7-苄基-3-硫杂-7-氮杂双环[3.3.1]壬烷-9-酮 | 89398-04-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 7-苄基-3-硫杂-7-氮杂双环[3.3.1]壬烷-9-酮
• 中文别名: 7-苯甲基-3-硫杂-7-氮杂二环[3.3.1]壬烷-9-酮；硼酸,B-[4-(1,3-二噁烷-2-基)苯基]-
• 英文名称: 7-Benzyl-3-thia-7-azabicyclo[3.3.1]nonan-9-one
• 英文别名: 7-benzyl-3-thia-7-azabicyclo<3.3.1>nonan-9-one；7-benzyl-7-aza-3-thiabicyclo<3.3.1>nonan-9-one；N-benzyl-3-thia-7-azabicyclo<3.3.1>nonan-9-one；N-benzyl-3-thia-7-azabicyclo[3.3.1]nonan-9-one；(rac)-7-benzyl-3-thia-7-aza-bicyclo[3.3.1]nonan-9-one
• CAS: 89398-04-9
• 化学式: C₁₄H₁₇NOS
• mdl: MFCD00795098
• 分子量: 247.361
• InChiKey: ONSHXQWGCKFQFZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-苄基-3-硫杂-7-氮杂双环[3.3.1]壬烷-9-酮 在 sodium azide 、 硫酸 作用下， 以 氯仿 为溶剂， 反应 8.0h， 以76%的产率得到7-Benzyl-3-thia-7,9-diazabicyclo<3.3.2>decan-10-one
  参考文献：
  名称：

  3,7,9-Triheterabicyclo[3.3.2]decan-10-ones: an unusual family of heterocycles obtained from 3,7-diheterabicyclo[3.3.1]nonan-9-ones

  摘要：

  A series of new 3,7,9-triheterabicyclo[3.3.2]decan-10-ones is reported for the first time. Members of the family of 3,7-diheterabicyclo[3.3.1]nonan-9-ones served as precursors of the title compounds. Spectral evidence suggests the 3,7,9-triheterabicyclo[3.3.2]decan-10-ones exist in a chair-boat (CB) reversible boat-chair (BC) equilibrium in solution. It is speculated that steric hindrance around the carbonyl group and possibly the variance in conformation BC versus CC of the individual 3,7-diheterabicydo-[3.3.1]nonan-9-one precursors in solution may influence the ease of oxygen and nitrogen insertion in the ring enlargement to give the title molecules. Confirmation that three members of the bicyclo[3.3.2] decan-10-ones exist in BC forms in the solid state was achieved via single crystal X-ray diffraction analysis for 7-benzyl-3-thia-7,9-diazabicyclo[3.3.2]decan-10-one (4a), 3,7-dibenzyl-3,7,9-triazabicyclo-[3.3.2]decan-10-one (4c), and 3,7-dibenzyl-9-oxa-3,7-diazabicyclo[3.3.2]decan-10-one (4d).

  DOI：

  10.1021/jo00079a009
• 作为产物：
  描述：

  苄胺 在 sodium hydroxide 、 paraformaldehyde 作用下， 以 甲醇 、 乙醚 、 水 、 Petroleum ether 为溶剂， 生成 7-苄基-3-硫杂-7-氮杂双环[3.3.1]壬烷-9-酮
  参考文献：
  名称：

  3-thia-7-azabicyclo(3.3.l)nonanes and derivatives as antiarrhythmic

  摘要：

  本文披露了3-Thia-7-azabicyclo(3.3.1)nonanes及其衍生物。给出了这些化合物的制备方法。同时，给出了它们作为抗心律失常药物的用途。

  公开号：

  US04581361A1

文献信息

• BRIDGED PIPERIDINE DERIVATIVES
  申请人：Baumann Karlheinz

  公开号：US20120225884A1

  公开（公告）日：2012-09-06

  The present invention relates to compounds of formula I hetaryl I, hetaryl II, R 1 , R 2 , R 3 , Y, m, and o or to pharmaceutically active acid addition salts thereof. The present compounds of formula I are modulators for amyloid beta and thus, they may be useful for the treatment or prevention of a disease associated with the deposition of β-amyloid in the brain, in particular Alzheimer's disease, and other diseases such as cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica and Down syndrome.

  本发明涉及式Ihetaryl I、hetaryl II、R1、R2、R3、Y、m和o的化合物，或其药用活性酸盐。式I的这些化合物是淀粉样蛋白β的调节剂，因此它们可能对治疗或预防与大脑中β-淀粉样蛋白沉积相关的疾病有用，特别是阿尔茨海默病，以及其他疾病，如脑淀粉样血管病、遗传性淀粉样脑出血、荷兰型（HCHWA-D）、多梗死性痴呆、拳击性痴呆和唐氏综合征。
• [EN] BRIDGED PIPERIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE PIPÉRIDINE PONTÉS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012116965A1

  公开（公告）日：2012-09-07

  The present invention relates to compounds of formula (l); hetaryl I is a five or six membered heteroaryl group, containing 1 to 3 heteroatoms, selected from S or N; hetaryl II is a six membered heteroaryl group, containing 1 to 3 heteroatoms, selected from S or N, or is a two membered ring system containing 1 to 4 heteroatoms selected from S, or N, wherein at least one ring is aromatic in nature; R1 is lower alkyl, lower alkoxy, lower alkyl substituted by halogen or halogen; R2 is lower alkyl, lower alkyl substituted by halogen, halogen, lower alkoxy, cycloalkyl substituted by lower alkyl or lower alkyl substituted by halogen, or is lower alkyl substituted by hydroxy, or is furyl, or is O-benzyl, (CH2)p-phenyl, optionally substituted by halogen, lower alkoxy, lower alkyl substituted by halogen, lower alkyl or by cyano; R3 is hydrogen or lower alkyl; Y is (CH2)n-, -CH2OCH2-, -CH2O-, CH2S-, -CH2SCH2- and is bonded to two of the ring carbon atoms, bonding being to either the ring carbon atoms a and b or the ring carbon atoms c and d; p is 0 or 1; m is 0, 1 or 2; if m is 2 then R1 may be the same or different; -75- n is 2 or 3; o is 0, 1 or 2, if o is 2, then R2 may be the same or different; or to pharmaceutically active acid addition salts thereof. The present compounds of formula I are modulators for amyloid beta and thus, they may be useful for the treatment or prevention of a disease associated with the deposition of β-amyloid in the brain, in particular Alzheimers disease, and other diseases such as cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica and Down syndrome.

  本发明涉及以下式（l）的化合物；hetaryl I 是一个含有1至3个杂原子（S或N）的五元或六元杂芳基团；hetaryl II 是一个含有1至3个杂原子（S或N）的六元杂芳基团，或者是一个含有1至4个杂原子（S或N）的两元环系统，其中至少一个环具有芳香性质；R1 是低碳基、低烷氧基、被卤素取代的低烷基或卤素；R2 是低碳基、被卤素取代的低烷基、卤素、低烷氧基、被低烷基取代的环烷基、或被卤素取代的低烷基，或者是被羟基取代的低烷基，或是呋喃基，或是O-苄基，（CH2）p-苯基，可选择地被卤素、低烷氧基、被卤素取代的低烷基、低烷基或氰基取代；R3 是氢或低碳基；Y 是（CH2）n-、-CH2OCH2-、-CH2O-、CH2S-、-CH2SCH2-，与两个环碳原子结合，结合到环碳原子a和b或环碳原子c和d之一；p 为0或1；m 为0、1或2；若m为2，则R1 可相同或不同；n 为2或3；o 为0、1或2，若o为2，则R2 可相同或不同；或其药用酸盐。本发明的式I化合物是淀粉样蛋白β的调节剂，因此可能对与大脑中β-淀粉样蛋白沉积相关的疾病的治疗或预防有用，特别是阿尔茨海默病，以及其他疾病，如脑淀粉样血管病、家族性脑出血伴淀粉样蛋白沉积、荷兰型（HCHWA-D）、多梗塞性痴呆、拳击性痴呆和唐氏综合征。
• Synthesis, Stereochemical, and Conformational Studies of Selected 3,7-Diheterabicyclo[3.3.1]nonan-9-ols: X-Ray Diffraction Analyses of 7-Benzyl-9-phenyl-3-oxa-7-azabicyclo[3.3.1]nonan-9-ol and 7-Benzyl-9-(4-<b> <i>N,N′</i> </b>-dimethylaminophenyl)-3-thia-7-azabicyclo[3.3.1]nonan-9-ol, a Rare Stable Chair–Boat Form With Trigonal Nitrogen
  作者：Kevin Tran、K. Darrell Berlin、Margaret A. Eastman、Elizabeth M. Holt、Randal Hallford、Valentina K. Yu、K. D. Praliev

  DOI：10.1080/10426500600867489

  日期：2007.1.1

  respective rings. The X-ray analyses demonstrated that the solid, bicyclic, oxygen-containing alcohol was in chair–chair form while the solid, bicyclic, sulfur-containing alcohol existed in chair–boat form. A tentative mechanism is that the Grignard reagent may coordinate with the oxygen atom and / or sulfur atom in a boat conformer of the bicyclic system prior to the attack from the “oxygen or sulfur sides

  通过对称取代的芳基格氏试剂在无水四氢呋喃或乙醚中对 3,7-二杂双环 [3.3.1]壬烷-9-酮 (3,7-DHBCN-9-ONES) 进行 1,2-加成的系统研究. 1,2-芳基格氏试剂与 7-benzyl-3-oxa-7-azabicyclo[3.3.1]nonan-9-one 和 7-benzyl-3-thia-7- 中 C-9 的羰基的加成azabicyclo[3.3.1]nonan-9-one 导致叔醇的形成，其中芳基“syn”与相应环中的氧或硫原子相连。X 射线分析表明，固体、双环、含氧醇呈椅-椅形式，而固体、双环、含硫醇以椅-船形式存在。
• Synthesis, conformational analysis, and antiarrhythmic properties of 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonan-9-one, 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonane hydroperchlorate, and 7-benzyl-9-phenyl-3-thia-7-azabicyclo[3.3.1]nonan-9-ol hydroperchlorate and derivatives. Single-crystal x-ray diffraction analysis and evidence for chair-chair and chair-boat conformers in the solid state
  作者：Bruce R. Bailey、K. Darrell Berlin、Elizabeth M. Holt、Benjamin J. Scherlag、Ralph Lazzara、Johannes Brachmann、Dick Van der Helm、Douglas R. Powell、Nantelle S. Pantaleo、Peter C. Ruenitz

  DOI：10.1021/jm00372a010

  日期：1984.6

  The synthesis of the title ketone has been completed via a type of Mannich reaction starting from 4- thianone . An X-ray diffraction analysis has revealed that the solid system is a chair-boat conformer with the sulfur atom in the boat portion of the bicyclic ring compound. Wolff- Kishner reduction of the ketone group gave 7-benzyl-3-thia-7-azabicyclo [3.3.1]nonane, which was isolated as the hydroperchlorate

  标题酮的合成已通过从4-噻酮开始的一种Mannich反应完成。X射线衍射分析表明，该固体系统是一个椅子-船形物，双环化合物的船形部分中有硫原子。酮基的Wolff-Kishner还原反应得到7-苄基-3-硫杂-7-氮杂双环[3.3.1]壬烷，将其分离为氢过氯酸盐。然而，盐的X射线衍射分析表明该固体是椅子-椅子构象物。将苯溴化镁加到酮中得到叔醇，其C-C6H5键相对于噻吩环是赤道的，而相对于哌啶环是轴向的。格氏试剂与酮的反应产生这种醇似乎是立体定向的。对该醇的氢高氯酸盐进行X射线分析证实该系统为固体形式的椅子形式。在结扎左前降支冠状动脉后产生心肌梗塞的麻醉杂种犬中筛选标题化合物的抗心律失常活性。迷走神经引起的窦性心律放电率的减慢被用来确定狗的潜在心室自动性，平均为164 +/- 27次/分钟。心室起搏开始于240至390 / min之间的速度。该技术导致了快速而持续的室性心动过速的诱导。在3和6
• BICYCLIC HETEROCYCLE DERIVATIVES AND THEIR USE AS MODULATORS OF THE ACTIVITY OF GPR119
  申请人：Xia Yan

  公开号：US20110212938A1

  公开（公告）日：2011-09-01

  The present invention relates to Bicyclic Heterocycle Derivatives, compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of GPR119 in a patient.

  本发明涉及双环杂环衍生物、包含双环杂环衍生物的组合物以及使用双环杂环衍生物治疗或预防患者的肥胖症、糖尿病、代谢紊乱、心血管疾病或与GPR119活性相关的疾病的方法。