methyl 3-(4-aminophenyl)-2-[(2,6-dichlorobenzoyl)amino]propionate | 554419-04-4

• 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: methyl 3-(4-aminophenyl)-2-[(2,6-dichlorobenzoyl)amino]propionate
• 英文别名: methyl 4-amino-N-(2,6-dichlorobenzoyl)-L-phenylalaninate；N-(2,6-dichlorobenzoyl)-4-amino-L-phenylalanine methylester；(N-2,6-dichlorobenzoyl)-L-4-aminophenylalanine methyl ester；Nα-(2,6-dichlorobenzoyl)-4-amino-L-phenylalanine methyl ester；Methyl (S)-3-(4-aminophenyl)-2-(2,6-dichlorobenzamido)propanoate；methyl (2S)-3-(4-aminophenyl)-2-[(2,6-dichlorobenzoyl)amino]propanoate
• CAS: 554419-04-4
• 化学式: C₁₇H₁₆Cl₂N₂O₃
• 分子量: 367.232
• InChiKey: QRBSHIWRBQCSBT-AWEZNQCLSA-N

物化性质

• 沸点：
  541.4±50.0 °C(Predicted)
• 密度：
  1.359±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  81.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-aminophenyl)-2-[(2,6-dichlorobenzoyl)amino]propionate 、 5-甲氧基-2-硝基苯甲酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  Novel phenylalanine derivatives

  摘要：

  特定的苯丙氨酸衍生物及其类似物具有对α4整合素的拮抗活性。它们被用作治疗涉及α4整合素的各种疾病的药物。

  公开号：

  US20050222141A1
• 作为产物：
  描述：

  (S)-methyl 2-(2,6-dichlorobenzamido)-3-(4-nitrophenyl)propanoate 生成 methyl 3-(4-aminophenyl)-2-[(2,6-dichlorobenzoyl)amino]propionate
  参考文献：
  名称：

  NEW PHENYLALANINE DERIVATIVES

  摘要：

  指定的苯丙氨酸衍生物及其类似物具有对α4整合素的拮抗作用。它们被用作治疗涉及α4整合素的各种疾病的治疗剂。

  公开号：

  US20120253041A1
• 作为试剂：
  描述：

  Nα-(2,6-dichlorobenzoyl)-4-{2-ethoxycarbonyl-amino-5-(N-formyl-N-methylaminomethyl)benzoylamino}-L-phenylalanine isopropyl ester 、 N,N-二甲基甲酰胺 、 potassium carbonate 、 对甲苯磺酸甲酯 在 水 、 intended compound 、 methyl 3-(4-aminophenyl)-2-[(2,6-dichlorobenzoyl)amino]propionate 、 N,N-二甲基甲酰胺 、 甲醇 、 title compound 作用下， 以 溶剂黄146 、 异丙醇 为溶剂， 反应 53.0h， 生成 Nα-(2,6-dichlorobenzoyl)-4-{1-methyl-6-(N-formyl-N-methylaminomethyl)quinazoline-2,4[1H,3H]-dion-3-yl}-L-phenylalanine isopropyl ester
  参考文献：
  名称：

  Method for preparing phenylalanine derivatives having quinazoline-dione skeleton and intermediates for use in the preparation of derivatives

  摘要：

  本发明涉及一种制备具有以下式（1）所表示的喹唑啉二酮环的苯丙氨酸化合物或其药学上可接受的盐的方法：其中R1-R4在此定义。该方法涉及将指定的酰基苯丙氨酸化合物与羰基引入试剂和指定的蒽酰氨酸化合物反应，形成羧基不对称脲化合物，该化合物在羧基活化剂的存在下转化为喹唑啉二酮化合物。

  公开号：

  US08058432B2

文献信息

• Phenylalanine derivatives
  申请人：Celltech Therapeutics Limited

  公开号：US06329372B1

  公开（公告）日：2001-12-11

  Phenylalanine derivatives of formula (1) are described: wherein R is a carboxylic acid or a derivative thereof; L1 is a linker atom or group; Het is an optionally substituted heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of alpha4 integrins to their ligands and are of use in the prophylaxis and treatment of immune or inflammatory disorders.

  描述了式（1）的苯丙氨酸衍生物：其中R为羧酸或其衍生物；L1为连接原子或基团；Het为可选择取代的杂芳基团；以及它们的盐、溶剂合物、水合物和N-氧化物。这些化合物能够抑制α4整合素与其配体的结合，并可用于预防和治疗免疫或炎症性疾病。
• METHODS FOR PRODUCING PHENYLALANINE DERIVATIVES HAVING A QUINAZOLINEDIONE SKELETON AND INTERMEDIATES FOR PRODUCTION THEREOF
  申请人：Kataoka Noriyasu

  公开号：US20100204505A1

  公开（公告）日：2010-08-12

  The present invention provides a method for producing a phenylalanine derivative(s) having a quinazolinedione ring of formula (5), including steps comprising of reacting an acylphenylalanine derivative(s) of formula (1) with a carbonyl group-introducing reagent(s) and a derivative(s) of anthranilic acid to form an asymmetric urea intermediate(s); making the asymmetric urea intermediate(s) into a quinazolinedione compound(s) of formula (4) in the presence of a base(s); and N-alkylating quinazolinedione ring amide of the obtained quinazolinedione compounds with N-alkylation agents. This production method is an industrially applicable method for producing phenylalanine derivatives having a quinazolinedione skeleton, which are compounds highly useful as drugs having α 4 integrin inhibiting activity. In the formulae (1) and (5), R1 represents a phenyl group having a substituent(s) and the like, R2 represents an alkyl group and the like, R3 represents a dialkylamino group and the like, and R4 represents an alkyl group and the like.

  本发明提供了一种制备具有公式（5）的喹唑啉二酮环的苯丙氨酸衍生物的方法，包括以下步骤：将公式（1）的酰基苯丙氨酸衍生物与羰基引入试剂和蒽酸衍生物反应，形成不对称脲中间体；在碱的存在下将不对称脲中间体制成公式（4）的喹唑啉二酮化合物；并用N-烷基化试剂对所得喹唑啉二酮化合物的喹唑啉二酮环酰胺进行N-烷基化。该制备方法是一种工业上适用的制备苯丙氨酸衍生物的方法，这些衍生物具有α4整合素抑制活性，是非常有用的药物化合物。在公式（1）和（5）中，R1代表具有取代基等的苯基，R2代表烷基等，R3代表二烷基胺基等，R4代表烷基等。
• NEW PHENYLALANINE DERIVATIVES
  申请人：MAKINO Shingo

  公开号：US20120253041A1

  公开（公告）日：2012-10-04

  Specified phenylalanine derivatives and analogues thereof have an antagonistic activity to α4 integrin. They are used as therapeutic agents for various diseases concerning α4 integrin.

  指定的苯丙氨酸衍生物及其类似物具有对α4整合素的拮抗作用。它们被用作治疗涉及α4整合素的各种疾病的治疗剂。
• PHENYLALANINE DERIVATIVES
  申请人：Arnould Jean-Claude

  公开号：US20080045521A1

  公开（公告）日：2008-02-21

  The present invention relates to compounds that inhibit of a5b1 function, processes for their preparation, pharmaceutical compositions containing them as the active ingredient, to their use as medicaments and to their use in the manufacture of medicaments for use in the treatment in warm-blooded animals such as humans of diseases that have a significant angiogenesis or vascular component such as for treatment of solid tumours. The present invention also relates to a5b1 antagonists that also exhibit appropriate selectivity profile(s) against other integrins.

  本发明涉及抑制a5b1功能的化合物，其制备过程，含有其作为活性成分的制药组合物，以及它们作为药物在温血动物（如人类）中治疗具有明显血管生成或血管成分的疾病，例如固体肿瘤的制药用途。本发明还涉及a5b1拮抗剂，其还表现出对其他整合素的适当选择性特征。
• METHOD FOR PREPARING PHENYLALANINE DERIVATIVES HAVING QUINAZOLINE-DIONE SKELETON AND INTERMEDIATES FOR USE IN THE PREPARATION OF DERIVATIVES
  申请人：KATAOKA Noriyasu

  公开号：US20090318688A1

  公开（公告）日：2009-12-24

  A method for preparing a phenylalanine derivative having a quinazoline-dione ring represented by the following formula (1) or a pharmaceutically acceptable salt thereof, comprising the following steps (a), (b) and (c): (a) reacting an acyl phenylalanine derivative represented by the following formula (2): with a carbonyl group-introducing reagent and a specific anthranilic acid derivative to thus form the corresponding carboxy-asymmetric urea derivative; (b) converting the carboxy-asymmetric urea derivative into the corresponding quinazoline-dione derivative in the presence of a carboxyl group-activating agent: (c) if desired, substituting an N-alkyl group for the hydrogen atom bonded to the nitrogen atom present in the quinazoline-dione ring of the quinazoline-dione derivative using an N-alkylation agent and then deprotecting the resulting product, when the substituent R3′ which is a group corresponding to R3 is protected. According to this method, there can be obtained a phenylalanine derivative having a quinazoline-dione skeleton in a industrially favorably high yield.

  一种制备具有喹唑啉二酮环的苯丙氨酸衍生物或其药学上可接受的盐的方法，其由以下步骤(a)、(b)和(c)组成：(a)用羰基基团引入试剂和特定的蒽酸衍生物反应，以形成相应的羧基-不对称脲衍生物，所述脲衍生物由以下式(2)所表示的酰基苯丙氨酸衍生物反应而成：(b)在羧基活化剂的存在下，将羧基-不对称脲衍生物转化为相应的喹唑啉二酮衍生物；(c)如果需要，在R3'是被保护的基团对应的R3时，使用N-烷基化试剂将取代喹唑啉二酮环中氮原子上的氢原子的N-烷基基团替换，并去保护所得产物。根据该方法，可以得到一个工业上有利的高产率的具有喹唑啉二酮骨架的苯丙氨酸衍生物。