3,4-二氢-2H-螺[萘-1,4'-哌啶] | 134697-64-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 中文名称: 3,4-二氢-2H-螺[萘-1,4'-哌啶]
• 英文名称: 4-(tetralinyl)piperidine
• 英文别名: spiro[1,2,3,4-tetrahydronaphthalene-1,4-piperidine]；3,4-dihydro-2H-spiro[naphthalene-1,4'-piperidine]；spiro[piperidine-4,1'-tetralin]；3,4-dihydrospiro(naphthalene-1(2H),4'-piperidine)；spiro[2,3-dihydro-1H-naphthalene-4,4'-piperidine]
• CAS: 134697-64-6
• 化学式: C₁₄H₁₉N
• 分子量: 201.312
• InChiKey: PLWMBYBVKVUTBR-UHFFFAOYSA-N

物化性质

• 沸点：
  326.0±31.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3,4-二氢-2H-螺[萘-1,4'-哌啶] 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 1'-(thiophen-2-ylmethyl)spiro[2,3-dihydro-1H-naphthalene-4,4'-piperidine]
  参考文献：
  名称：

  Spiropiperidines as high-affinity, selective .sigma. ligands.

  摘要：

  A variety of achiral conformationally restricted spirocyclic piperidines have been prepared in an attempt to investigate the functional role of the central sigma-recognition site. All the compounds possessed a lipophilic N-substituent incorporating either a tetralin, indan, or benzocycloheptane skeleton. Their in vitro affinity at the sigma-site was assessed in radioligand displacement experiments with guinea pig cerebellum homogenates using the sigma-specific radioligand [H-3]-N,N'-di-o-tolyguanidine ([H-3]-DTG, [H-3]-6). A study of the structure-activity relationships identified the N-butyl and N-dimethylallyl substituents as the optimum groups for high affinity and selectivity at the sigma-site (e.g., 3,4-dihydro-1'-(3-methylbut-2-enyl)spiro[1H-indene-1,4'-piperidine] (48), pIC50 = 8.9 vs [3H]-6 and greater than 10000-fold selective over the dopamine D2 receptor). Such compounds are amongst the highest affinity sigma-ligands reported to date, with excellent selectivity over the dopamine D2 receptor, and may serve as at useful tool for exploring the physiological role of the sigma-site.

  DOI：

  10.1021/jm00089a013
• 作为产物：
  描述：

  β-四氢萘酮 在 palladium dihydroxide 氢氧化钾 、 甲酸 、 potassium tert-butylate 、 氢气 、 一水合肼 作用下， 以 乙醇 、 二甲基亚砜 、 叔丁醇 、 二乙二醇 为溶剂， 反应 25.0h， 生成 3,4-二氢-2H-螺[萘-1,4'-哌啶]
  参考文献：
  名称：

  Spiropiperidines as high-affinity, selective .sigma. ligands.

  摘要：

  A variety of achiral conformationally restricted spirocyclic piperidines have been prepared in an attempt to investigate the functional role of the central sigma-recognition site. All the compounds possessed a lipophilic N-substituent incorporating either a tetralin, indan, or benzocycloheptane skeleton. Their in vitro affinity at the sigma-site was assessed in radioligand displacement experiments with guinea pig cerebellum homogenates using the sigma-specific radioligand [H-3]-N,N'-di-o-tolyguanidine ([H-3]-DTG, [H-3]-6). A study of the structure-activity relationships identified the N-butyl and N-dimethylallyl substituents as the optimum groups for high affinity and selectivity at the sigma-site (e.g., 3,4-dihydro-1'-(3-methylbut-2-enyl)spiro[1H-indene-1,4'-piperidine] (48), pIC50 = 8.9 vs [3H]-6 and greater than 10000-fold selective over the dopamine D2 receptor). Such compounds are amongst the highest affinity sigma-ligands reported to date, with excellent selectivity over the dopamine D2 receptor, and may serve as at useful tool for exploring the physiological role of the sigma-site.

  DOI：

  10.1021/jm00089a013

文献信息

• Orally active, nonpeptide oxytocin antagonists
  作者：Ben E. Evans、James L. Leighton、Kenneth E. Rittle、Kevin F. Gilbert、George F. Lundell、Norman P. Gould、Doug W. Hobbs、Robert M. DiPardo、Daniel F. Veber、Douglas J. Pettibone、Bradley V. Clineschmidt、Paul S. Anderson、Roger M. Freidinger

  DOI：10.1021/jm00099a020

  日期：1992.10

  The first nonpeptide antagonists of the neurohypophyseal hormone, oxytocin (OT) are described. Derivatives of the spiroindenepiperidine ring system, these compounds include L-366,509, an orally bioavailable OT antagonist with good in vivo duration. The potential use of these agents for treatment of preterm labor and their significance as new nonpeptide ligands for peptide receptors are discussed.

  描述了神经下垂体激素催产素（OT）的第一个非肽拮抗剂。这些化合物是螺茚并哌啶环系统的衍生物，包括L-366509，这是一种口服生物可利用的OT拮抗剂，在体内具有良好的持续时间。讨论了这些药物在治疗早产中的潜在用途及其作为肽受体新的非肽配体的重要性。
• INHIBITORS OF 11BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1
  申请人：Claremon David A.

  公开号：US20110034455A1

  公开（公告）日：2011-02-10

  This invention relates to novel compounds of the Formula (I*), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11β-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of Cortisol in a cell or the inhibition of the conversion of cortisone to Cortisol in a cell.

  这项发明涉及到式(I*)的新化合物，其药用盐以及药物组合物，这些化合物对于治疗与哺乳动物中11β-HSD1的调节或抑制相关的疾病是有用的。该发明还涉及这些新化合物的药物组合物和它们在细胞中减少或控制皮质醇的产生或抑制皮质醇酮转化为皮质醇的方法。
• Spirocyclic nitriles as protease inhibitors
  申请人：Schudok Manfred

  公开号：US20090275523A1

  公开（公告）日：2009-11-05

  The invention relates to substituted carbo- and heterocyclic spiro compounds of the formula Ia which inhibit thiol proteases, to processes for their preparation and to the use thereof as medicaments.

  这项发明涉及公式Ia的取代碳氢和杂环螺环化合物，其抑制硫醇蛋白酶，以及它们的制备方法和用作药物的用途。
• Design and Synthesis of Novel α₁_a Adrenoceptor-Selective Antagonists. 2. Approaches To Eliminate Opioid Agonist Metabolites via Modification of Linker and 4-Methoxycarbonyl-4-phenylpiperidine Moiety
  作者：T. G. Murali Dhar、Dhanapalan Nagarathnam、Mohammad R. Marzabadi、Bharat Lagu、Wai C. Wong、George Chiu、Sriram Tyagarajan、Shou Wu Miao、Fengqi Zhang、Wanying Sun、Dake Tian、Quanrong Shen、Jack Zhang、John M. Wetzel、Carlos Forray、Raymond S. L. Chang、Theodore P. Broten、Terry W. Schorn、Tsing Bao Chen、Stacy O'Malley、Richard Ransom、Kathryn Schneck、Robert Bendesky、Charles M. Harrell、Kamlesh P. Vyas、Kanyin Zhang、John Gilbert、Douglas J. Pettibone、Michael A. Patane、Mark G. Bock、Roger M. Freidinger、Charles Gluchowski

  DOI：10.1021/jm990201h

  日期：1999.11.1

  by modification of the linker or finding alternative piperidine moieties which when cleaved as a consequence of metabolism would not give rise to mu-opioid activity. Modification of the linker gave several compounds with good alpha(1a) binding affinity (K(i) = < 1 nM) and selectivity (>300-fold over alpha(1b) and alpha(1d)). In vitro analysis in the microsomal assay revealed these modifications did

  先前我们已经将化合物1a描述为高亲和力亚型选择性alpha（1a）拮抗剂。化合物1a的体外和体内评估表明，其主要代谢产物为mu阿片类激动剂4-甲氧基羰基-4-苯基哌啶（3）。合成了几种二氢嘧啶酮类似物，其目的是通过修饰接头来使3的形成减至最少，或寻找替代的哌啶部分，当由于代谢作用而裂解时，其不会产生μ阿片样物质的活性。接头的修饰产生了几种具有良好的alpha（1a）结合亲和力（K（i）= <1 nM）和选择性（大于alpha（1b）和alpha（1d）的300倍）的化合物。微粒体测定法中的体外分析显示，这些修饰不会显着影响N-脱烷基和哌啶3的形成。第二种方法是 然而，产生了3个哌啶替代物，它们没有显示出明显的μ阿片样物质活性。这些化合物中的几种在α（1a）肾上腺素受体上保持了良好的亲和力，并且对alpha（1b）和alpha（1d）的选择性很高。例如，（+）-73和（+）-83的哌啶片段，
• Imidazole compounds having pharmaceutical activity towards the sigma receptor
  申请人：LABORATORIOS DEL DR. ESTEVE, S.A.

  公开号：EP1829867A1

  公开（公告）日：2007-09-05

  The present invention relates to compounds of formula (I), methods for their preparation, medicaments comprising these compounds as well their use in the manufacture of a medicament for the treatment of humans and animals.

  本发明涉及式(I)的化合物，其制备方法，包含这些化合物的药物，以及它们在制造用于治疗人类和动物的药物中的应用。