4-氨基氧基甲基苯酚 | 2089-12-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: 4-氨基氧基甲基苯酚
• 英文名称: O-(4-hydroxylbenzyl)hydroxylamine
• 英文别名: 4-((aminooxy)methyl)phenol；4-Aminooxymethyl-phenol；4-(aminooxymethyl)phenol
• CAS: 2089-12-5
• 化学式: C₇H₉NO₂
• 分子量: 139.154
• InChiKey: QNQWGRLKAXYLKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  55.5
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2922509090

反应信息

• 作为反应物：
  描述：

  4-氨基氧基甲基苯酚 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 O-p-hydroxybenzylhydroxylamine hydrochloride
  参考文献：
  名称：

  O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1

  摘要：

  Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. Recently important advances have been made in understanding IDO1's catalytic mechanism. Although much remains to be discovered, there is strong evidence that the mechanism proceeds through a heme-iron bound alkylperoxy transition or intermediate state. Accordingly, we explored stable structural mimics of the alkylperoxy species and provide evidence that such structures do mimic the alkylperoxy transition or intermediate state. We discovered that O-benzylhydroxylamine, a commercially available compound, is a. potent sub-micromolar inhibitor of IDO1. Structure activity studies of over forty derivatives of O-benzylhydroxylamine led to further improvement in inhibitor potency, particularly with the addition of halogen atoms to the meta position of the aromatic ring. The most potent derivatives and the lead, O-benzylhydroxylamine, have high ligand efficiency values, which are considered an important criterion for successful drug development. Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity. The combination of the simplicity of the structures of these compounds and their excellent cellular activity makes them quite attractive for biological exploration of IDO1 function and antitumor therapeutic applications. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.028
• 作为产物：
  描述：

  对羟基苯甲醇 在 偶氮二甲酸二异丙酯 、 一水合肼 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 4-氨基氧基甲基苯酚
  参考文献：
  名称：

  O-alkylhydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1

  摘要：

  Indoleamine 2,3-dioxygenase-1 (IDO1) is a promising therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. Recently important advances have been made in understanding IDO1's catalytic mechanism. Although much remains to be discovered, there is strong evidence that the mechanism proceeds through a heme-iron bound alkylperoxy transition or intermediate state. Accordingly, we explored stable structural mimics of the alkylperoxy species and provide evidence that such structures do mimic the alkylperoxy transition or intermediate state. We discovered that O-benzylhydroxylamine, a commercially available compound, is a. potent sub-micromolar inhibitor of IDO1. Structure activity studies of over forty derivatives of O-benzylhydroxylamine led to further improvement in inhibitor potency, particularly with the addition of halogen atoms to the meta position of the aromatic ring. The most potent derivatives and the lead, O-benzylhydroxylamine, have high ligand efficiency values, which are considered an important criterion for successful drug development. Notably, two of the most potent compounds demonstrated nanomolar-level cell-based potency and limited toxicity. The combination of the simplicity of the structures of these compounds and their excellent cellular activity makes them quite attractive for biological exploration of IDO1 function and antitumor therapeutic applications. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.028

文献信息

• Preparation of prodrugs for selective drug delivery
  申请人：Mills L. Randell

  公开号：US20050080260A1

  公开（公告）日：2005-04-14

  Synthesis of a chemical compound having the formula A-B-C that may serve for applications such as drug delivery where A is a chemiluminescent, moiety, B is a photochromic moiety, and C is a biologically active moiety where A-B-C may serve as a prodrug. Novel synthetic methods of the present invention to form the prodrug comprised the steps of (1) forming a benzophenone, (2) forming a diaryl ethylene, (3) attaching a phthalimide moiety to at least one of the aryl groups of the ethylene to form a phthalimide-ethylene conjugate, (4) condensing two ethylene-phthalimide conjugates to form a phthalimide-pentadiene conjugate, (5) converting the phthalimide to the phthalhydrazide by reaction with hydrazine to form a carrier compound according to the present invention, and (6) reacting the carrier compound with an nucleophilic moiety of the drug to form the corresponding prodrug. Alternatively the carrier can be prepared by using the halo-substituted diaryl ethylene to make the corresponding cationic leuco dye-like compound with known methods. The cationic compound then is protected by reacting with a nucleophile and coupled with the aminophathalimide by palladium-catalyzed amination to form the protected phthalimide-pentadiene conjugate. The latter is refluxed with hydrazine to convert its phthalimide to the phthalhydrazide and acidified to give the carrier. An additional aspect of the present invention relates to the use of these compounds as antiviral agents for the treatment of viral infections such as HIV and as anticancer agents for the treatment of cancers such as bowel, lung, and breast cancer.

  合成具有A-B-C化学式的化合物，可用于药物传递等应用，其中A是化学发光基团，B是光致变色基团，C是生物活性基团，其中A-B-C可作为前药。本发明的新型合成方法用于形成前药，包括以下步骤：(1)形成苯酮，(2)形成二芳基乙烯，(3)将邻苯二甲酰亚胺基团连接到乙烯的至少一个芳基上，形成邻苯二甲酰亚胺-乙烯共轭物，(4)缩合两个乙烯-邻苯二甲酰亚胺共轭物，形成邻苯二甲酰亚胺-戊二烯共轭物，(5)通过与肼反应将邻苯二甲酰亚胺转化为邻苯二酰肼，形成本发明的载体化合物，(6)将载体化合物与药物的亲核基团反应，形成相应的前药。另外，可以通过使用卤代二芳基乙烯制备相应的阳离子类似的类似类似染料化合物。然后，通过与亲核试剂反应保护阳离子类似化合物，并通过钯催化的胺化与氨基邻苯二甲酰亚胺偶联，形成保护的邻苯二甲酰亚胺-戊二烯共轭物。后者与肼回流，将其邻苯二甲酰亚胺转化为邻苯二酰肼，并酸化以得到载体。本发明的另一个方面涉及将这些化合物用作抗病毒剂，用于治疗病毒感染，如HIV，以及用作抗癌剂，用于治疗结肠癌、肺癌和乳腺癌等癌症。
• [EN] LUMINIDE AND MACROLUMINIDE CLASS OF PHARMACEUTICALS
  申请人：MILLS, Randell, L.

  公开号：WO1989009833A1

  公开（公告）日：1989-10-19

  (EN) A broad class of pharmaceutical agents which react directly with electron carriers or with reactive species produced by electron transport to release a pharmacologically active molecule to effect a therapeutic functional change in the organism by a receptor or nonreceptor mediated action.(FR) On a mis au point une large catégorie d'agents pharmaceutiques réagissant directement avec des porteurs d'électrons ou avec des espèces réactives produites par transport d'électrons, pour libérer une molécule pharmacologiquement active, afin d'effectuer un changement fonctionnel thérapeutique dans l'organisme par une action provoquée par un récepteur ou sans récepteur.

  广泛的药用化学剂，它们直接与电子传递中的电子载体或与其他电子传递中产生的反应性物种相互作用，从而释放活性药物分子，以通过受体或非受体介导的方式在物体中产生治疗作用功能的治疗功能变化。(FR) 已开发并开始应用的一类广泛药物，它们可以直接与电子载体或与其他电子传递中产生的反应性物种相互作用，从而释放活性药物分子，以通过受体或非受体介导的方式在物体中产生治疗功能变化。
• N-Hydroxypiridinedione: A Privileged Heterocycle for Targeting the HBV RNase H
  作者：Dimitrios Moianos、Maria Makri、Georgia-Myrto Prifti、Aristeidis Chiotellis、Alexandros Pappas、Molly E. Woodson、Razia Tajwar、John E. Tavis、Grigoris Zoidis

  DOI：10.3390/molecules29122942

  日期：——

  (HPD) imines that effectively inhibit the HBV RNase H. In our effort to further explore the HPD scaffold, we designed, synthesized, and evaluated 18 novel HPD oximes, as well as 4 structurally related minoxidil derivatives and 2 barbituric acid counterparts. The new analogs were docked on the RNase H active site and all proved able to coordinate the two Mg2+ ions in the catalytic site. All of the new HPDs

  乙型肝炎病毒 （HBV） 仍然是一个全球性的健康威胁。核糖核酸酶 H （RNase H） 是病毒聚合酶蛋白的一部分，在病毒基因组复制过程中切割 pgRNA 模板。抑制 RNase H 活性会阻止 （+） DNA 链合成，并导致非功能性基因组的积累，从而终止病毒复制周期。RNase H 虽然前景广阔，但仍然是针对 HBV 的药物靶点未被充分探索。我们之前报道了一系列有效抑制 HBV RNase H 的 N-羟基吡啶二酮 （HPD） 亚胺的鉴定。在我们进一步探索 HPD 支架的努力中，我们设计、合成和评估了 18 种新型 HPD 肟，以及 4 种结构相关的米诺地尔衍生物和 2 种巴比妥酸对应物。新的类似物对接在 RNase H 活性位点上，并且都被证明能够协调催化位点中的两个 Mg2 + 离子。所有新的 HPD 都有效抑制了细胞检测中的病毒复制，EC50 值在低 μM 范围 （1.1–7.7 μM）
• Design, Synthesis, and Biological Evaluation of Novel Constrained <i>meta</i>-Substituted Phenyl Propanoic Acids as Peroxisome Proliferator-Activated Receptor α and γ Dual Agonists
  作者：Young-Ger Suh、Nam-Jung Kim、Bon-Woong Koo、Kwang-Ok Lee、Sung-Hyun Moon、Dong-Hyung Shin、Jong-Wha Jung、Seung-Mann Paek、Dong-Jo Chang、Funan Li、Hyun-Jin Kang、Tuong Vy Thi Le、Yu Na Chae、Chang Yell Shin、Mi-Kyung Kim、Joong In Lim、Jae-Sang Ryu、Hyun-Ju Park

  DOI：10.1021/jm8003416

  日期：2008.10.23

  In an effort to develop dual PPAR alpha/gamma activators with improved therapeutic efficacy, a series of diaryl alpha-ethoxy propanoic acid compounds comprising two aryl groups linked by rigid oxime ether or isoxazoline ring were designed and synthesized and their biological activities were examined. Most of the compounds possessing an oxime ether linker were more potent PPAR gamma activators than the lead PPAR alpha/gamma dual agonist, tesaglitazar in vitro. Compound 18, one of the derivatives with an oxime ether linker, was found to selectively transactivate PPAR gamma (EC(50) = 0.028 mu M) over PPAR alpha (EC(50) = 7.22 mu M) in vitro and lower blood glucose in db/db mice more than muraglitazar after oral treatment for 11 days.
• EP0414730A4
  申请人：——

  公开号：EP0414730A4

  公开（公告）日：1993-06-16