Nα-(2,6-dichlorobenzoyl)-4-nitro-L-phenylalanine | 401906-14-7

• 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: Nα-(2,6-dichlorobenzoyl)-4-nitro-L-phenylalanine
• 英文别名: 4-nitro-N-(2,6-dichlorobenzoyl)-L-phenylalanine；N-(2,6-Dichlorobenzoyl)-4-nitro-L-phenylalanine；(2S)-2-[(2,6-dichlorobenzoyl)amino]-3-(4-nitrophenyl)propanoic acid
• CAS: 401906-14-7
• 化学式: C₁₆H₁₂Cl₂N₂O₅
• 分子量: 383.188
• InChiKey: PPPNTBPVQUEWKE-ZDUSSCGKSA-N

物化性质

• 沸点：
  593.0±50.0 °C(Predicted)
• 密度：
  1.507±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Nα-(2,6-dichlorobenzoyl)-4-nitro-L-phenylalanine 在 palladium diacetate 硫酸 、 氢气 、 potassium carbonate 、 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 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 151.0h， 生成 N-(2,6-dichlorobenzoyl)-4-(6-carboxy-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-3(2H)-yl)-L-phenylalanine isopropyl ester
  参考文献：
  名称：

  WO2006/137450

  摘要：

  公开号：
• 作为产物：
  描述：

  2-(3-{4-[2-(2,6-dichlorobenzoylamino)-2-methoxycarbonylethyl]phenyl}ureido)-5-dimethylaminobenzoic acid methyl ester 以97的产率得到Nα-(2,6-dichlorobenzoyl)-4-nitro-L-phenylalanine
  参考文献：
  名称：

  METHODS FOR PRODUCING PHENYLALANINE DERIVATIVES HAVING A QUINAZOLINEDIONE SKELETON AND INTERMEDIATES FOR PRODUCTION THEREOF

  摘要：

  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。

  公开号：

  US20100204505A1

文献信息

• Novel phenylalanine derivatives
  申请人：Sagi Kazuyuki

  公开号：US20050222141A1

  公开（公告）日：2005-10-06

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

  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。
• 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。
• Methods for producing phenylalanine derivatives having a quinazolinedione skeleton and intermediates for production thereof
  申请人：Kataoka Noriyasu

  公开号：US20060009476A1

  公开（公告）日：2006-01-12

  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.

  本发明提供了一种生产具有公式（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醌酸衍生物反应，形成不对称脲中间体；在碱的存在下，将不对称脲中间体制备成公式（4）的喹唑啉二酮化合物；将所得的喹唑啉二酮化合物的喹唑啉二酮环酰胺进行N-烷基化反应。该生产方法是一种工业上可应用的方法，用于生产具有喹唑啉骨架的苯丙氨酸衍生物，这些化合物作为具有α4整合素抑制活性的药物非常有用。在公式（1）和（5）中，R1表示具有取代基的苯基或类似物，R2表示烷基或类似物，R3表示二烷基氨基基团或类似物，R4表示烷基或类似物。
• 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。
• NOVEL PHENYLALANINE DERIVATIVES
  申请人：SAGI Kazuyuki

  公开号：US20080108634A1

  公开（公告）日：2008-05-08

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

  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。它们被用作治疗与α4整合素相关的各种疾病的治疗剂。