(1'R,4R,10'S)-5'-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-(2,2,2-trifluoroethyl)spiro[1,2,5-thiadiazolidine-4,13'-tricyclo[8.2.1.03,8]trideca-3(8),4,6-triene] 1,1-dioxide | 1159705-91-5

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: (1'R,4R,10'S)-5'-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-(2,2,2-trifluoroethyl)spiro[1,2,5-thiadiazolidine-4,13'-tricyclo[8.2.1.03,8]trideca-3(8),4,6-triene] 1,1-dioxide
• CAS: 1159705-91-5
• 化学式: C₂₁H₂₈BF₃N₂O₄S
• 分子量: 472.337
• InChiKey: RSYRXVGRZRFTOR-SQGPQFPESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.03
• 重原子数：
  32
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  76.2
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (1'R,4R,10'S)-5'-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-(2,2,2-trifluoroethyl)spiro[1,2,5-thiadiazolidine-4,13'-tricyclo[8.2.1.03,8]trideca-3(8),4,6-triene] 1,1-dioxide 、 1-methyl-3(5)-(4-fluorophenyl)-pyrazole nonaflate 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以100%的产率得到[6S,9R,11R]-2',3',4',5,5',6,7,8,9,10-decahydro-2-(5-(4-fluorophenyl)-1-methylpyrazol-3-yl)-5'-(2,2,2-trifluoroethyl)-spiro[6,9-methanobenzocyclooctene-11,3'-[1,2,5]thiadiazole] 1',1'-dioxide
  参考文献：
  名称：

  Novel Orally Bioavailable γ-Secretase Inhibitors with Excellent in Vivo Activity

  摘要：

  The development of potent gamma-secretase inhibitors having substituted heterocycles attached to a benzobicyclo[4.2.1]nonane core is described. This work led to the identification of [6S,9R,11R]-2',3',4',5,5',6,7,8,9,10-decahydro-2-(5-(4-fluorophenyl)-1-methyipyrazol-3-yl)-5'-(2,2,2-trifluoroethyl)spiro[6,9-methanobenzocyclooctene-11,3'-[1,2,5]thiadiazole] 1',1'-dioxide (16), which has excellent in vitro potency (0.06 nM) and which reduced amyloid-beta in APP-YAC mice with an ED50 of 1 mg/kg (po). 16 had a good pharmacokinetic profile in three preclinical species.

  DOI：

  10.1021/jm900056p
• 作为产物：
  描述：

  [6S,9R,11R]-2',3',4',5,5',6,7,8,9,10-decahydro-2-trifluoromethanesulphonate-5'-(2,2,2-trifluoroethyl)-spiro[6,9-methanobenzocyclooctene-11,3'-[1,2,5]thiadiazole] 1',1'-dioxide 、 联硼酸新戊二醇酯 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 作用下， 以 1,4-二氧六环 、 二甲基亚砜 为溶剂， 以88%的产率得到(1'R,4R,10'S)-5'-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-(2,2,2-trifluoroethyl)spiro[1,2,5-thiadiazolidine-4,13'-tricyclo[8.2.1.03,8]trideca-3(8),4,6-triene] 1,1-dioxide
  参考文献：
  名称：

  Novel Orally Bioavailable γ-Secretase Inhibitors with Excellent in Vivo Activity

  摘要：

  The development of potent gamma-secretase inhibitors having substituted heterocycles attached to a benzobicyclo[4.2.1]nonane core is described. This work led to the identification of [6S,9R,11R]-2',3',4',5,5',6,7,8,9,10-decahydro-2-(5-(4-fluorophenyl)-1-methyipyrazol-3-yl)-5'-(2,2,2-trifluoroethyl)spiro[6,9-methanobenzocyclooctene-11,3'-[1,2,5]thiadiazole] 1',1'-dioxide (16), which has excellent in vitro potency (0.06 nM) and which reduced amyloid-beta in APP-YAC mice with an ED50 of 1 mg/kg (po). 16 had a good pharmacokinetic profile in three preclinical species.

  DOI：

  10.1021/jm900056p

文献信息

• Novel Orally Bioavailable γ-Secretase Inhibitors with Excellent in Vivo Activity
  作者：Linda E. Keown、Ian Collins、Laura C. Cooper、Timothy Harrison、Andrew Madin、Jayesh Mistry、Michael Reilly、Mohamed Shaimi、Christopher J. Welch、Earl E. Clarke、Huw D. Lewis、Jonathan D. J. Wrigley、Jonathan D. Best、Fraser Murray、Mark S. Shearman

  DOI：10.1021/jm900056p

  日期：2009.6.11

  The development of potent gamma-secretase inhibitors having substituted heterocycles attached to a benzobicyclo[4.2.1]nonane core is described. This work led to the identification of [6S,9R,11R]-2',3',4',5,5',6,7,8,9,10-decahydro-2-(5-(4-fluorophenyl)-1-methyipyrazol-3-yl)-5'-(2,2,2-trifluoroethyl)spiro[6,9-methanobenzocyclooctene-11,3'-[1,2,5]thiadiazole] 1',1'-dioxide (16), which has excellent in vitro potency (0.06 nM) and which reduced amyloid-beta in APP-YAC mice with an ED50 of 1 mg/kg (po). 16 had a good pharmacokinetic profile in three preclinical species.