4-(3-Bromophenyl)-4-[4-(difluoromethoxy)phenyl]-1,3-thiazolidine-2,5-dithione | 871942-81-3

• 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: 4-(3-Bromophenyl)-4-[4-(difluoromethoxy)phenyl]-1,3-thiazolidine-2,5-dithione
• CAS: 871942-81-3
• 化学式: C₁₆H₁₀BrF₂NOS₃
• 分子量: 446.36
• InChiKey: ICWKBWLAZYCOMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(3-Bromophenyl)-4-[4-(difluoromethoxy)phenyl]-1,3-thiazolidine-2,5-dithione 在 叔丁基过氧化氢 、 ammonium hydroxide 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 14.0h， 生成 (8r)-8-[4-(Difluoromethoxy)phenyl]-3,3-Difluoro-8-[3-(3-Methoxyprop-1-Yn-1-Yl)phenyl]-2,3,4,8-Tetrahydroimidazo[1,5-A]pyrimidin-6-Amine
  参考文献：
  名称：

  Aminoimidazoles as BACE-1 inhibitors: The challenge to achieve in vivo brain efficacy

  摘要：

  The evaluation of a series of bicyclic aminoimidazoles as potent BACE-1 inhibitors is described. The crystal structures of compounds 14 and 23 in complex with BACE-1 reveal hydrogen bond interactions with the protein important for achieving potent inhibition. The optimization of permeability and efflux properties of the compounds is discussed as well as the importance of these properties for attaining in vivo brain efficacy. Compound (R)-25 was selected for evaluation in vivo in wild type mice and 1.5 h after oral co-administration of 300 mu mol/kg (R)-25 and efflux inhibitor GF120918 the brain A beta 40 level was reduced by 17% and the plasma A beta 40 level by 76%. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.079
• 作为产物：
  描述：

  在 potassium tert-butylate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 4-(3-Bromophenyl)-4-[4-(difluoromethoxy)phenyl]-1,3-thiazolidine-2,5-dithione
  参考文献：
  名称：

  Aminoimidazoles as BACE-1 inhibitors: The challenge to achieve in vivo brain efficacy

  摘要：

  The evaluation of a series of bicyclic aminoimidazoles as potent BACE-1 inhibitors is described. The crystal structures of compounds 14 and 23 in complex with BACE-1 reveal hydrogen bond interactions with the protein important for achieving potent inhibition. The optimization of permeability and efflux properties of the compounds is discussed as well as the importance of these properties for attaining in vivo brain efficacy. Compound (R)-25 was selected for evaluation in vivo in wild type mice and 1.5 h after oral co-administration of 300 mu mol/kg (R)-25 and efflux inhibitor GF120918 the brain A beta 40 level was reduced by 17% and the plasma A beta 40 level by 76%. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.079

文献信息

• Diphenylimidazopyrimidine and -imidazole amines as inhibitors of beta-secretase
  申请人：Malamas S. Michael

  公开号：US20050282826A1

  公开（公告）日：2005-12-22

  The present invention provides a compound of formula I and the use thereof for the therapeutic treatment, prevention or amelioration of a disease or disorder characterized by elevated β-amyloid deposits or β-amyloid levels in a patient.

  本发明提供了一种I式化合物及其用于治疗、预防或改善患有β-淀粉样蛋白沉积或患者体内β-淀粉样蛋白水平升高所特征的疾病或障碍的用途。
• [EN] DIPHENYLIMIDAZOPYRIMIDINE AND -IMIDAZOLE AMINES AS INHIBITORS OF B-SECRETASE<br/>[FR] DIPHENYLIMIDAZOPYRIMIDINE ET -IMIDAZOLE AMINES UTILISEES COMME INHIBITEURS DE B-SECRETASE
  申请人：WYETH CORP

  公开号：WO2006009655A1

  公开（公告）日：2006-01-26

  The present invention provides a compound of formula (I) and the use thereof for the therapeutic treatment, prevention or amelioration of a disease or disorder characterized by elevated ß-amyloid deposits or ß-amyloid levels in a patient.

  本发明提供了化合物(I)的公式以及其在治疗、预防或改善患有ß-淀粉样蛋白沉积或ß-淀粉样蛋白水平升高的疾病或障碍中的应用。
• DIPHENYLIMIDAZOLYL COMPOUNDS AS INHIBITORS OF beta-SECRETASE
  申请人：Malamas Michael S.

  公开号：US20090042912A1

  公开（公告）日：2009-02-12

  The present invention provides a compound of formula I and the use thereof for the therapeutic treatment, prevention or amelioration of a disease or disorder characterized by elevated β-amyloid deposits or β-amyloid levels in a patient.

  本发明提供了一种公式I的化合物及其用于治疗、预防或改善患有β-淀粉样沉积物或患者β-淀粉样水平升高的疾病或障碍的用途。
• US7456186B2
  申请人：——

  公开号：US7456186B2

  公开（公告）日：2008-11-25
• Aminoimidazoles as BACE-1 inhibitors: The challenge to achieve in vivo brain efficacy
  作者：Britt-Marie Swahn、Jörg Holenz、Jacob Kihlström、Karin Kolmodin、Johan Lindström、Niklas Plobeck、Didier Rotticci、Fernando Sehgelmeble、Marie Sundström、Stefan von Berg、Johanna Fälting、Biljana Georgievska、Susanne Gustavsson、Jan Neelissen、Margareta Ek、Lise-Lotte Olsson、Stefan Berg

  DOI：10.1016/j.bmcl.2012.01.079

  日期：2012.3

  The evaluation of a series of bicyclic aminoimidazoles as potent BACE-1 inhibitors is described. The crystal structures of compounds 14 and 23 in complex with BACE-1 reveal hydrogen bond interactions with the protein important for achieving potent inhibition. The optimization of permeability and efflux properties of the compounds is discussed as well as the importance of these properties for attaining in vivo brain efficacy. Compound (R)-25 was selected for evaluation in vivo in wild type mice and 1.5 h after oral co-administration of 300 mu mol/kg (R)-25 and efflux inhibitor GF120918 the brain A beta 40 level was reduced by 17% and the plasma A beta 40 level by 76%. (c) 2012 Elsevier Ltd. All rights reserved.