4-苄基-1-(2-丙炔基)哌啶 | 231947-12-9

• 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: 4-苄基-1-(2-丙炔基)哌啶
• 英文名称: 4-benzyl-1-prop-2-ynylpiperidine
• 英文别名: 4-benzyl-1-(2-propynyl)piperidine
• CAS: 231947-12-9
• 化学式: C₁₅H₁₉N
• mdl: MFCD12827844
• 分子量: 213.323
• InChiKey: HZWGCFCMXOQHTM-UHFFFAOYSA-N

物化性质

• 沸点：
  304.4±25.0 °C(Predicted)
• 密度：
  0.998±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.466
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-苄基-1-(2-丙炔基)哌啶 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 铁粉 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.5h， 生成 6-[3-(4-Benzyl-piperidin-1-yl)-prop-1-ynyl]-1-methyl-1,3-dihydro-benzoimidazol-2-one
  参考文献：
  名称：

  Subtype-Selective N-Methyl-d-Aspartate Receptor Antagonists:  Synthesis and Biological Evaluation of 1-(Heteroarylalkynyl)-4-benzylpiperidines

  摘要：

  4-[4-(4-Benzylpiperidin-1-yl)but-1-ynyl]phenol (8) and 4-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl phenol (9) are potent NR1A/2B receptor antagonists (IC50 values 0.17 and 0.10 mu M, respectively). Administered intraperitoneally, they both potentiated the activity of L-DOPA in the unilaterally 6-hydroxydopamine-lesioned (6-OHDA) rat, a model of Parkinson's disease. However, compound 9 was not active orally, likely due to rapid first-pass metabolism of the phenol moiety. The phenol was replaced by several bicyclic heterocyclic systems containing an NH group to function as a H-bond donor in the hope that these would be less likely to undergo rapid metabolism. In general, indoles, indazoles, benzotriazoles, indolones, and isatins gave analogues with weaker NR1A/2B activity than the parent phenols, while benzimidazolones and benzimidazolinones gave equipotent or more potent analogues. The preference for a para arrangement between the H-bond donor and the linking acetylene moiety was confirmed, and a propyne link was preferred over a butyne link. Substitution on the benzyl group or a 4-hydroxyl group on the piperidine had little effect on NR1A/2B potency; however, 4-hydroxypiperidines demonstrated slightly improved selectivity for NR1A/2B receptors versus alpha-1 adrenergic and dopamine D2 receptor affinity. From this study, 5-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl]-1,3-dihydrobenzo-imidazol-2-one (46b) was identified as a very potent, selective NR1A/2B receptor antagonist (IC50 value 0.0053 mu M). After oral administration at 10 and 30 mg/kg, 46b potentiated the effects of L-DOPA in the 6-OHDA-lesioned rat and seemed to have improved oral bioavailability but lower brain penetration compared to phenol 9.

  DOI：

  10.1021/jm000023o
• 作为产物：
  描述：

  4-苄基哌啶 、 3-溴丙炔 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 以55 %的产率得到4-苄基-1-(2-丙炔基)哌啶
  参考文献：
  名称：

  吲唑作为苯酚生物等排体：GluN2B 选择性 NMDA 受体拮抗剂的结构-亲和关系

  摘要：

  含有 GluN2B 亚基的 NMDA 受体的负变构调节可防止过度刺激，从而产生神经保护作用。由于显着的负变构调节剂的苯酚易于快速葡萄糖醛酸化，因此设想用吲唑替代其生物等排。合成的关键步骤是未保护的碘吲唑与炔丙基哌啶衍生物的 Sonogashira 反应。炔基部分的修饰允许引入几个官能团。合成的吲唑显示出非常高的 GluN2B 亲和力，但对 σ 受体的选择性有限。分子动力学模拟揭示了与类似酚类相同的与艾芬地尔结合位点的分子相互作用。在双电极电压钳实验中，对映体 3-(4-benzylpiperidin-1-yl)-1-(1 H -indazol-5-yl)propan-1-ols ( S )- 10a和 ( R )- 10a表现出比艾芬地尔更高的抑制活性。与酚类 GluN2B 拮抗剂相反，吲唑不与葡萄糖醛酸缀合。可以得出结论，有效的GluN2B拮抗剂的苯酚可以通过生物电子等排被吲唑取代，保留

  DOI：

  10.1021/acs.jmedchem.3c01161

文献信息

• Rapid Discovery and Structure−Activity Profiling of Novel Inhibitors of Human Immunodeficiency Virus Type 1 Protease Enabled by the Copper(I)-Catalyzed Synthesis of 1,2,3-Triazoles and Their Further Functionalization
  作者：Matthew Whiting、Jonathan C. Tripp、Ying-Chuan Lin、William Lindstrom、Arthur J. Olson、John H. Elder、K. Barry Sharpless、Valery V. Fokin

  DOI：10.1021/jm060754+

  日期：2006.12.1

  Building from the results of a computational screen of a range of triazole-containing compounds for binding efficiency to human immunodeficiency virus type 1 protease (HIV-1-Pr), a novel series of potent inhibitors has been developed. The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), which provides ready access to 1,4-disubstituted-1,2,3-triazoles, was used to unite a focused library of azide-containing

  根据一系列筛选结果，建立了一系列与人免疫缺陷病毒1型蛋白酶（HIV-1-Pr）结合效率高的含三唑化合物，现已开发出一系列新型的有效抑制剂。铜（I）催化的叠氮化物-炔烃环加成（CuAAC）可方便地使用1,4-二取代-1,2,3-三唑，用于将含叠氮化物片段的聚焦库与各种阵列结合在一起功能化的含炔烃的构建单元。与直接筛选粗反应产物相结合，该方法可快速鉴定先导结构，并容易实现叠氮化物和炔烃片段的优化。用一系列替代连接子取代三唑导致蛋白酶抑制作用大大降低。然而，
• Click Chemistry-Facilitated Structural Diversification of Nitrothiazoles, Nitrofurans, and Nitropyrroles Enhances Antimicrobial Activity against Giardia lamblia
  作者：Wan Jung Kim、Keith A. Korthals、Suhua Li、Christine Le、Jarosław Kalisiak、K. Barry Sharpless、Valery V. Fokin、Yukiko Miyamoto、Lars Eckmann

  DOI：10.1128/aac.02397-16

  日期：2017.6

  to new effective 5-nitroimidazole drugs that can combat nitro drug resistance, but the full potential of nitroheterocycles other than imidazole to yield effective new antigiardial agents has not been explored. Here, we generated derivatives of two clinically utilized nitroheterocycles, nitrothiazole and nitrofuran, as well as a third heterocycle, nitropyrrole, which is related to nitroimidazole but has

  贾第鞭毛虫是腹泻病的重要且普遍存在的原因。治疗贾第鞭毛虫病的主要药物是硝基杂环药物，尤其是咪唑，甲硝唑和替硝唑以及噻唑硝唑尼特。尽管这些药物通常都很有效，但在多达20％的病例中会出现治疗失败，并且体内和体外均显示出耐药性。先前的研究表明，咪唑核心的侧链修饰可导致产生新的有效的5-硝基咪唑药物，可以对抗硝基药物耐药性，但尚未探索除咪唑以外的硝基杂环化合物产生有效的新抗真菌药的全部潜力。在这里，我们生成了两个临床上使用的硝基杂环，硝噻唑和硝基呋喃以及第三个杂环的硝基吡咯的衍生物，它与硝基咪唑有关，但尚未作为抗菌药物支架进行系统研究。点击化学被用来合成442种具有广泛侧链修饰的新型硝基杂环化合物。针对代表性的G.lamblia菌株筛选该文库显示了广泛的体外活性，其中许多化合物相对于参考药物均显示出优异的活性，并且一些化合物显示出超过100倍的效力增强和克服了现有甲硝唑形式的能力反抗。大多数新化合物都没有表现出对人类细胞的细胞毒性，
• Synthesis of3H and14C labeled (S)-3-(5-chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indol-2-one, maxipost?. An agent for post-stroke neuroprotection
  作者：Douglas D. Dischino、Valentin K. Gribkoff、Piyasena Hewawasam、George M. Luke、J. Kent Rinehart、Tony L. Spears、John E. Starrett

  DOI：10.1002/jlcr.652

  日期：2003.2

  The syntheses of tritium labeled (S)-3-(5-chloro-2-[OC3H3]methoxyphenyl-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-1H-indol-2-one, and carbon-14 (S)-3-(5-chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-[2,3-14C2] indol-2-one are reported. The 3H-labeled compound was prepared in a two-step synthesis from C3H3I. The final product was purified via chiral HPLC to yield the desired enantiomer in a 4% radiochemical yield and a specific activity of 60 Ci/mmol. The 14C-labeled compound was prepared in a four-step synthesis from diethyl [carboxylate-14C1,2] oxalate. The final product was purified via chiral HPLC to yield the desired enantiomer in a 20% radiochemical yield and a specific activity of 28.4 μCi/mg. Copyright © 2002 John Wiley & Sons, Ltd.

  报告了氚标记的(S)-3-(5-氯-2-[OC3H3]甲氧基苯基)-1,3-二氢-3-氟-6-(三氟甲基)-1H-吲哚-2-酮和碳-14 (S)-3-(5-氯-2-甲氧基苯基)-1,3-二氢-3-氟-6-(三氟甲基)-2H-[2,3-14C2]吲哚-2-酮的合成。该 3H 标记化合物由 C3H3I 通过两步合成制备而成。最终产物经手性高效液相色谱纯化，得到了所需的对映体，放射化学收率为 4%，比活度为 60 Ci/mmol。14C 标记的化合物由[羧酸-14C1,2]草酸二乙酯经四步合成制备而成。最终产物经手性高效液相色谱纯化，得到了所需的对映体，放射化学收率为 20%，比活度为 28.4 μCi/mg。Copyright © 2002 John Wiley & Sons, Ltd. All Rights Reserved.
• EXPANDED THERAPEUTIC POTENTIAL IN NITROHETEROARYL ANTIMICROBIALS
  申请人：The Regents of the University of California

  公开号：US20160244435A1

  公开（公告）日：2016-08-25

  Disclosed herein are antimicrobial compounds compositions, pharmaceutical compositions, the use and preparation thereof. Some embodiments relate to imidazole, thiazole, and furan derivatives and their use as therapeutic agents.

  本文披露了抗微生物化合物组成物、制药组合物、其使用和制备方法。其中一些实施例涉及咪唑、噻唑和呋喃衍生物及其作为治疗剂的使用。
• Discovery of subtype-selective NMDA receptor ligands: 4-Benzyl-1-piperidinylalkynylpyrroles, pyrazoles and imidazoles as NR1a/2B antagonists
  作者：Jon L. Wright、Tracy F. Gregory、Peter A. Boxer、Leonard T. Meltzer、Kevin A. Serpa、Lawrence D. Wise、Soo Hong-Bae、Jin Cheng Huang、Christopher S. Konkoy、Ravindra B. Upasani、Edward R. Whittemore、Richard M. Woodward、Kevin C. Yang、Zhang-Lin Zhou

  DOI：10.1016/s0960-894x(99)00482-5

  日期：1999.10

  4-Benzyl-1-[4-(1 (H) under bar-imidazol-4-yl)but-3-ynyl]piperidine (8) has been identified as a potent antagonist of the NR1A/2B subtype of the NMDA receptor. When dosed orally, this compound potentiates the effects of L-DOPA, in the 6-hydroxydopamine-lesioned rat, a model of Parkinson's disease. (C) 1999 Elsevier Science Ltd. All rights reserved.