((3-bromocyclopent-2-en-1-yl)oxy)(tert-butyl)dimethylsilane | 892145-14-1

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: ((3-bromocyclopent-2-en-1-yl)oxy)(tert-butyl)dimethylsilane
• 英文别名: ((3-Bromocyclopent-2-EN-1-YL)oxy)(tert-butyl)dimethylsilane；(3-bromocyclopent-2-en-1-yl)oxy-tert-butyl-dimethylsilane
• CAS: 892145-14-1
• 化学式: C₁₁H₂₁BrOSi
• 分子量: 277.277
• InChiKey: ZBLQIIBCBMQEOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.45
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  ((3-bromocyclopent-2-en-1-yl)oxy)(tert-butyl)dimethylsilane 在 叔丁基锂 、 氯化铵 作用下， 以 四氢呋喃 、 正戊烷 为溶剂， 反应 6.0h， 以72%的产率得到(2-环戊烯-1-氧基)二甲基(1,1-二甲基乙基)硅烷
  参考文献：
  名称：

  1,2-Bisanionic Coupling Approach to 2,3-Disubstituted Cyclopentenols and Cyclopentenones

  摘要：

  We describe a new approach to 2,3-disubstituted cyclopentenols and cyclopentenones through two consecutive regioselective additions of equal or different electrophiles to a cyclopentene bisanionic synthon. Indeed, on exposure to BuLi, 3-bromo-2-iodocyclopent-2-enol O-TBS ether undergoes iodine-lithium permutation with complete regioselectivity. Successive reaction of the monolithium anion with different C(sp(2))and C(sp(3))-electrophiles affords the corresponding 2-substituted-3-bromocyclopentenol derivative. Subsequent bromo-lithium exchange with t-BuLi, followed by reaction with an equal or different electrophile, affords the desired 2,3-disubstituted cyclopentenol.

  DOI：

  10.1021/ol060654y
• 作为产物：
  描述：

  (3-Bromo-2-iodo-cyclopent-2-enyloxy)-tert-butyl-dimethyl-silane 在 正丁基锂 、 氯化铵 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 4.2h， 以88%的产率得到((3-bromocyclopent-2-en-1-yl)oxy)(tert-butyl)dimethylsilane
  参考文献：
  名称：

  1,2-Bisanionic Coupling Approach to 2,3-Disubstituted Cyclopentenols and Cyclopentenones

  摘要：

  We describe a new approach to 2,3-disubstituted cyclopentenols and cyclopentenones through two consecutive regioselective additions of equal or different electrophiles to a cyclopentene bisanionic synthon. Indeed, on exposure to BuLi, 3-bromo-2-iodocyclopent-2-enol O-TBS ether undergoes iodine-lithium permutation with complete regioselectivity. Successive reaction of the monolithium anion with different C(sp(2))and C(sp(3))-electrophiles affords the corresponding 2-substituted-3-bromocyclopentenol derivative. Subsequent bromo-lithium exchange with t-BuLi, followed by reaction with an equal or different electrophile, affords the desired 2,3-disubstituted cyclopentenol.

  DOI：

  10.1021/ol060654y

文献信息

• Radiosynthesis and Evaluation of [¹¹C]3-Hydroxycyclopent-1-enecarboxylic Acid as Potential PET Ligand for the High-Affinity γ-Hydroxybutyric Acid Binding Sites
  作者：Claus H. Jensen、Hanne D. Hansen、Tina Bay、Stine B. Vogensen、Szabolcs Lehel、Louise Thiesen、Christoffer Bundgaard、Rasmus P. Clausen、Gitte M. Knudsen、Matthias M. Herth、Petrine Wellendorph、Bente Frølund

  DOI：10.1021/acschemneuro.6b00335

  日期：2017.1.18

  enecarboxylic acid (HOCPCA) seems like a suitable PET radiotracer candidate. Here, we report the 11C-labeling and subsequent evaluation of [11C]HOCPCA in a domestic pig, as a PET-radioligand for visualization of the high-affinity GHB binding sites in the live pig brain. To investigate the regional binding of HOCPCA in pig brain prior to in vivo PET studies, in vitro quantitative autoradiography on

  γ-羟基丁酸（GHB）是一种内源性神经活性物质，是拟议的神经递质，对低亲和力和高亲和力结合位点都具有亲和力。对高亲和力GHB结合位点具有高和特异性亲和力的放射性配体将是独特的工具，可以更全面地了解这种结合位点。3-羟基环戊-1-烯羧酸（HOCPCA）凭借其高的特异性亲和力和单羧酸盐转运蛋白（MCT1）介导的跨血脑屏障转运的药理学剂量，似乎是合适的PET放射性示踪剂候选物。在这里，我们报告11 C标记和对[ 11C] HOCPCA作为家畜猪中的PET-放射性配体，用于可视化活猪脑中的高亲和力GHB结合位点。为了在体内PET研究之前研究猪脑中HOCPCA的区域结合，使用[ 3 H] HOCPCA对猪脑切片进行了体外定量放射自显影。[ 11 C] HOCPCA的体内评估显示没有大脑摄取，可能是由于在[ 11 C] HOCPCA示踪剂量下MCT1转运蛋白对HOCPCA的摄取有限。
• Molecular Hybridization of Potent and Selective γ-Hydroxybutyric Acid (GHB) Ligands: Design, Synthesis, Binding Studies, and Molecular Modeling of Novel 3-Hydroxycyclopent-1-enecarboxylic Acid (HOCPCA) and <i>trans</i>-γ-Hydroxycrotonic Acid (T-HCA) Analogs
  作者：Jacob Krall、Claus Hatt Jensen、Francesco Bavo、Christina Birkedahl Falk-Petersen、Anne Stæhr Haugaard、Stine Byskov Vogensen、Yongsong Tian、Mia Nittegaard-Nielsen、Sara Björk Sigurdardóttir、Jan Kehler、Kenneth Thermann Kongstad、David E. Gloriam、Rasmus Prætorius Clausen、Kasper Harpsøe、Petrine Wellendorph、Bente Frølund

  DOI：10.1021/acs.jmedchem.7b01351

  日期：2017.11.9

  (HOCPCA) and the linear GHB analog trans-4-hydroxycrotonic acid (T-HCA). In general, all structural modifications performed on HOCPCA led to reduced affinity. In contrast, introduction of diaromatic substituents into the 4-position of T-HCA led to high-affinity analogs (medium nanomolar Ki) for the GHB high-affinity binding sites as the most high-affinity analogs reported to date. The SAR data formed the

  γ-羟基丁酸（GHB）是一种具有特定高亲和力结合位点的神经活性物质。为促进目标识别和配体优化，我们在此报告了针对这些结合位点的新型配体的全面结构亲和力关系研究。基于构象受限的3-羟基环戊-1-烯羧酸（HOCPCA）和线性GHB类似物反-4-羟基巴豆酸（T-HCA），使用了分子杂交策略。通常，对HOCPCA进行的所有结构修饰均导致亲和力降低。相反，将二芳族取代基引入T-HCA的4位可产生高亲和力类似物（中等纳摩尔浓度的K i），作为GHB高亲和力结合位点，是迄今为止报道的最高亲和力类似物。SAR数据构成了GHB配体的三维药效团模型的基础，该模型确定了对高亲和力结合具有重要预测意义的重要分子特征。这些发现在靶标表征和高亲和力GHB结合位点的配体鉴定的进一步过程中将是有价值的。
• New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-Affinity γ-Hydroxybutyrate (GHB) Binding Sites
  作者：Stine B. Vogensen、Aleš Marek、Tina Bay、Petrine Wellendorph、Jan Kehler、Christoffer Bundgaard、Bente Frølund、Martin H. F. Pedersen、Rasmus P. Clausen

  DOI：10.1021/jm4011719

  日期：2013.10.24

  3-Hydroxycyclopent-1-enecarboxylic acid (HOCPCA, 1) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of 1 together with a very efficient synthesis of [3H]-1 is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screening of 1 against different CNS targets establishes a high selectivity, and we demonstrate in vivo brain

  3-羟基环戊-1-烯羧酸(HOCPCA, 1 ) 是CNS 中高亲和力GHB 结合位点的有效配体。描述了1的改进合成以及[ 3 H]- 1的非常有效的合成。放射合成采用原位生成的三甲氧基硼酸锂。针对不同 CNS 目标筛选1建立了高选择性，我们证明了体内脑渗透。[ 3 H]- 1结合的体外表征显示出对高亲和力GHB结合位点的高度特异性。
• Bicyclo[3.1.0]hexyl urea melanin concentrating hormone (MCH) receptor-1 antagonists: Impacting hERG liability via aryl modifications
  作者：Mark D. McBriar、Henry Guzik、Sherry Shapiro、Ruo Xu、Jaroslava Paruchova、John W. Clader、Kim O’Neill、Brian Hawes、Steve Sorota、Michael Margulis、Kristal Tucker、Daniel J. Weston、Kathleen Cox

  DOI：10.1016/j.bmcl.2006.05.069

  日期：2006.8

  Herein, we report the discovery of an effective strategy to modulate liabilities related to affinity of previously disclosed bicyclohexane MCHR-1 antagonists for the hERG channel. This paper describes one of several strategies incorporated to limit hERG binding via modifications of a terminal aryl group in an otherwise promising bicyclohexyl urea series. (c) 2006 Elsevier Ltd. All rights reserved.
• Discovery of Orally Efficacious Melanin-Concentrating Hormone Receptor-1 Antagonists as Antiobesity Agents. Synthesis, SAR, and Biological Evaluation of Bicyclo[3.1.0]hexyl Ureas
  作者：Mark D. McBriar、Henry Guzik、Sherry Shapiro、Jaroslava Paruchova、Ruo Xu、Anandan Palani、John W. Clader、Kathleen Cox、William J. Greenlee、Brian E. Hawes、Timothy J. Kowalski、Kim O'Neill、Brian D. Spar、Blair Weig、Daniel J. Weston、Constance Farley、John Cook

  DOI：10.1021/jm050886n

  日期：2006.4.1

  Melanin-concentrating hormone (MCH) is a cyclic, nonadecapeptide expressed in the CNS of all vertebrates that regulates feeding behavior and energy homeostasis via interaction with the central melanocortin system. Regulation of this interaction results in modulation of food intake and body weight gain, demonstrating significant therapeutic potential for the treatment of obesity. The MCH-1 receptor (MCH-R1) has been identified as a key target in MCH regulation, as small molecule antagonists of MCH-R1 have demonstrated activity in vivo. Herein, we document our research in a bicyclo[3.1.0]hexyl urea series with particular emphasis on structure-activity relationships and optimization of receptor occupancy, measured both in vitro and via an ex vivo binding assay following an oral dosing regimen. Several compounds have been tested in vivo and exhibit oral efficacy in relevant acute rodent feeding models. In particular, 24u has proven efficacious in chronic rodent models of obesity, showing a statistically significant reduction in food intake and body weight over a 28 day study.