(2-氧代-2,3,5,6-四氢螺[吲哚-3,4-吡喃]-2(1H)-基)乙酸 | 880079-26-5

• 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
• 中文名称: (2-氧代-2,3,5,6-四氢螺[吲哚-3,4-吡喃]-2(1H)-基)乙酸
• 英文名称: (2-oxo-2',3',5',6'-tetrahydrospiro[indole-3,4'-pyran]-2(1H)-yl)acetic acid
• 英文别名: (2-oxo-2',3',5',6'-tetrahydrospiro[indole-3,4'-pyran]-1(2H)-yl)acetic acid；2-(2-Oxo-2',3',5',6'-tetrahydrospiro[indoline-3,4'-pyran]-1-yl)acetic acid；2-(2-oxospiro[indole-3,4'-oxane]-1-yl)acetic acid
• CAS: 880079-26-5
• 化学式: C₁₄H₁₅NO₄
• 分子量: 261.277
• InChiKey: ASMFKWLEUFAWST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S)-5-amino-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one 、 (2-氧代-2,3,5,6-四氢螺[吲哚-3,4-吡喃]-2(1H)-基)乙酸 在 1-羟基苯并三唑 、 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 N,N-二甲基甲酰胺 为溶剂， 生成 CGRP antagonist 1
  参考文献：
  名称：

  The discovery of highly potent CGRP receptor antagonists

  摘要：

  Rational modification of a previously identified spirohydantoin lead structure has identified a series of potent spiroazaoxindole CGRP receptor antagonists. The azaoxindole was found to be a general replacement for the hydantoin that consistently improved in vitro potency. The combination of the indanylspiroazaoxindole and optimized benzimidazolinones led to highly potent antagonists (e.g., 25, CGRP K(i) = 40 pM). The closely related compound 27 demonstrated good oral bioavailability in dog and rhesus. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.106
• 作为产物：
  描述：

  tert-butyl (2-oxo-2',3',5',6'-tetrahydrospiro[indole-3,4'-pyran]-2(1H)-yl)acetate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 (2-氧代-2,3,5,6-四氢螺[吲哚-3,4-吡喃]-2(1H)-基)乙酸
  参考文献：
  名称：

  WO2008/130512

  摘要：

  公开号：

文献信息

• Bicyclic Anilide Spirolactam Cgrp Receptor Antagonists
  申请人：Bell M. Ian

  公开号：US20080096878A1

  公开（公告）日：2008-04-24

  The present invention is directed to compounds of Formula (I): (where variables A 1 , A 2 , B, J, K, m, n, R 4 , R 5a , R 5b and R 5c are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及公式（I）的化合物：（其中变量A1、A2、B、J、K、m、n、R4、R5a、R5b和R5c的定义如本文所述），该化合物可用作CGRP受体拮抗剂，并可用于治疗或预防CGRP参与的疾病，如头痛、偏头痛和集群头痛。本发明还涉及包含这些化合物的制药组合物以及在预防或治疗CGRP参与的这些疾病中使用这些化合物和组合物的用途。
• BICYCLIC ANILIDE HETEROCYCLIC CGRP RECEPTOR ANTAGONISTS
  申请人：Bell Ian M.

  公开号：US20100093759A1

  公开（公告）日：2010-04-15

  Compounds of formula I: I (wherein variables A1, A2, B, m, n, J, R4, G1, G2, G3 and Y are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  公式I的化合物：I（其中变量A1、A2、B、m、n、J、R4、G1、G2、G3和Y如本文所述），它们是CGRP受体拮抗剂，可用于治疗或预防CGRP参与的疾病，如偏头痛。本发明还涉及包含这些化合物的制药组合物以及在预防或治疗CGRP参与的这些疾病中使用这些化合物和组合物。
• Bicyclic anilide heterocyclic CGRP receptor antagonists
  申请人：Merck, Sharp & Dohme Corp.

  公开号：US08173655B2

  公开（公告）日：2012-05-08

  Compounds of formula I: (wherein variables A1, A2, B, m, n, J, R4, G1, G2, G3 and Y are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  化合物I的公式：（其中变量A1，A2，B，m，n，J，R4，G1，G2，G3和Y的描述如下），这些化合物是CGRP受体的拮抗剂，可用于治疗或预防CGRP参与的疾病，如偏头痛。本发明还涉及包含这些化合物的制药组合物以及在预防或治疗CGRP参与的这些疾病中使用这些化合物和组合物。
• [EN] BICYCLIC ANILIDE SPIROLACTAM CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RECEPTEURS DU CGRP DE SPIROLACTAME ANILIDE BICYCLIQUE
  申请人：MERCK & CO INC

  公开号：WO2006031610A3

  公开（公告）日：2006-08-31
• BICYCLIC ANILIDE SPIROLACTAM CGRP RECEPTOR ANTAGONISTS
  申请人：Merck & Co., Inc.

  公开号：EP1797073A2

  公开（公告）日：2007-06-20