3-ethynyl-2-(2-methoxyethoxymethoxy)biphenyl | 360791-76-0

• 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: 3-ethynyl-2-(2-methoxyethoxymethoxy)biphenyl
• 英文别名: 1-Ethynyl-2-(2-methoxyethoxymethoxy)-3-phenylbenzene
• CAS: 360791-76-0
• 化学式: C₁₈H₁₈O₃
• 分子量: 282.339
• InChiKey: NJVAAIJCHZUAMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-ethynyl-2-(2-methoxyethoxymethoxy)biphenyl 在 10percent Pd/C 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 氢气 、 羟胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 生成 2-(2-Hydroxy-biphenyl-3-yl)-benzofuran-5-carboxamidine
  参考文献：
  名称：

  Development of Serine Protease Inhibitors Displaying a Multicentered Short (<2.3 Å) Hydrogen Bond Binding Mode:  Inhibitors of Urokinase-Type Plasminogen Activator and Factor Xa

  摘要：

  Novel scaffolds that bind to serine proteases through a unique network of short hydrogen bonds to the catalytic Ser195 have been developed. The resulting potent serine protease inhibitors were designed from lead molecule 2-(2-hydroxyphenyl)1H-benzoimidazole-5-carboxamidine, 6b, which is known to display several modes of binding. For instance, 6b can recruit zinc and bind in a manner similar to that reported by bis(5-amidino-2-benzimidazolyl)methane (BABIM) (Nature 1998, 391, 608-612).(1) Alternatively, 6b can bind in the absence of zinc through a multicentered network of short (<2.3 Angstrom) hydrogen bonds. The lead structure was optimized in the zinc-independent binding mode toward a panel of six human serine proteases to yield optimized inhibitors such as 2-(3-bromo-2-hydroxy-5-methylphenyl)-1H-indole-5-carboxamidine, 22a, and 2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine, 22f. Structure-activity relationships determined that, apart from the amidine function, an indole or benzimidazole and an ortho substituted phenol group were also essential components for optimal potency. The affinities (K-i) of 22a and 22f, for example, bearing these groups ranged from 8 to 600 nM toward a panel of six human serine proteases. High-resolution crystal structures revealed that the binding mode of these molecules in several of the enzymes was identical to that of 6b and involved short (<2.3 Angstrom) hydrogen bonds among the inhibitor hydroxyl oxygen, Ser195, and a water molecule trapped in the oxyanion hole. In summation, novel and potent trypsin-like serine protease inhibitors possessing a unique mode of binding have been discovered.

  DOI：

  10.1021/jm0100638
• 作为产物：
  描述：

  2-羟基-[1,1'-联苯]-3-甲醛 在 (1-diazo-2-oxopropyl) dimethyl phosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 3-ethynyl-2-(2-methoxyethoxymethoxy)biphenyl
  参考文献：
  名称：

  Development of Serine Protease Inhibitors Displaying a Multicentered Short (<2.3 Å) Hydrogen Bond Binding Mode:  Inhibitors of Urokinase-Type Plasminogen Activator and Factor Xa

  摘要：

  Novel scaffolds that bind to serine proteases through a unique network of short hydrogen bonds to the catalytic Ser195 have been developed. The resulting potent serine protease inhibitors were designed from lead molecule 2-(2-hydroxyphenyl)1H-benzoimidazole-5-carboxamidine, 6b, which is known to display several modes of binding. For instance, 6b can recruit zinc and bind in a manner similar to that reported by bis(5-amidino-2-benzimidazolyl)methane (BABIM) (Nature 1998, 391, 608-612).(1) Alternatively, 6b can bind in the absence of zinc through a multicentered network of short (<2.3 Angstrom) hydrogen bonds. The lead structure was optimized in the zinc-independent binding mode toward a panel of six human serine proteases to yield optimized inhibitors such as 2-(3-bromo-2-hydroxy-5-methylphenyl)-1H-indole-5-carboxamidine, 22a, and 2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine, 22f. Structure-activity relationships determined that, apart from the amidine function, an indole or benzimidazole and an ortho substituted phenol group were also essential components for optimal potency. The affinities (K-i) of 22a and 22f, for example, bearing these groups ranged from 8 to 600 nM toward a panel of six human serine proteases. High-resolution crystal structures revealed that the binding mode of these molecules in several of the enzymes was identical to that of 6b and involved short (<2.3 Angstrom) hydrogen bonds among the inhibitor hydroxyl oxygen, Ser195, and a water molecule trapped in the oxyanion hole. In summation, novel and potent trypsin-like serine protease inhibitors possessing a unique mode of binding have been discovered.

  DOI：

  10.1021/jm0100638

文献信息

• Exploiting Subsite S1 of Trypsin-Like Serine Proteases for Selectivity:  Potent and Selective Inhibitors of Urokinase-Type Plasminogen Activator
  作者：Richard L. Mackman、Bradley A. Katz、J. Guy Breitenbucher、Hon C. Hui、Erik Verner、Christine Luong、Liang Liu、Paul A. Sprengeler

  DOI：10.1021/jm010244+

  日期：2001.11.1

  2753-2771) has been optimized through minor structural changes on the S1 binding group to afford remarkably selective and potent inhibitors of urokinase-type plasminogen activator (uPA). The trypsin-like serine proteases(1) that comprise drug targets can be broadly categorized into two subfamilies, those with Ser190 and those with Ala190. A single-atom modification, for example, replacement of hydrogen for chlorine

  胰蛋白酶样丝氨酸蛋白酶的非选择性抑制剂2-（2-羟基联苯-3-基）-1H-吲哚-5-甲am（1）（Verner，E .; Katz，BA; Spencer，J .; Allen，D 。; Hataye，J .; Hruzewicz，W .; Hui，HC; Kolesnikov，A .; Li，Y .; Luong，C .; Martelli，A .; Radika。K .; Rai，R .; She，M. ； Shrader，W。； Sprengeler，PA； Trapp，S。； Wang，J； Young，WB； Mackman，RLJ Med.Chem.2001，44，2753-2771）已经通过对S1结合的微小结构变化进行了优化。小组提供尿激酶型纤溶酶原激活剂（uPA）的显着选择性和有效抑制剂。包含药物靶标的胰蛋白酶样丝氨酸蛋白酶（1）可以大致分为两个亚家族，即带有Ser190的