p-aminophenylalanine-N-methylamide | 144288-02-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: p-aminophenylalanine-N-methylamide
• 英文别名: (2S)-2-amino-3-(4-aminophenyl)-N-methylpropanamide
• CAS: 144288-02-8
• 化学式: C₁₀H₁₅N₃O
• 分子量: 193.249
• InChiKey: HHROPQCRMSTUQJ-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  81.1
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  p-aminophenylalanine methyl ester 在 甲胺 作用下， 以 乙醇 为溶剂， 以100%的产率得到p-aminophenylalanine-N-methylamide
  参考文献：
  名称：

  P2'-modified hydroxamic acid collagenase inhibitors

  摘要：

  通式I的化合物：##STR1## 其中：R.sup.1、R.sup.2、R.sup.3、R.sup.4、R.sup.5和R.sup.6是变量。这些化合物具有胶原酶抑制活性，并在涉及胶原降解的疾病管理中有用。其用途包括类风湿性关节炎、角膜溃疡、骨质疏松症、牙周炎、牙龈炎和肿瘤侵袭。

  公开号：

  US05300674A1

文献信息

• Hydroxamic acids derivatives, process for their preparation and use thereof
  申请人：BRITISH BIOTECH PHARMACEUTICALS LIMITED

  公开号：EP0498665A1

  公开（公告）日：1992-08-12

  Compounds of general formula I: Wherein : R¹ is hydrogen, C₁ - C₆ alkyl, phenyl, substituted phenyl, phenyl(C₁ - C₆ alkyl), or heterocyclyl; or R¹ is ASOnR⁷ wherein A represents a C₁ - C₆ hydrocarbon chain, optionally substituted with one or more C₁ - C₆ alkyl, phenyl or substituted phenyl groups n = 0,1,2; R⁷ is C₁ - C₆ alkyl, phenyl, substituted phenyl, phenyl (C₁-C₆ alkyl), heterocyclyl, (C₁ - C₆ alkyl)acyl thienyl or phenacyl; R² is hydrogen, C₁ - C₆ alkyl, C₂ - C₆ alkenyl, phenyl (C₁ - C₆alkyl) or cycloalkyl(C₁ - C₆ alkyl); R³ and R⁴ are selected from hydrogen, halogen, cyano amino, amino(C₁ - C₆)alkyl, amino di(C₁ - C₆)alkyl, amino(C₁ - C₆)alkylacyl, aminophenacyl, amino (substituted) phenacyl, amino acid or derivative thereof, hydroxy, oxy(C₁ - C₆)alkyl, oxyacyl, formyl, carboxylic acid, carboxamide, carboxy(C₁ - C₆) alkylamide, carboxyphenylamide, carboxy(C₁ - C₆) alkyl, hydroxy(C₁ - C₆)alkyl, (C₁ - C₆)alkyloxy(C₁ - C₆) alkyl or acyloxy(C₁ - C₆)alkyl, (C₁ - C₆)alkylcarboxylic acid, (C₁-C₆) alkylcarboxy(C₁ - C₆) alkyl, amino (C₁₋₆)alkylacyl carboxylic acid or amino (C₁₋₆)alkylacyl (C₁₋₆) alkylcarboxylate; or R³ is OCH₂COR⁸ R⁴ is hydrogen; wherein R⁸ is hydroxyl, C₁ - C₆ oxyalkyl, C₁ - C₆ oxyalkylphenyl, amino, C₁ - C₆ aminoalkyl, C₁ - C₆ aminodialkyl; C₁ - C₆ aminoalkylphenyl, an amino acid or derivative thereof; or R³ is OCH₂CH₂OR⁹ and R⁴ is hydrogen; wherein R⁹ is C₁ - C₆ alkyl, C₁ - C₆ alkylphenyl, phenyl, substituted phenyl, (C₁ - C₆ alkyl)acyl, or phenacyl; or R³ is OCH₂CN and R⁴ is hydrogen; R⁵ is hydrogen or C₁ - C₆ alkyl, or (C₁ - C₆) alkylphenyl; R⁶ is hydrogen or methyl; or a salt thereof; specifically excluded are compounds wherein: R³ = R⁴ = hydrogen or R³ = R⁴ = hydroxy or R³ = hydrogen and R⁴ = oxybenzyl or R³ = hydrogen and R⁴ = oxy(C₁ - C₆ alkyl); or a salt thereof; have collagenase inhibition activity and are useful in the management of disease involving collagen degradation. Its uses include rheumatoide arthritis, corneal ulceration, osteoporosis, periodontitis, gingivitis and tumour invasion.

  通式 I 的化合物： 其中 ： R¹ 是氢、C₁ - C₆ 烷基、苯基、取代苯基、苯基(C₁ - C₆ 烷基)或杂环基； 或 R¹ 是 ASOnR⁷ 其中 A 代表 C₁ - C₆ 碳氢链，可选择被一个或多个 C₁ - C₆ 烷基、苯基或取代苯基取代 n = 0,1,2; R⁷ 是 C₁ - C₆ 烷基、苯基、取代苯基、苯基 (C₁-C₆ 烷基)、杂环基、(C₁ - C₆ 烷基)酰基噻吩基或苯基； R² 是氢、C₁ - C₆ 烷基、C₂ - C₆ 烯基、苯基 (C₁ - C₆ 烷基) 或环烷基 (C₁ - C₆ 烷基)； R³ 和 R⁴ 选自氢、卤素、氰基氨基、氨基(C₁ - C₆)烷基、氨基二(C₁ - C₆)烷基、氨基(C₁ - C₆)烷酰基、氨基苯酰基、氨基（取代）苯酰基、氨基酸或其衍生物、羟基、氧基（C₁ - C₆）烷基、氧基酰基、甲酰基、羧酸、羧酰胺、羧基（C₁ - C₆）烷基酰胺、(C₁-C₆)烷基、羟基(C₁-C₆)烷基、(C₁-C₆)烷氧基(C₁-C₆)烷基或酰氧基(C₁-C₆)烷基、(C₁-C₆)烷基羧酸、(C₁-C₆)烷基羧基(C₁ - C₆)烷基、氨基(C₁₋₆)烷基酰基羧酸或氨基(C₁₋₆)烷基酰基(C₁₋₆)烷基羧酸； 或 R³ 是 OCH₂COR⁸ R⁴ 是氢； 其中 R⁸ 是羟基、C₁ - C₆ 氧烷基、C₁ - C₆ 氧烷基苯基、氨基、C₁ - C₆ 氨基烷基、C₁ - C₆ 氨基二烷基、C₁ - C₆ 氨基烷基苯基、氨基酸或其衍生物； 或 R³ 是 OCH₂CH₂OR⁹，R⁴ 是氢； 其中 R𠞙 是 C₁ - C₆ 烷基、C₁ - C₆ 烷基苯基、苯基、取代苯基、(C₁ - C₆ 烷基)酰基或苯酰基； 或 R³ 是 OCH₂CN，R⁴ 是氢； R⁵ 是氢或 C₁ - C₆ 烷基，或 (C₁ - C₆) 烷基苯基； R⁶ 是氢或甲基； 或其盐； 特别排除以下化合物 R³ = R⁴ = 氢 或 R³ = R⁴ = 羟基 或 R³ = 氢且 R⁴ = 氧苄 或 R³ = 氢且 R⁴ = 氧(C₁ - C₆ 烷基)； 或其盐； 具有胶原酶抑制活性，可用于治疗涉及胶原降解的疾病。其用途包括风湿性关节炎、角膜溃疡、骨质疏松症、牙周炎、牙龈炎和肿瘤侵袭。
• US5300674A
  申请人：——

  公开号：US5300674A

  公开（公告）日：1994-04-05
• US5412145A
  申请人：——

  公开号：US5412145A

  公开（公告）日：1995-05-02
• [EN] HYDROXAMIC ACID DERIVATIVES, PROCESS FOR THEIR PREPARATION AND USE THEREOF
  申请人：——

  公开号：WO1992013831A1

  公开（公告）日：1992-08-20

  [FR] On décrit des composés de formule générale (I) dans laquelle: R1 est hydrogène, C1-C6 alkyle, phényle, phényle substitué, phényl(C1-C6 alkyle), ou hétérocyclyle; ou bien R1 est ASOnR7, où A représente une chaîne hydrocarbure C1-C6, éventuellement substituée par un ou plusieurs groupes alkyle C1-C6, phényle ou phényle substitué; n = 0, 1, 2; R7 est alkyle C1-C6, phényle, phényle substitué, phényl(C1-C6 alkyle), hétérocyclyle, (C1-C6 alkyl)acyle thiényle ou phénacyle; R2 est hydrogène, C1-C6 alkyle, C1-C6 alcényle, phényl(C1-C6 alkyle) ou cycloalkyl(C1-C6 alkyle); R3 et R4 sont choisis parmi hydrogène, halogène, cyano amino, amino(C1-C6)alkyle, amino di(C1-C6)alkyle, amino(C1-C6)alkylacyle, aminophénacyle, amino (substitué) phénacyle, acide aminé ou un de leurs dérivés, hydroxy, oxy(C1-C6)alkyle, oxyacyle, formyle, acide carboxylique, carboxamide, carboxy(C1-C6), alcylamide, carboxyphénylamide, carboxy(C1-C6)alkyle, hydroxy(C1-C6)alcyle, (C1-C6)alcyloxy(C1-C6)alkyle ou acyloxy(C1-C6)alkyle, (C1-C6)acide alkylcarboxylique, (C1-C6)alkylcarboxy(C1-C6)alkyle, amino (C1-C6)alkylacyle acide carboxylique ou amino(C1-C6)alkylacyle (C1-C6)alkylcarboxylate; ou bien R3 est OCH2COR8 et R4 est hydrogène; où R8 est hydroxyle, (C1-C6)oxyalkyle, (C1-C6)oxyalkylphényle, amino, (C1-C6)aminoalkyle, (C1-C6)aminodialkyle, (C1-C6)aminoalkylphényle, un acide aminé ou un de ses dérivés; ou bien R3 est OCH2CH2OR9 et R4 est hydrogène; où R9 est (C1-C6)alkyle, (C1-C6)alkylphényle, phényle, phényle substitué, (C1-C6 alkyle)acyle, ou phénacyle; ou bien R3 est OCH2CN et R4 est hydrogène; R5 est hydrogène ou (C1-C6)alkyle, ou (C1-C6)alkylphényle; R6 est hydrogène ou méthyle; ou l'un de leurs sels; sont spécifiquement exclus les composés dans lesquels: R3 = R4 = hydrogène, ou R3 = R4 = hydroxy ou R3 = hydrogène et R4 = oxybenzyle, ou R3 = hydrogène et R4 = oxy(C1-C6)alkyle; ou un de leurs sels. Ces composés présentent une activité inhibitrice de collagénase et sont utiles dans la gestion des maladies liés à la dégradation du collagène. Leurs
  [EN] Compounds of general formula (I): wherein R?1 is hydrogen, C1?-C6? alkyl, phenyl, substituted phenyl, phenyl(C1?-C6? alkyl), or heterocyclyl; or R?1 is ASOn?R?7 wherein A represents a C1?-C6? hydrocarbon chain, optionally substituted with one or more C1?-C6? alkyl, phenyl or substituted phenyl groups n = 0, 1, 2; R?7 is C1?-C6? alkyl, phenyl, substituted phenyl, phenyl(C1?-C6? alkyl), heterocyclyl, (C1?-C6? alkyl)acyl thienyl or phenacyl; R?2 is hydrogen, C1?-C6? alkyl, C2?-C6? alkenyl, phenyl (C1?-C6? alkyl) or cycloalkyl(C1?-C6? alkyl); R?3 and R?4 are selected from hydrogen, halogen, cyano amino, amino(C1?-C6?)alkyl, amino di (C1?-C6?)alkyl, amino(C1?-C6?)alkylacyl, aminophenacyl, amino (substituted phenacyl, amino acid or derivative thereof, hydroxy, oxy(C1?-C6?)alkyl, oxyacyl, formyl, carboxylic acid, carboxamide, carboxy (C1?-C6?) alkylamide, carboxyphenylamide, carboxy(C1?-C6?) alkyl, hydroxy(C1?-C6?)alkyl, (C1?-C6?)alkyloxy(C1?-C6?) alkyl or acyloxy(C1?-C6?)alkyl, (C1?-C6?)alkylcarboxylic acid, (C1?-C6?) alkylcarboxy (C1?-C6?) alkyl, amino (C1-6?)alkylacyl carboxylic acid or amino (C1-6?)alkylacyl (C1-6?) alkylcarboxylate; or R?3 is OCH2?COR?8 R?4 is hydrogen; wherein R?8 is hydroxyl, C1?-C6? oxyalkyl, C1?-C6? oxyalkylphenyl, amino, C1?-C6? aminoalkyl, C1?-C6? aminodialkyl, C1?-C6? aminoalkylphenyl, an amino acid or derivative thereof; or R?3 is OCH2?CH2?OR?9 and R?4 is hydrogen; wherein R?6 is C1?-C6? alkyl, C1?-C6? alkylphenyl, phenyl, substituted phenyl, (C1?-C6? alkyl)acyl, or phenacyl; or R?3 is OCH2?CN and R?4 is hydrogen; R?5 is hydrogen or C1?-C6? alkyl, or (C1?-C6?) alkylphenyl; R?6 is hydrogen or methyl; or a salt thereof; specifically excluded are compounds wherein: R?3 = R?4 = hydrogen or R?3 = R?4 = hydroxy or R?3 = hydrogen and R?4 = oxybenzyl or R?3 = hydrogen and R?4 = oxy(C1?-C6? alkyl); or a salt thereof; have collagenase inhibition activity and are useful in the management of disease involving collagen degradation. Its uses include rheumatoid arthritis, corneal ulceration, osteoporosis, periodontitis, gingivitis and tumour invasion.