(R)-4-amino-3,5-dibromophenylalanine methyl ester hydrochloride

• 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: (R)-4-amino-3,5-dibromophenylalanine methyl ester hydrochloride
• 英文别名: methyl (2R)-2-amino-3-(4-amino-3,5-dibromophenyl)propanoate;hydrochloride
• 化学式: C₁₀H₁₂Br₂N₂O₂*ClH
• 分子量: 388.486
• InChiKey: WZGCCAUDJQUHKM-DDWIOCJRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.26
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  78.3
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-4-amino-3,5-dibromophenylalanine methyl ester hydrochloride 在 N-甲基吗啉 、 sodium hydroxide 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 6.75h， 生成 N²-[4-amino-3,5-dibromo-N-(3-phenyl-1-oxopropyl)-D-phenylalanyl]-N⁶-(phenylmethoxycarbonyl)-L-lysine-2-phenethylamide
  参考文献：
  名称：

  Development of Human Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonists. 1. Potent and Selective Small Molecule CGRP Antagonists. 1-[N²-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1- piperidinyl]carbonyl]-d-tyrosyl]-l-lysyl]-4-(4-pyridinyl)piperazine:  The First CGRP Antagonist for Clinical Trials in Acute Migraine

  摘要：

  Although the triptans have greatly improved the acute treatment of migraine headache, there are yet many shortcomings. Therefore, new strategies for the treatment of migraine are needed which offer advantages over current therapy, e.g. triptans. Our novel approach was based on the hypothesis that the release of calcitonin gene-related peptide (CGRP) could play a causative role in migraine headache. Thus we initiated a program aimed at the design and synthesis of small molecule CGRP receptor antagonists. High throughput screening led to the identification of (R)-Tyr-(S)-Lys dipeptide-like compounds that showed weak but unequivocal binding to the human CGRP receptor. Lead optimization afforded highly potent CGRP antagonists, the prototype being compound 19 (BIBN4096). This compound exhibiting a favorable biological profile was selected for initial clinical trials. A proof of concept study indicated that intravenous application of 19 was effective in the treatment of acute migraine headache. This finding strongly supports our initial working hypothesis that CGRP plays an important role in the pathophysiology of migraine.

  DOI：

  10.1021/jm0490641
• 作为产物：
  描述：

  4-氨基-D-苯丙氨酸 在 氯化亚砜 、 氢溴酸 、 溴 、 溶剂黄146 作用下， 反应 1.0h， 生成 (R)-4-amino-3,5-dibromophenylalanine methyl ester hydrochloride
  参考文献：
  名称：

  Development of Human Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonists. 1. Potent and Selective Small Molecule CGRP Antagonists. 1-[N²-[3,5-Dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1- piperidinyl]carbonyl]-d-tyrosyl]-l-lysyl]-4-(4-pyridinyl)piperazine:  The First CGRP Antagonist for Clinical Trials in Acute Migraine

  摘要：

  Although the triptans have greatly improved the acute treatment of migraine headache, there are yet many shortcomings. Therefore, new strategies for the treatment of migraine are needed which offer advantages over current therapy, e.g. triptans. Our novel approach was based on the hypothesis that the release of calcitonin gene-related peptide (CGRP) could play a causative role in migraine headache. Thus we initiated a program aimed at the design and synthesis of small molecule CGRP receptor antagonists. High throughput screening led to the identification of (R)-Tyr-(S)-Lys dipeptide-like compounds that showed weak but unequivocal binding to the human CGRP receptor. Lead optimization afforded highly potent CGRP antagonists, the prototype being compound 19 (BIBN4096). This compound exhibiting a favorable biological profile was selected for initial clinical trials. A proof of concept study indicated that intravenous application of 19 was effective in the treatment of acute migraine headache. This finding strongly supports our initial working hypothesis that CGRP plays an important role in the pathophysiology of migraine.

  DOI：

  10.1021/jm0490641

文献信息

• Modified amino acids, pharmaceuticals containing these compounds and method for their production
  申请人：——

  公开号：US20010036946A1

  公开（公告）日：2001-11-01

  The present invention relates to modified amino acids of general formula 1 wherein A, Z, X, n, m, R, R 2 , R 3 , R 4 and R 11 are defined as in claims 1 to 5 , their tautomers, their diastereomers, their enantiomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, pharmaceutical compositions containing these compounds, the use thereof and processes for preparing them as well as their use for the production and purification of antibodies and as labelled compounds in RIA- and ELISA assays and as diagnostic or analytical aids in neurotransmitter research.

  本发明涉及一般式1的改良氨基酸，其中A、Z、X、n、m、R、R2、R3、R4和R11如权利要求1至5中所定义，它们的互变异构体、对映异构体、混合物及其盐，特别是其与无机或有机酸或碱的生理上可接受的盐，含有这些化合物的药物组合物，其用途以及用于制备它们的过程，以及它们在抗体的生产和纯化中的用途，以及在RIA和ELISA测定中作为标记化合物以及在神经递质研究中作为诊断或分析辅助工具的用途。
• Modified aminoacids, pharmaceuticals containing these compounds and method for their production
  申请人：——

  公开号：US20030069231A1

  公开（公告）日：2003-04-10

  The present invention relates to modified amino acids of general formula 1 wherein A, Z, X, n, m, R, R 2 , R 3 , R 4 and R 11 are defined as in claims 1 to 5, their tautomers, their diastereomers, their enantiomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, pharmaceutical compositions containing these compounds, the use thereof and processes for preparing them as well as their use for the production and purification of antibodies and as labelled compounds in RIA- and ELISA assays and as diagnostic or analytical aids in neurotransmitter research.

  本发明涉及一般式1的改性氨基酸，其中A、Z、X、n、m、R、R2、R3、R4和R11如权利要求1至5所定义，它们的互变异构体、对映异构体、混合物和盐，特别是它们与无机或有机酸或碱的生理上可接受的盐，含有这些化合物的制药组合物，其使用和制备过程，以及它们在抗体的生产和纯化中的使用，作为RIA和ELISA测定中的标记化合物，以及在神经递质研究中作为诊断或分析辅助工具的使用。
• ABGEWANDELTE AMINOSÄUREN, DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL UND VERFAHREN ZU IHRER HERSTELLUNG
  申请人：Boehringer Ingelheim Pharma GmbH & Co.KG

  公开号：EP0927192B1

  公开（公告）日：2004-05-12
• Abgewandelte Aminosäuren, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
  申请人：Boehringer Ingelheim Pharma GmbH & Co.KG

  公开号：EP1440976B1

  公开（公告）日：2008-07-23
• US6344449B1
  申请人：——

  公开号：US6344449B1

  公开（公告）日：2002-02-05