3-(4-benzyloxy-phenyl)-5-bromo-4-cyano-1-methyl-1H-pyrrole-2-carboxylic acid ethyl ester | 851193-57-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 3-(4-benzyloxy-phenyl)-5-bromo-4-cyano-1-methyl-1H-pyrrole-2-carboxylic acid ethyl ester
• 英文别名: ethyl 3-(4-(benzyloxy)phenyl)-5-bromo-4-cyano-1-methyl-1H-pyrrole-2-carboxylate；ethyl 5-bromo-4-cyano-1-methyl-3-(4-phenylmethoxyphenyl)pyrrole-2-carboxylate
• CAS: 851193-57-2
• 化学式: C₂₂H₁₉BrN₂O₃
• 分子量: 439.308
• InChiKey: MTQVFJACIVUSLD-UHFFFAOYSA-N

物化性质

• 沸点：
  599.9±50.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  64.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-benzyloxy-phenyl)-5-bromo-4-cyano-1-methyl-1H-pyrrole-2-carboxylic acid ethyl ester 在 palladium dihydroxide 、 palladium catalyst Hartwig's ligand 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 1.0h， 生成 Ethyl 3-[4-(2-chlorophenyl)phenyl]-4-cyano-5-ethyl-1-methylpyrrole-2-carboxylate
  参考文献：
  名称：

  A novel class of positive allosteric modulators of AMPA receptors: Design, synthesis, and structure–activity relationships of 3-biphenyl-4-yl-4-cyano-5-ethyl-1-methyl-1H-pyrrole-2-carboxylic acid, LY2059346

  摘要：

  The synthesis and structure-activity relationship (SAR) of novel and highly potent positive allosteric modulators of AMPA receptors, 3-biphenyl-4-yl-4-cyano-5-ethyl-l-methy]-IH-pyrrole-2-carboxylic acid, are described. These studies indicated that higher potency was achieved with ortho substitution of the distal (D) phenyl of the 3-biphenyl ring and resulted in the discovery of a potent pyrrole LY2059346 (23q), that was selected for further evaluation in in vitro native tissue assays and in vivo experiments. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.012
• 作为产物：
  描述：

  3-(4-benzyloxy-phenyl)-2-(toluene-4-sulfonyl)-acrylonitrile 在 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 生成 3-(4-benzyloxy-phenyl)-5-bromo-4-cyano-1-methyl-1H-pyrrole-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  A novel class of positive allosteric modulators of AMPA receptors: Design, synthesis, and structure–activity relationships of 3-biphenyl-4-yl-4-cyano-5-ethyl-1-methyl-1H-pyrrole-2-carboxylic acid, LY2059346

  摘要：

  The synthesis and structure-activity relationship (SAR) of novel and highly potent positive allosteric modulators of AMPA receptors, 3-biphenyl-4-yl-4-cyano-5-ethyl-l-methy]-IH-pyrrole-2-carboxylic acid, are described. These studies indicated that higher potency was achieved with ortho substitution of the distal (D) phenyl of the 3-biphenyl ring and resulted in the discovery of a potent pyrrole LY2059346 (23q), that was selected for further evaluation in in vitro native tissue assays and in vivo experiments. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.012

文献信息

• [EN] PYRROLE AND PYRAZOLE DERIVATIVES AS POTENTIATORS OF GLUTAMATE RECEPTORS<br/>[FR] COMPOSES DE PYRROLE ET PYRAZOLE PRESENTANT UN EFFET POTENTIATEUR SUR LES RECEPTEURS DU GLUTAMATE
  申请人：LILLY CO ELI

  公开号：WO2005040110A1

  公开（公告）日：2005-05-06

  The present invention relates to pyrrole and pyrazole compounds of formula (I) and their pharmaceutically acceptable salts, and further relates to their use in treating schizophrenia, cognitive deficits associated with schizophrenia, Alzheimer's disease, dementia of the Alzheimer's type, mild cognitive impairment, or depression. The compounds act as potentiators on glutamate receptors, in particular AMPA and the GluR family.

  本发明涉及式(I)的吡咯和吡唑化合物及其药用可接受的盐，并且进一步涉及它们在治疗精神分裂症、与精神分裂症相关的认知缺陷、阿尔茨海默病、阿尔茨海默型痴呆、轻度认知障碍或抑郁症方面的应用。这些化合物作为谷氨酸受体的增强剂，特别是AMPA和GluR家族。
• Pyrrole and pyrazole derivatives as potentiators of glutamate receptors
  申请人：Albaugh Ann Pamela

  公开号：US20070066573A1

  公开（公告）日：2007-03-22

  The present invention relates to pyrrole and pyrazole compounds of formula (I) and their pharmaceutically acceptable salts, and further relates to their use in treating schizophrenia, cognitive deficits associated with schizophrenia, Alzheimer's disease, dementia of the Alzheimer's type, mild cognitive impairment, or depression. The compounds act as potentiators on glutamate receptors, in particular AMPA and the GluR family.

  本发明涉及式(I)的吡咯和吡唑化合物及其药学上可接受的盐，并进一步涉及它们在治疗精神分裂症、与精神分裂症相关的认知缺陷、阿尔茨海默病、阿尔茨海默型痴呆、轻度认知障碍或抑郁症方面的使用。这些化合物在谷氨酸受体上发挥增强剂作用，特别是AMPA和GluR家族。
• PYRROLE AND PYRAZOLE DERIVATIVES AS POTENTIATORS OF GLUTAMATE RECEPTORS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1670757A1

  公开（公告）日：2006-06-21
• US7625932B2
  申请人：——

  公开号：US7625932B2

  公开（公告）日：2009-12-01
• A novel class of positive allosteric modulators of AMPA receptors: Design, synthesis, and structure–activity relationships of 3-biphenyl-4-yl-4-cyano-5-ethyl-1-methyl-1H-pyrrole-2-carboxylic acid, LY2059346
  作者：Hamideh Zarrinmayeh、Eric Tromiczak、Dennis M. Zimmerman、Nancy Rankl、Ken H. Ho、Esteban Dominguez、Ana Castaño、Ana Escribano、Carmen Fernandez、Alma Jimenez、William J. Hornback、Eric S. Nisenbaum

  DOI：10.1016/j.bmcl.2006.07.012

  日期：2006.10

  The synthesis and structure-activity relationship (SAR) of novel and highly potent positive allosteric modulators of AMPA receptors, 3-biphenyl-4-yl-4-cyano-5-ethyl-l-methy]-IH-pyrrole-2-carboxylic acid, are described. These studies indicated that higher potency was achieved with ortho substitution of the distal (D) phenyl of the 3-biphenyl ring and resulted in the discovery of a potent pyrrole LY2059346 (23q), that was selected for further evaluation in in vitro native tissue assays and in vivo experiments. (c) 2006 Elsevier Ltd. All rights reserved.