ethyl (1R,2R)-2-(4-bromo-2-fluorophenyl)cyclopropane-1-carboxylate | 934995-82-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl (1R,2R)-2-(4-bromo-2-fluorophenyl)cyclopropane-1-carboxylate
• CAS: 934995-82-1
• 化学式: C₁₂H₁₂BrFO₂
• 分子量: 287.128
• InChiKey: HEGCRMXRCHJXOH-VHSXEESVSA-N

物化性质

• 沸点：
  293.5±40.0 °C(Predicted)
• 密度：
  1.495±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (1R,2R)-2-(4-bromo-2-fluorophenyl)cyclopropane-1-carboxylate 在 lithium hydroxide 、 水 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 4.5h， 以94%的产率得到(1R,2R)-2-(4-Bromo-2-fluorophenyl)cyclopropane-1-carboxylic acid
  参考文献：
  名称：

  4-Oxo-1-3-Substituted Phenyl-1,4-Dihydro-1,8-Napthyridene-3-Carboxamide Phosphodiesterase-4 Inhibitor and a Method of Preparing Same

  摘要：

  该发明涉及结构式（22）的化合物，结构式（21）的晶型及其游离酸，包括这些化合物的药物组合物以及制备和使用这些化合物的方法。

  公开号：

  US20090105479A1
• 作为产物：
  描述：

  重氮乙酸乙酯 、 4-溴-2-氟-1-乙烯基苯 在 (4S)-4-tert-butyl-2-[2-[(4S)-4-tert-butyl-4,5-dihydro-1,3-oxazol-2-yl]propan-2-yl]-4,5-dihydro-1,3-oxazole;copper(1+);trifluoromethanesulfonate sodium tetrahydroborate 、 盐酸 、 水 作用下， 以 甲基叔丁基醚 、 乙醇 为溶剂， 反应 15.0h， 以85%的产率得到ethyl (1R,2R)-2-(4-bromo-2-fluorophenyl)cyclopropane-1-carboxylate
  参考文献：
  名称：

  4-oxo-1-(3-substituted phenyl)-1,4-dihydro-1,8-naphthyridine-3-carboxamide phosphodiesterase-4 inhibitor and a method of preparing same

  摘要：

  该发明涉及结构式（22）晶体形式的化合物，结构式（21）及其游离酸，包括这些化合物的药物组合物以及制备和使用这些化合物的方法。

  公开号：

  US20070099951A1

文献信息

• Discovery of MK-0952, a selective PDE4 inhibitor for the treatment of long-term memory loss and mild cognitive impairment
  作者：Michel Gallant、Renee Aspiotis、Stephen Day、Rebecca Dias、Daniel Dubé、Laurence Dubé、Richard W. Friesen、Mario Girard、Daniel Guay、Pierre Hamel、Zheng Huang、Patrick Lacombe、Sebastien Laliberté、Jean-François Lévesque、Susana Liu、Dwight Macdonald、Joseph Mancini、Donald W. Nicholson、Angela Styhler、Karen Townson、Kerry Waters、Robert N. Young、Yves Girard

  DOI：10.1016/j.bmcl.2010.09.087

  日期：2010.11

  The structure-activity relationship of a novel series of 8-biarylnaphthyridinones acting as type 4 phosphodiesterase (PDE4) inhibitors for the treatment of long-term memory loss and mild cognitive impairment is described herein. The manuscript describes a new paradigm for the development of PDE4 inhibitor targeting CNS indications. This effort led to the discovery of the clinical candidate MK-0952, an intrinsically potent inhibitor (IC50 = 0.6 nM) displaying limited whole blood activity (IC50 = 555 nM). Supporting in vivo results in two preclinical efficacy tests and one test assessing adverse effects are also reported. The comparative profiles of MK-0952 and two other Merck compounds are described to validate the proposed hypothesis. (C) 2010 Elsevier Ltd. All rights reserved.
• 4-Oxo-1-(3-substituted phenyl-1,4-dihydro-1,8-naphthyridine-3-carboxamide phosphodiesterase-4 inhibitor and a method of preparing same
  申请人：Dube Daniel

  公开号：US20080070940A1

  公开（公告）日：2008-03-20

  The invention is directed to a compound of the structural formula (22) crystal form of structural formulae (21) and its free acid, pharmaceutical compositions comprising these compounds and methods of preparing and using these compounds.
• [EN] A 4-OXO-1-(3-SUBSTITUTED PHENYL)-1,4-DIHYDRO-1,8-NAPHTHYRIDINE-3-CARBOXAMIDE PHOSPHODIESTERASE-4 INHIBITOR AND A METHOD OF PREPARING SAME<br/>[FR] INHIBITEUR DE 4-OXO-1-(3-PHENYLE SUBSTITUE)-1,4-DIHYDRO-1,8-NAPHTHYRIDINE-3-CARBOXAMIDE PHOSPHODIESTERASE-4 ET PROCEDE DE PREPARATION DE CELUI-CI
  申请人：MERCK & CO INC

  公开号：WO2007050576A2

  公开（公告）日：2007-05-03

  [EN] The invention is directed to a compound of the structural formula (22) (22) crystal form of structural formulae (21) and its free acid, pharmaceutical compositions comprising these compounds and methods of preparing and using these compounds.
  [FR] L'invention concerne un composé de formule structurale (22), une forme cristalline de formule structurale (21) et son acide libre, des compositions pharmaceutiques comprenant ces composés et des procédés de préparation et d'utilisation desdits composés.
• [EN] A 4-OXO-1- (3-SUBSTITUTED PHENYL) -1, 4-DIHYDRO-1, 8-NAPHTHYRIDINE-3-CARBOXAMIDE PHOSPHODIESTERASE-4-INHIBITOR AND A METHOD OF PREPARING SAME<br/>[FR] INHIBITEUR DE 4-OXO-1-(3-SUBSTITUE PHENYL)-1,4-DIHYDRO-1,8-NAPHTYRIDINE-3-CARBOXAMIDE PHOSPHODIESTERASE-4 ET SON PROCEDE DE FABRICATION
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2007048225A1

  公开（公告）日：2007-05-03

  [EN] The current application is directed to a compound of the structural formula (22), crystal form and crystalline free acid thereof, pharmaceutical compositions comprising these compounds and methods of preparing same These compounds are phosphodiesterase-4 inhibitors and are useful in the treatment of asthma and inflammation and are useful for the enhancement of cognition
  [FR] La présente invention concerne un composé de formule structurale (22), sa forme cristalline et son acide libre cristallin, des compositions pharmaceutiques comprenant ce composé et des procédés de préparation de ce composé. Ce composé constitue un inhibiteur de phosphodiestérase-4 et est utile pour le traitement de l'asthme et des inflammations, ainsi que pour l'amélioration de la cognition.