{7-[(3-chlorobenzyl)oxy]-2-oxo-2H-chromen-4-yl}acetonitrile | 911290-31-8

• 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: {7-[(3-chlorobenzyl)oxy]-2-oxo-2H-chromen-4-yl}acetonitrile
• 英文别名: 4-cyanomethyl-7-(3-chlorobenzyloxy)-2H-chromen-2-one；2-[7-[(3-chlorophenyl)methoxy]-2-oxochromen-4-yl]acetonitrile
• CAS: 911290-31-8
• 化学式: C₁₈H₁₂ClNO₃
• 分子量: 325.751
• InChiKey: GJOXPEUFUOYRAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  {7-[(3-chlorobenzyl)oxy]-2-oxo-2H-chromen-4-yl}acetonitrile 在 sodium tetrahydroborate 、 cobalt(II) chloride hexahydrate 、 盐酸 、 氨 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 生成 4-(2-aminoethyl)-7-(3-chlorobenzyloxy)-2H-chromen-2-one
  参考文献：
  名称：

  Discovery of a Novel Class of Potent Coumarin Monoamine Oxidase B Inhibitors: Development and Biopharmacological Profiling of 7-[(3-Chlorobenzyl)oxy]-4-[(methylamino)methyl]-2H-chromen-2-one Methanesulfonate (NW-1772) as a Highly Potent, Selective, Reversible, and Orally Active Monoamine Oxidase B Inhibitor

  摘要：

  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.

  DOI：

  10.1021/jm9010127
• 作为产物：
  描述：

  ethyl (7-hydroxy-2-oxo-2H-chromen-4-yl)acetate 在 吡啶 、 氨 、 三苯基膦 、 三氟乙酸酐 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 反应 78.0h， 生成 {7-[(3-chlorobenzyl)oxy]-2-oxo-2H-chromen-4-yl}acetonitrile
  参考文献：
  名称：

  WO2006/102958

  摘要：

  公开号：

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。
• 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.
• 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：——