(6S)-3-amino-5,7-dihydrospiro[cyclopenta[c]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one | 1059186-47-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: (6S)-3-amino-5,7-dihydrospiro[cyclopenta[c]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one
• 英文别名: 3-amino-5,7-dihydrospiro[cyclopenta[c]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one；(3S)-3'-aminospiro[1H-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[c]pyridine]-2-one
• CAS: 1059186-47-8
• 化学式: C₁₄H₁₂N₄O
• 分子量: 252.275
• InChiKey: AQBNYNHZFPBXJF-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  80.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (6S)-3-amino-5,7-dihydrospiro[cyclopenta[c]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one 、 [(2S,5S,6R)-2-(3-chlorophenyl)-6-fluoro-4-oxo-1,8-dioxa-3-azaspiro[4.5]dec-3-yl]acetic acid 在 N-甲基吗啉 、 N,N,N',N'-tetramethylchloroformamidinium hexafluorophosphate 、 sodium chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 以25%的产率得到2-[(2S,5S,6R)-2-(3-chlorophenyl)-6-fluoro-4-oxo-1,8-dioxa-3-azaspiro[4.5]dec-3-yl]-N-[(6S)-2'-oxo-1',2',5,7-tetrahydrospiro[cyclopenta[c]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-3-yl]acetamide
  参考文献：
  名称：

  Novel oxazolidinone calcitonin gene-related peptide (CGRP) receptor antagonists for the acute treatment of migraine

  摘要：

  In our efforts to develop CGRP receptor antagonists as backups to MK-3207, 2, we employed a scaffold hopping approach to identify a series of novel oxazolidinone-based compounds. The development of a structurally diverse, potent (20, cAMP + HS IC50 = 0.67 nM), and selective compound (hERG IC50 = 19 mu M) with favorable rodent pharmacokinetics (F = 100%, t(1/2) = 7 h) is described. Key to this development was identification of a 3-substituted spirotetrahydropyran ring that afforded a substantial gain in potency (10 to 35-fold). (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.021
• 作为产物：
  描述：

  7-氮杂-吲哚-2-酮 在 甲醇 、 水 、 palladium diacetate 、 sodium hydride 、 乙二胺 、 三氟乙酸 、 sodium iodide 、 sodium hydroxide 、 lithium hydroxide 、 lithium hexamethyldisilazane 、 2-二环己基磷-2',6'-二异丙氧基-1,1'-联苯 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (6S)-3-amino-5,7-dihydrospiro[cyclopenta[c]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one
  参考文献：
  名称：

  Novel oxazolidinone calcitonin gene-related peptide (CGRP) receptor antagonists for the acute treatment of migraine

  摘要：

  In our efforts to develop CGRP receptor antagonists as backups to MK-3207, 2, we employed a scaffold hopping approach to identify a series of novel oxazolidinone-based compounds. The development of a structurally diverse, potent (20, cAMP + HS IC50 = 0.67 nM), and selective compound (hERG IC50 = 19 mu M) with favorable rodent pharmacokinetics (F = 100%, t(1/2) = 7 h) is described. Key to this development was identification of a 3-substituted spirotetrahydropyran ring that afforded a substantial gain in potency (10 to 35-fold). (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.021

文献信息

• Substituted monocyclic CGRP receptor antagonists
  申请人：Wood Michael R.

  公开号：US20070265225A1

  公开（公告）日：2007-11-15

  Compounds of formula I: (wherein variables A 1 , A 2 , A 3 , A 4 , m, n, J, Q, R 4 , E a , E b , E c , R 6 , R 7 , R e , R f , R PG 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.

  式I的化合物：(其中变量A1、A2、A3、A4、m、n、J、Q、R4、Ea、Eb、Ec、R6、R7、Re、Rf、RPG和Y如本文所述)是CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗涉及CGRP的疾病中使用这些化合物和组合物。
• MONOCYCLIC CGRP RECEPTOR ANTAGONISTS
  申请人：Selnick Harold G.

  公开号：US20110021516A1

  公开（公告）日：2011-01-27

  The present invention is directed to compounds of the formula (I): (wherein variables A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , A 7 , A 8 , G 1 , G 2 , G 3 , G 4 , J, Q, E a , E b , E c , R 6 , R 7 , R PG 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 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.

  本发明涉及式(I)的化合物：（其中变量A1、A2、A3、A4、A5、A6、A7、A8、G1、G2、G3、G4、J、Q、Ea、Eb、Ec、R6、R7、RPG和Y如本文所述），它们是CGRP受体拮抗剂，并且在治疗或预防CGRP参与的疾病，如偏头痛中有用。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] MONOCYCLIC CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RÉCEPTEURS CGRP MONOCYCLIQUES
  申请人：MERCK & CO INC

  公开号：WO2009120652A3

  公开（公告）日：2009-12-30
• US8765759B2
  申请人：——

  公开号：US8765759B2

  公开（公告）日：2014-07-01
• Novel oxazolidinone calcitonin gene-related peptide (CGRP) receptor antagonists for the acute treatment of migraine
  作者：Brendan M. Crowley、Craig A. Stump、Diem N. Nguyen、Craig M. Potteiger、Melody A. McWherter、Daniel V. Paone、Amy G. Quigley、Joseph G. Bruno、Dan Cui、J. Christopher Culberson、Andrew Danziger、Christine Fandozzi、Danny Gauvreau、Amanda L. Kemmerer、Karsten Menzel、Eric L. Moore、Scott D. Mosser、Vijay Reddy、Rebecca B. White、Christopher A. Salvatore、Stefanie A. Kane、Ian M. Bell、Harold G. Selnick、Mark E. Fraley、Christopher S. Burgey

  DOI：10.1016/j.bmcl.2015.07.021

  日期：2015.11

  In our efforts to develop CGRP receptor antagonists as backups to MK-3207, 2, we employed a scaffold hopping approach to identify a series of novel oxazolidinone-based compounds. The development of a structurally diverse, potent (20, cAMP + HS IC50 = 0.67 nM), and selective compound (hERG IC50 = 19 mu M) with favorable rodent pharmacokinetics (F = 100%, t(1/2) = 7 h) is described. Key to this development was identification of a 3-substituted spirotetrahydropyran ring that afforded a substantial gain in potency (10 to 35-fold). (C) 2015 Elsevier Ltd. All rights reserved.