病，特别是用于治疗尿失禁、过度活动膀胱、慢性疼痛、神经病性疼痛、术后疼痛、类风湿性关节炎疼痛、神经痛、神经病、疼痛、神经损伤、缺血、神经退行性疾病、中风、失禁和/或炎症性疾病。
• Amine derivatives
  申请人：——

  公开号：US20040259875A1

  公开（公告）日：2004-12-23

  An amine derivative, its tautomeric or stereoisomeric form, or a salt thereof which has vanilloid receptor 1 (VR1) antagonistic activity, is disclosed. The amine derivative has an excellent activity as VR1 antagonist and useful for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urinary incontinence, overactive bladder, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, incontinence and/or inflammatory disorders.

  本发明揭示了一种具有vanilloid receptor 1（VR1）拮抗活性的胺衍生物、其互变异构体或立体异构体形式或其盐。该胺衍生物具有优异的VR1拮抗活性，适用于预防和治疗与VR1活性相关的疾病，特别是用于治疗尿失禁、过度活动膀胱、慢性疼痛、神经痛、术后疼痛、类风湿性关节炎疼痛、神经痛、神经病、疼痛、神经损伤、缺血、神经退行性疾病、中风、失禁和/或炎症性疾病。
• Chirally Aminated 2-Naphthols—Organocatalytic Synthesis of Non-Biaryl Atropisomers by Asymmetric Friedel–Crafts Amination
  作者：Sebastian Brandes、Marco Bella、Anne Kjærsgaard、Karl Anker Jørgensen

  DOI：10.1002/anie.200503042

  日期：2006.2.6