[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 | 623577-65-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: [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
• 英文别名: [(1'R,4R,10'S)-1,1-dioxo-2-(2,2,2-trifluoroethyl)spiro[1,2,5-thiadiazolidine-4,13'-tricyclo[8.2.1.03,8]trideca-3(8),4,6-triene]-5'-yl] trifluoromethanesulfonate
• CAS: 623577-65-1
• 化学式: C₁₇H₁₈F₆N₂O₅S₂
• 分子量: 508.463
• InChiKey: ZBXYIPRWOXRXGY-GZBFAFLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  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 在 palladium diacetate 、 1,3-双(二苯基膦)丙烷 、 四丁基氟化铵 、 三溴化磷 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 (1'R,4R,10'S)-5'-[(E)-3-(4-methylpiperidin-1-yl)prop-1-enyl]-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：

  Cyclic sulfamide γ-secretase inhibitors

  摘要：

  A novel series of N-alkyl-substituted cyclic sulfamides were developed from a screening hit. Chemistries were developed which allowed surveys of N-alkyl groups and amines resulting in the identification of N-trifluoroethyl-substituted cyclic sulfamides with good in vitro and in vivo gamma-secretase activity. One compound with subnanomolar activity elicited a reduction in brain A beta 40 after oral dosing in APP-YAC mice. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.084
• 作为产物：
  描述：

  三环[8.2.1.03,8]十三-3,5,7-三烯-13-酮 在 palladium on activated charcoal 吡啶 、 lead(IV) acetate 、 ammonium hydroxide 、 lithium aluminium tetrahydride 、 硼烷 、 氢气 、 sodium hydride 、 磺酰胺 、 氯化铵 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 三氟乙酸 为溶剂， 反应 105.0h， 生成 [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
  参考文献：
  名称：

  Cyclic sulfamide γ-secretase inhibitors

  摘要：

  A novel series of N-alkyl-substituted cyclic sulfamides were developed from a screening hit. Chemistries were developed which allowed surveys of N-alkyl groups and amines resulting in the identification of N-trifluoroethyl-substituted cyclic sulfamides with good in vitro and in vivo gamma-secretase activity. One compound with subnanomolar activity elicited a reduction in brain A beta 40 after oral dosing in APP-YAC mice. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.084

文献信息

• [EN] HETEROARYL SUBSTITUTED SPIROCYCLIC SULFAMIDES FOR INHIBITION OF GAMMA SECRETASE<br/>[FR] SULFAMIDES SPIROCYCLIQUES SUBSTITUES PAR HETEROARYLE UTILISES COMME INHIBITEURS DE LA GAMMA-SECRETASE
  申请人：MERCK SHARP & DOHME

  公开号：WO2003093252A1

  公开（公告）日：2003-11-13

  Compounds of formula I are disclosed: in which X is a 5-membered heteroaryl ring and R is as defined herein. The compounds are inhibitors of the processing of APP by gamma-secretase, and hence are useful in the treatment or prevention of Alzheimer's disease.

  公式I的化合物已被披露：其中X是一个5-成员杂环芳基环，R如本文所定义。这些化合物是γ-分泌酶对APP加工的抑制剂，因此在治疗或预防阿尔茨海默病中是有用的。
• [EN] ALKENYL-SUBSTITUTED SPIROCYCLIC SULFAMIDES AS INHIBITORS OF GAMMA-SECRETASE<br/>[FR] SULFAMIDES SPIROCYCLIQUES SUBSTITUES PAR ALCENYLE UTILISES COMME INHIBITEURS DE LA GAMMA-SECRETASE
  申请人：MERCK SHARP & DOHME

  公开号：WO2003093251A1

  公开（公告）日：2003-11-13

  Compounds of formula (I) are disclosed: wherein R4 is an alkenyl group of defined structure. The compounds inhibit gamma-secretase, and hence are useful for treatment of Alzheimer's disease.

  公式（I）的化合物已被披露：其中R4是具有定义结构的烯基基团。这些化合物抑制γ-分泌酶，因此对治疗阿尔茨海默病有用。
• [EN] ALKYNYL-SUBSTITUTED SPIROCYCLIC SULFAMIDES FOR THE TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] SULFAMIDES SPIROCYCLIQUES SUBSTITUES PAR ALKYNYLE, DESTINES AU TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：MERCK SHARP & DOHME

  公开号：WO2003093253A1

  公开（公告）日：2003-11-13

  Compounds of formula (I) are disclosed. The compounds inhibit gamma-secretase and hence find use in treatment of Alzheimer's disease.

  公式（I）的化合物已被披露。这些化合物抑制γ-分泌酶，因此可用于治疗阿尔茨海默病。
• Heteroaryl substituted spirocyclic sulfamides for inhibition of gamma secretase
  申请人：Collins James Ian

  公开号：US20080070895A1

  公开（公告）日：2008-03-20

  Compounds of formula I are disclosed: in which X is a 5-membered heteroaryl ring and R is as defined herein. The compounds are inhibitors of the processing of APP by gamma-secretase, and hence are useful in the treatment or prevention of Alzheimer's disease.

  公开了式子I的化合物：其中X是5-成员的杂环芳基环，R如此定义。这些化合物是γ-分泌酶处理APP的抑制剂，因此在治疗或预防阿尔茨海默病方面是有用的。
• 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.