2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)acetohydrazide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)acetohydrazide
• 英文别名: 4-[(hydrazinocarbonyl)methyl]-7-benzyloxy-2H-chromen-2-one；2-(2-oxo-7-phenylmethoxychromen-4-yl)acetohydrazide
• 化学式: C₁₈H₁₆N₂O₄
• 分子量: 324.336
• InChiKey: PJSYGKQEHALGAK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  90.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)acetohydrazide 在 sodium acetate 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 60.0h， 生成 2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)-N-(2-methylimino-4-phenylthiazol-3(2H)-yl)acetamide
  参考文献：
  名称：

  作为阿尔茨海默病潜在乙酰胆碱酯酶抑制剂的新型香豆素衍生物的设计和合成

  摘要：

  用各种生物活性化学片段合成了 20 种新型 7-苄氧基香豆素类化合物。合成的化合物显示出显着的乙酰胆碱酯酶 (AChE) 抑制活性。体外实验表明化合物 7-benzyloxy-4-{[(4-phenylthiazol-2(3H)-ylidene)hydrazono]methyl}-2H-chromen-2-one ( 5b , IC 50 = 0.451μM), 7-benzyloxy-4-({[4-(4-甲氧基苯基)thiazol-2(3H)-ylidene]hydrazono}methyl)-2H-chromen-2-one ( 5d, IC 50 = 0.625μM), 5-amino-1-[2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)acetyl]-1H-pyrazole-4-carbonitrile ( 13c , IC 50 = 0.466μM),

  DOI：

  10.1016/j.bioorg.2021.104792
• 作为产物：
  描述：

  7-羟基香豆素-4-乙酸 在 硫酸 、 potassium carbonate 、 一水合肼 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 50.0h， 生成 2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)acetohydrazide
  参考文献：
  名称：

  作为阿尔茨海默病潜在乙酰胆碱酯酶抑制剂的新型香豆素衍生物的设计和合成

  摘要：

  用各种生物活性化学片段合成了 20 种新型 7-苄氧基香豆素类化合物。合成的化合物显示出显着的乙酰胆碱酯酶 (AChE) 抑制活性。体外实验表明化合物 7-benzyloxy-4-{[(4-phenylthiazol-2(3H)-ylidene)hydrazono]methyl}-2H-chromen-2-one ( 5b , IC 50 = 0.451μM), 7-benzyloxy-4-({[4-(4-甲氧基苯基)thiazol-2(3H)-ylidene]hydrazono}methyl)-2H-chromen-2-one ( 5d, IC 50 = 0.625μM), 5-amino-1-[2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)acetyl]-1H-pyrazole-4-carbonitrile ( 13c , IC 50 = 0.466μM),

  DOI：

  10.1016/j.bioorg.2021.104792

文献信息

• Substituted Aminoalkyl- and Amidoalkyl-Benzopyran Derivatives
  申请人：Carotti Angelo

  公开号：US20090005436A1

  公开（公告）日：2009-01-01

  This invention is related to novel aminoalkyl- and amidoalkyl-benzopyran derivatives of the following general formula (I) wherein: the group is a substituent in position 6 or 7 wherein: R is an aromatic mono- or bi-cyclic carbocyclic ring or a mono- or bi-cyclic heterocyclic ring radical, said rings being optionally substituted by one or two substituents selected from (C 1 -C 5 ) straight or branched alkyl, (C 1 -C 5 ) straight or branched alkoxy, hydroxy, halogen and trifluoromethyl; m is zero or an integer from 1 to 3; n, p, R 1 and R 2 are as herein indicated and R 3 and R 4 are both hydrogen or taken together represent an oxygen atom, and the pharmaceutically acceptable salts thereof. The compounds that are active as selective and reversible MAO-B inhibitors in vitro and in vivo, are useful as medicaments for the prevention and the treatment of CNS degenerative disorders.

  本发明涉及以下通式（I）的新型氨基烷基和酰胺烷基苯并吡喃衍生物： 其中：基团是6或7位的取代基，其中：R是芳香单环或双环碳环或单环或双环杂环基团，所述环可以选择地由一或两个取代基取代，所述取代基选择自（C1-C5）直链或支链烷基，（C1-C5）直链或支链烷氧基，羟基，卤素和三氟甲基；m为零或1至3的整数；n、p、R1和R2如本文所示，而R3和R4均为氢或一起代表氧原子，以及其药学上可接受的盐。 这些化合物在体外和体内作为选择性和可逆的MAO-B抑制剂具有活性，可用作预防和治疗中枢神经系统退行性疾病的药物。
• Discovery of a Novel Class of Potent Coumarin Monoamine Oxidase B Inhibitors: Development and Biopharmacological Profiling of 7-[(3-Chlorobenzyl)oxy]-4-[(methylamino)methyl]-2<i>H</i>-chromen-2-one Methanesulfonate (NW-1772) as a Highly Potent, Selective, Reversible, and Orally Active Monoamine Oxidase B Inhibitor
  作者：Leonardo Pisani、Giovanni Muncipinto、Teresa Fabiola Miscioscia、Orazio Nicolotti、Francesco Leonetti、Marco Catto、Carla Caccia、Patricia Salvati、Ramon Soto-Otero、Estefania Mendez-Alvarez、Celine Passeleu、Angelo Carotti

  DOI：10.1021/jm9010127

  日期：2009.11.12

  In an effort to discover novel selective monoamine oxidase (MAO) B inhibitors with favorable physicochemical and pharmacokinetic profiles, 7-[m-halogeno)benzyloxy]coumarins bearing properly selected polar substituents at position 4 were designed, synthesized, and evaluated as MAO inhibitors. Several compounds with MAO-B inhibitory activity in the nanomolar range and excellent MAO-B selectivity (selectivity index SI > 400) were identified. Structure-affinity relationships and docking simulations provided valuable insights into the enzyme-inhibitor binding interactions at position 4, which has been poorly explored. Furthermore, computational and experimental studies led to the identification and biopharmacological characterization of 7-[(3-chlorobenzyl)oxy]-4-[(methylamino)methyl]-2H-chromen-2-one methanesulfonate 22b (NW-1772) as an in vitro and in vivo potent and selective MAO-B inhibitor, with rapid blood-brain barrier penetration, short-acting and reversible inhibitory activity, slight inhibition of selected cytochrome P450s, and low in vitro toxicity. On the basis of this preliminary preclinical profile, inhibitor 22b might be viewed as a promising clinical candidate for the treatment of neurodegenerative diseases.
• WO2006/102958
  申请人：——

  公开号：——

  公开（公告）日：——
• SUBSTITUTED AMINOALKYL- AND AMIDOALKYL-BENZOPYRAN DERIVATIVES
  申请人：Newron Pharmaceuticals S.p.A.

  公开号：EP1863784A1

  公开（公告）日：2007-12-12
• [EN] SUBSTITUTED AMINOALKYL- AND AMIDOALKYL-BENZOPYRAN DERIVATIVES<br/>[FR] DERIVES SUBSTITUES D'AMINOALKYL- ET AMIDOALKYL-BENZOPYRAN
  申请人：NEWRON PHARM SPA

  公开号：WO2006102958A1

  公开（公告）日：2006-10-05

  [EN] This invention is related to novel aminoalkyl- and amidoalkyl- b enzopyran derivatives of the following general formula (I) wherein: the group (a) is a substituent in position 6 or 7 wherein: R is amono- or bi-cyclic (C₆-C₁₀) aryl or a mono- or bi-cyclic (5-10) membered heteroaryl radical, said radicals rings being optionally substituted by one or two substituents selected from (C₁-C₅) straight or branched alkyl, (C₁-C₅) straight or branched alkoxy, hydroxy, halo and trifluoromethyl; m is zero or an integer from 1 to 3; n, p, R₁ and R₂ are as herein indicated and R₃ and R₄ are both hydrogen or taken together represent an oxygen atom, and the pharmaceutically acceptable salts thereof. The compounds that are active as selective and reversible MAO-B inhibitors in vitro
  [FR] L'invention porte sur des dérivés substitués d'aminoalkyl- et amidoalkyl-benzopyran de formule générale (I) dans laquelle: le groupe (II) est un substituant en position 6 ou 7 dans lequel: R est amono- ou aryle (C₆-C₁₀) bicyclique ou un radical hétéroaryle mono ou bicyclique à (5-10) éléments, lesdits cycles des radicaux étant facultativement substitués par un ou deux substituants choisis parmi alkyle (C₁-C₅) droit ou ramifié, alkoxy, hydroxy, halo et trifluorométhyle (C₁-C₅), droits ou ramifiés et m est zéro ou un entier de 1 à 3; dans la formule (I): n, p, R₁ et R₂ sont tels que définis dans la description; et R₃ et R₄ sont tous deux H, ou représentent pris ensemble un atome d'O, ou leurs sels pharmacocompatibles. Lesdits composés agissent en tant qu'inhibiteurs sélectifs et réversibles du MAO-B in vivo et in vitro utiles comme médicaments pour la prévention et le traitement de troubles dégénératifs du SNC.