3,5-dibromo-N-{[4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidin-1-yl]carbonyl}-D-tyrosine | 862805-23-0

• 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: 3,5-dibromo-N-{[4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidin-1-yl]carbonyl}-D-tyrosine
• 英文别名: 3,5-Dibromo-n-[[4-(1,4-dihydro-2-oxo-3(2h)-quinazolinyl)-1-piperidinyl]carbonyl]-d-tyrosine；(2R)-3-(3,5-dibromo-4-hydroxyphenyl)-2-[[4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carbonyl]amino]propanoic acid
• CAS: 862805-23-0
• 化学式: C₂₃H₂₄Br₂N₄O₅
• 分子量: 596.275
• InChiKey: GAXQZRYPNGMJLQ-LJQANCHMSA-N

物化性质

• 沸点：
  829.8±65.0 °C(Predicted)
• 密度：
  1.700±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  122
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,5-dibromo-N-{[4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidin-1-yl]carbonyl}-D-tyrosine 、 [(5S)-5-amino-6-oxo-6-[4-(4-pyridinyl)-1-piperazinyl]hexyl]-carbamic acid 1,1-dimethylethyl ester monotetrafluorborate 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 14.0h， 以83%的产率得到[R-(R*,S*)]-[5-[[3-(3,5-dibromo-4-hydroxyphenyl)-2-[[[4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-1-piperidinyl]carbonyl]amino]-1-oxopropyl]amino]-6-oxo-6-[4-(4-pyridinyl)-1-piperazinyl]hexyl]-carbamoyl acid-1,1-dimethylethylester
  参考文献：
  名称：

  Process for preparing 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

  摘要：

  本申请涉及一种制备CGRP拮抗剂1-[N2-[3,5-二溴-N-[[4-(3,4-二氢-2(1H)-氧喹唑啉-3-基)-1-哌啶基]羰基]-D-酪氨酰]-L-赖氨酰]-4-(4-吡啶基)-哌嗪的方法，通过该方法可以大量、高产率且高纯度地制备该化合物。

  公开号：

  US20050192230A1
• 作为产物：
  描述：

  3,5-二溴吲哚-d-酪氨酸甲酯 在 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 3,5-dibromo-N-{[4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidin-1-yl]carbonyl}-D-tyrosine
  参考文献：
  名称：

  Structure-Based Drug Discovery of N-((R)-3-(7-Methyl-1H-indazol-5-yl)-1-oxo-1-(((S)-1-oxo-3-(piperidin-4-yl)-1-(4-(pyridin-4-yl)piperazin-1-yl)propan-2-yl)amino)propan-2-yl)-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxamide (HTL22562): A Calcitonin Gene-Related Peptide Receptor Antagonist for Acute Treatment of Migraine

  摘要：

  Structure-based drug design enabled the discovery of 8, HTL22562, a calcitonin gene-related peptide (CGRP) receptor antagonist. The structure of 8 complexed with the CGRP receptor was determined at a 1.6 angstrom resolution. Compound 8 is a highly potent, selective, metabolically stable, and soluble compound suitable for a range of administration routes that have the potential to provide rapid systemic exposures with resultant high levels of receptor coverage (e.g., subcutaneous). The low lipophilicity coupled with a low anticipated clinically efficacious plasma exposure for migraine also suggests a reduced potential for hepatotoxicity. These properties have led to 8 being selected as a clinical candidate for acute treatment of migraine.

  DOI：

  10.1021/acs.jmedchem.0c01003

文献信息

• Carboxylic acids and the esters thereof, pharmaceutical compositions thereto and processes for the preparation thereof
  申请人：Boehringer Ingelheim International GmbH

  公开号：US20040192729A1

  公开（公告）日：2004-09-30

  The present invention relates to carboxylic acids and esters of general formula 1 wherein Ar, R, R 1 , X 1 , X 3 , X 4 , Y and Y 1 are defined as in claim 1, the tautomers, the diastereomers, the 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 the preparation thereof, as well as the use thereof 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.

  本发明涉及通式1的羧酸和酯，其中Ar、R、R1、X1、X3、X4、Y和Y1如权利要求1中所定义，其互变异构体、顺反异构体、对映体、其混合物及其盐，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，其用途和制备方法，以及其用于抗体的生产和纯化以及在放射免疫测定和酶联免疫吸附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。
• [DE] VERFAHREN ZUR HERSTELLUNG VON 1-[N<2>-[3,5-DIBROM-N-[[4-(3,4-DIHYDRO-2(1H)-OXOCHINAZOLIN-3-YL)-1-PIPERIDINYL]CARBONYL]-D-TYROSYL]-L-IYSYL]-4-(4-PYRIDINYL)-PIPERAZIN<br/>[EN] METHOD FOR THE PRODUCTION OF 1-[N<2>-[3,5-DIBROMO-N-[[4-(3,4-DIHYDRO-2(1H)-OXOQUINAZOLINE-3-YL)-1-PIPERIDINYL]CARBONYL]-D-TYROSYL]-L-LYSYL]-4-(4-PYRIDINYL)-PIPERAZINE<br/>[FR] PROCEDE DE FABRICATION DE 1-[N<2>-[3,5-DIBROMO-N-[[4-(3,4-DIHYDRO-2(1H)-OXOQUINAZOLINE-3-YL)-1-PIPERIDINYL]CARBONYL]-D-TYROSYL]-L-IYSYL]-4-(4-PYRIDINYL)-PIPERAZINE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2005077931A3

  公开（公告）日：2005-12-22
• Serendipitous oxidation product of BIBN4096BS: A potent CGRP receptor antagonist
  作者：Bireshwar Dasgupta、Edward Kozlowski、Daniel R. Schroeder、John R. Torrente、Cen Xu、Sokhom Pin、Charlie M. Conway、Gene M. Dubowchik、John E. Macor、Vivekananda M. Vrudhula

  DOI：10.1016/j.bmcl.2014.04.033

  日期：2014.6

  An oxidation product (5) formed during the synthesis of BIBN-4096BS (1) was found to be a potent CGRP antagonist (IC50 = 0.11 nM). While 5 was found to be ten-fold less potent than 1, another analog 8 with lower molecular weight containing the oxidized fragment demonstrated twenty-fold higher activity than its parent 7. Alternative conditions which preclude the formation of the oxidation product are described. The activities of 1, 5, 7 and 8 in functional cAMP assay are also discussed. (C) 2014 Elsevier Ltd. All rights reserved.
• Bioorg. Med. Chem. Lett. 2014, 24, 2744-2748
  作者：

  DOI：——

  日期：——
• CGRP RECEPTOR ANTAGONISTS
  申请人：Heptares Therapeutics Limited

  公开号：EP3368525B1

  公开（公告）日：2019-03-13