N-(2,6-dichlorobenzoyl)-4-[6-(methylamino)methyl-1-methyl-2,4-dioxo-1,4-dihydroquinazoline-3(2H)-yl]-L-phenylalanine isopropyl ester | 857869-08-0

• 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: N-(2,6-dichlorobenzoyl)-4-[6-(methylamino)methyl-1-methyl-2,4-dioxo-1,4-dihydroquinazoline-3(2H)-yl]-L-phenylalanine isopropyl ester
• 英文别名: Nalpha-(2,6-dichlorobenzoyl)-4-{1-methyl-6-(N-methyl-aminomethyl)-quinazoline-2,4[1H,3H]-dion-3-yl}-L-phenylalanine isopropyl ester；propan-2-yl (2S)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-[1-methyl-6-(methylaminomethyl)-2,4-dioxoquinazolin-3-yl]phenyl]propanoate
• CAS: 857869-08-0
• 化学式: C₃₀H₃₀Cl₂N₄O₅
• 分子量: 597.498
• InChiKey: CDCHZHOTQNNGPH-DEOSSOPVSA-N

物化性质

• 密度：
  1.330±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(2,6-dichlorobenzoyl)-4-[6-(methylamino)methyl-1-methyl-2,4-dioxo-1,4-dihydroquinazoline-3(2H)-yl]-L-phenylalanine isopropyl ester 在 盐酸 作用下， 以 水 、 乙腈 为溶剂， 生成 Nα-(2,6-dichlorobenzoyl)-4-{1-methyl-6-(N-methylamino-methyl)-quinazoline-2,4[1H,3H]-dion-3-yl}-L-phenylalanine isopropyl ester hydrochloride
  参考文献：
  名称：

  WO2006/137450

  摘要：

  公开号：
• 作为产物：
  描述：

  N-(2,6-dichlorobenzoyl)-4-(6-carboxy-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-3(2H)-yl)-L-phenylalanine isopropyl ester 在 氯甲酸乙酯 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 13.5h， 生成 N-(2,6-dichlorobenzoyl)-4-[6-(methylamino)methyl-1-methyl-2,4-dioxo-1,4-dihydroquinazoline-3(2H)-yl]-L-phenylalanine isopropyl ester
  参考文献：
  名称：

  WO2006/137450

  摘要：

  公开号：

文献信息

• 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。
• METHOD FOR PREPARING PHENYLALANINE DERIVATIVES HAVING QUINAZOLINE-DIONE SKELETON AND INTERMEDIATES FOR USE IN THE PREPARATION OF THE DERIVATIVES
  申请人：KATAOKA Noriyasu

  公开号：US20110313154A1

  公开（公告）日：2011-12-22

  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，其表示为以下公式（1），包括以下步骤（a）、（b）和（c）： （a）将以下公式（2）所表示的酰基苯丙氨酸衍生物与羰基引入试剂和特定的蒽酰氨基酸衍生物反应，从而形成相应的羧基不对称脲衍生物； （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，当保护基R3'对应于R3的基团受保护时，使用N-烷基化试剂将连接在喹唑啉二酮环中氮原子上的氢原子取代为N-烷基基团，然后去保护所得产物。通过该方法，可以在工业上获得具有喹唑啉二酮骨架的苯丙氨酸衍生物，且收率高。
• Crystals of hydrochloride salts of a Phenylalanine Derivative, Production Method Thereof and Use Thereof as alpha4 integrin Inhibitors
  申请人：Ajinomoto Co., Inc.

  公开号：EP2402326A1

  公开（公告）日：2012-01-04

  The present invention discloses crystals of phenylalanine derivatives which have a specific structural formula, and particularly crystals which are easy to be used; crystals excellent in preservation stability, humidity resistance or solubility; and crystals which can be manufactured on the industrial scale. The present invention also discloses the production method thereof and use thereof, and particularly the use thereof as an active ingredient of pharmaceutical compositions.

  本发明公开了具有特定结构式的苯丙氨酸衍生物晶体，特别是易于使用的晶体；在保存稳定性、防潮性或溶解性方面具有优异性能的晶体；以及可以工业化生产的晶体。本发明还公开了其生产方法和用途，特别是将其用作药物组合物的活性成分。
• CRYSTAL OF PHENYLALANINE DERIVATIVE, PROCESS FOR PRODUCING THE SAME AND USE THEREOF
  申请人：Ajinomoto Co., Inc.

  公开号：EP1916241B1

  公开（公告）日：2013-06-12