4-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl]-2-nitrobenzeneamine | 302799-84-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl]-2-nitrobenzeneamine
• 英文别名: 4-[3-(4-Benzylpiperidin-1-yl)prop-1-ynyl]-2-nitroaniline
• CAS: 302799-84-4
• 化学式: C₂₁H₂₃N₃O₂
• 分子量: 349.433
• InChiKey: DQELTHMQFXAPMM-UHFFFAOYSA-N

物化性质

• 沸点：
  523.4±50.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl]-2-nitrobenzeneamine 在 镍 作用下， 生成 4-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl]benzene-1,2-diamine
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1002/jlcr.652
• 作为产物：
  描述：

  4-苄基哌啶 在 四(三苯基膦)钯 作用下， 生成 4-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl]-2-nitrobenzeneamine
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1002/jlcr.652

文献信息

• Subtype-Selective <i>N</i>-Methyl-<scp>d</scp>-Aspartate Receptor Antagonists:  Synthesis and Biological Evaluation of 1-(Heteroarylalkynyl)-4-benzylpiperidines
  作者：Jon L. Wright、Tracy F. Gregory、Suzanne R. Kesten、Peter A. Boxer、Kevin A. Serpa、Leonard T. Meltzer、Lawrence D. Wise、Stephen A. Espitia、Christopher S. Konkoy、Edward R. Whittemore、Richard M. Woodward

  DOI：10.1021/jm000023o

  日期：2000.9.1

  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.
• Synthesis, radiosynthesis and In vivo evaluation of 5-[3-(4-Benzylpiperidin-1-yl)prop-1-ynyl]-1,3-dihydrobenzoimidazol-2-[11C]one, as a potent NR1A/2B subtype selective NMDA PET radiotracer
  作者：Gaëlle Roger、Béatrice Lagnel、Laurent Besret、Yann Bramoullé、Christine Coulon、Michelle Ottaviani、Michael Kassiou、Michel Bottlaender、Héric Valette、Frédéric Dollé

  DOI：10.1016/j.bmc.2003.09.036

  日期：2003.12

  Recently, a new series of potent and highly subtype-selective 1-(heteroarylalkynyl)-4-benzylpiperidine antagonists of the NMDA receptors has been described by Pfizer Laboratories. In this series, 5-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl]-1,3-dihydrobenzoimidazol-2-one (1) was identified as a selective antagonist for the NR1(A)/2B subtype, displaying IC50 values for inhibition of the NMDA responses of 5.3 nM for this subtype (compared to NR1(A)/2A: 35 muM and NR1(A)/2C > 100 muM) and was active in rat at a relatively low dosage (10 mg/kg po). Derivative 1 has been synthesized in four chemical steps in good overall yield and labelled with carbon-11 (T-1/2: 20.4min) at its benzoimidazolone ring using [C-11]phosgene. The pharmacological profile of [C-11]-1 was evaluated in vivo in rats with biodistribution studies and brain radioactivity monitored with intracerebral radiosensitive beta-microprobes. The brain uptake of [C-11]-1 was extremely low (0.07% I.D./mL on average at 30 min) and rather uniform across the different brain structures. This in vivo brain regional distribution of [C-11]-1 did not match with autoradiographic or binding data obtained with other NR2B subtype-selective NMDA ligands. Competition studies with ifenprodil (20 mg/kg, ip, 30 min before the radiotracer injection) failed to demonstrate specific binding of the radiotracer in the brain. In view of these results, and especially considering the low brain penetration of the radiotracer, [C-11]-1 does not have the required properties for imaging NMDA receptors using positron emission tomography. (C) 2003 Elsevier Ltd. All rights reserved.
• 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.