N-[(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-({(2S)-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'-dihydro-1H-spiro[piperidine-4,4'-pyrido[2,3-d][1,3]oxazine]-1-carboxamide | 2097085-63-5

• 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-[(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-({(2S)-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'-dihydro-1H-spiro[piperidine-4,4'-pyrido[2,3-d][1,3]oxazine]-1-carboxamide
• 英文别名: Htl-0022562；N-[(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-[[(2S)-1-oxo-3-piperidin-4-yl-1-(4-pyridin-4-ylpiperazin-1-yl)propan-2-yl]amino]propan-2-yl]-2-oxospiro[1H-pyrido[2,3-d][1,3]oxazine-4,4'-piperidine]-1'-carboxamide
• CAS: 2097085-63-5
• 化学式: C₄₀H₄₉N₁₁O₅
• 分子量: 763.9
• InChiKey: LIPVCPUZWNTQHV-SAIUNTKASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  56
• 可旋转键数：
  9
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  190
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (S)-1-boc-4-(2-cbz-氨基-2-甲氧基羰基乙基)哌啶 在 钯 lithium hydroxide 、 sodium hydrogen sulfate 、 N,N-二异丙基乙胺 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 氢气 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 、 乙醇 、 二氯甲烷 为溶剂， 生成 N-[(2R)-3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-({(2S)-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'-dihydro-1H-spiro[piperidine-4,4'-pyrido[2,3-d][1,3]oxazine]-1-carboxamide
  参考文献：
  名称：

  [EN] CGRP RECEPTOR ANTAGONISTS
  [FR] ANTAGONISTES DU RÉCEPTEUR CGRP

  摘要：

  本公开涉及公式（I）中的新化合物，其中R1、R2、R3和R4如本文所定义，并且它们在治疗、预防、改善、控制或减少与CGRP受体功能相关的脑血管或血管疾病中的用途。

  公开号：

  WO2017072721A1

文献信息

• CGRP receptor antagonists
  申请人：Heptares Therapeutics Limited

  公开号：US10300056B2

  公开（公告）日：2019-05-28

  The disclosures herein relate to novel compounds of formula wherein R1, R2, R3 and R4 are as defined herein, and their use in treating, preventing, ameliorating, controlling or reducing cerebrovascular or vascular disorders associated with CGRP receptor function.

  本文所披露的内容涉及新型式化合物 其中 R1、R2、R3 和 R4 如本文所定义，以及它们在治疗、预防、改善、控制或减少与 CGRP 受体功能相关的脑血管或血管紊乱中的用途。
• Structure-Based Drug Discovery of <i>N</i>-((<i>R</i>)-3-(7-Methyl-1<i>H</i>-indazol-5-yl)-1-oxo-1-(((<i>S</i>)-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-<i>d</i>][1,3]oxazine]-1-carboxamide (HTL22562): A Calcitonin Gene-Related Peptide Receptor Antagonist for Acute Treatment of Migraine
  作者：Sarah J. Bucknell、Mark A. Ator、Alastair J. H. Brown、Jason Brown、Andrew D. Cansfield、Julie E. Cansfield、John A. Christopher、Miles Congreve、Gabriella Cseke、Francesca Deflorian、Christopher R. Jones、Jonathan S. Mason、M. Alistair O’Brien、Gregory R. Ott、Mark Pickworth、Stacey M. Southall

  DOI：10.1021/acs.jmedchem.0c01003

  日期：2020.7.23

  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.
• CGRP RECEPTOR ANTAGONISTS
  申请人：Heptares Therapeutics Limited

  公开号：EP3368525B1

  公开（公告）日：2019-03-13
• CGRP Receptor Antagonists
  申请人：Heptares Therapeutics Limited

  公开号：US20170121348A1

  公开（公告）日：2017-05-04

  The disclosures herein relate to novel compounds of formula wherein R 1 , R 2 , R 3 and R 4 are as defined herein, and their use in treating, preventing, ameliorating, controlling or reducing cerebrovascular or vascular disorders associated with CGRP receptor function.
• PRODRUGS OF CGRP ANTAGONISTS
  申请人：Biohaven Pharmaceutical Holding Company Ltd.

  公开号：US20210395223A1

  公开（公告）日：2021-12-23

  Disclosed are prodrugs of CGRP antagonists, methods of treating CGRP related disorders, e.g., migraine, by administering to a patient in need thereof the prodrugs, pharmaceutical compositions comprising prodrugs and kits including the pharmaceutical compositions and instructions for use.