tert-butyl 4-(benzyl(ethyl)carbamoyl)piperidine-1-carboxylate | 896085-01-1

• 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: tert-butyl 4-(benzyl(ethyl)carbamoyl)piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-[benzyl(ethyl)carbamoyl]piperidine-1-carboxylate
• CAS: 896085-01-1
• 化学式: C₂₀H₃₀N₂O₃
• 分子量: 346.47
• InChiKey: GXBDBUMDDFGVJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(benzyl(ethyl)carbamoyl)piperidine-1-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 1.0h， 以100%的产率得到N-benzyl-N-ethylpiperidine-4-carboxamide hydrochloride
  参考文献：
  名称：

  Development of a Highly Potent, Novel M₅ Positive Allosteric Modulator (PAM) Demonstrating CNS Exposure: 1-((1H-Indazol-5-yl)sulfoneyl)-N-ethyl-N-(2-(trifluoromethyl)benzyl)piperidine-4-carboxamide (ML380)

  摘要：

  A functional high throughput screen identified a novel chemotype for the positive allosteric modulation (PAM) of the muscarinic acetylcholine receptor (mAChR) subtype 5 (M-5). Application of rapid analog, iterative parallel synthesis efficiently optimized M-5 potency to arrive at the most potent M-5 PAMs prepared to date and provided tool compound 8n (ML380) demonstrating modest CNS penetration (human M-5 EC50 = 190 nM, rat M-5 EC50 = 610 nM, brain to plasma ratio (K-p) of 0.36).

  DOI：

  10.1021/jm500995y
• 作为产物：
  描述：

  1-Boc-4-哌啶甲酸 在 potassium tert-butylate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl 4-(benzyl(ethyl)carbamoyl)piperidine-1-carboxylate
  参考文献：
  名称：

  作为基于 CCR5 拮抗剂的 HIV-1 进入抑制剂的新型 1,4-二取代哌啶/哌嗪衍生物的设计、合成和生物活性

  摘要：

  设计、合成了一系列新型 1,4-二取代哌啶/哌嗪衍生物，并评估了它们在 CEMX174 5.25M7 细胞中抗 HIV-1 Bal (R5) 感染的体外活性。大多数这些化合物显示出有效的抗 HIV-1 活性，IC 为纳摩尔水平。 -(4-氟苄基)哌嗪类似物盐酸盐表现出与 TAK-220 盐酸盐相似的抗 HIV-1 活性，但它具有更好的水溶性（25°C 磷酸钠缓冲液中 25mg/ml）和口服生物利用度(56%) 高于 TAK-220 盐酸盐（溶解度为 2mg/ml，口服生物利用度为 1.4%）。这些结果表明，盐酸盐可以作为开发新的抗 HIV-1 疗法或治疗和预防 HIV-1 感染的杀菌剂的更好先导物。

  DOI：

  10.1016/j.bmcl.2012.03.019

文献信息

• Design, synthesis, and biological evaluation of novel piperidine-4-carboxamide derivatives as potent CCR5 inhibitors
  作者：Suwen Hu、Quan Gu、Zhilong Wang、Zhiyong Weng、Yunrui Cai、Xiaowu Dong、Yongzhou Hu、Tao Liu、Xin Xie

  DOI：10.1016/j.ejmech.2013.11.013

  日期：2014.1

  Based on a putative 'Y shape' pharmacophore model of CCR5 inhibitors, a series of novel piperidine-4-carboxamide derivatives were designed and synthesized using a group-reverse strategy. Among synthesized target compounds, 16g (IC50 = 25.73 nM) and 16i (IC50 = 25.53 nM) showed equivalent inhibitory activity against CCR5 to that of the positive control maraviroc (IC50 = 25.43 nM) in calcium mobilization assay. Selected compounds were further tested for their antiviral activity in HIV-1 single cycle assay. Two compounds, 16g and 16i, displayed antiviral activity with IC50 values of 73.01 nM and 94.10 nM, respectively. Additionally, the pharmacokinetic properties and inhibitory potency against hERG of 16g were evaluated, providing a foundation for ongoing optimization. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Development of a Highly Potent, Novel M₅ Positive Allosteric Modulator (PAM) Demonstrating CNS Exposure: 1-((1<i>H</i>-Indazol-5-yl)sulfoneyl)-<i>N</i>-ethyl-<i>N</i>-(2-(trifluoromethyl)benzyl)piperidine-4-carboxamide (ML380)
  作者：Patrick R. Gentry、Masaya Kokubo、Thomas M. Bridges、Meredith J. Noetzel、Hyekyung P. Cho、Atin Lamsal、Emery Smith、Peter Chase、Peter S. Hodder、Colleen M. Niswender、J. Scott Daniels、P. Jeffrey Conn、Craig W. Lindsley、Michael R. Wood

  DOI：10.1021/jm500995y

  日期：2014.9.25

  A functional high throughput screen identified a novel chemotype for the positive allosteric modulation (PAM) of the muscarinic acetylcholine receptor (mAChR) subtype 5 (M-5). Application of rapid analog, iterative parallel synthesis efficiently optimized M-5 potency to arrive at the most potent M-5 PAMs prepared to date and provided tool compound 8n (ML380) demonstrating modest CNS penetration (human M-5 EC50 = 190 nM, rat M-5 EC50 = 610 nM, brain to plasma ratio (K-p) of 0.36).
• Design, synthesis, and biological activity of novel 1,4-disubstituted piperidine/piperazine derivatives as CCR5 antagonist-based HIV-1 entry inhibitors
  作者：Ming-xin Dong、Lu Lu、Haitao Li、Xiaohua Wang、Hong Lu、Shibo Jiang、Qiu-yun Dai

  DOI：10.1016/j.bmcl.2012.03.019

  日期：2012.5

  A series of novel 1,4-disubstituted piperidine/piperazine derivatives were designed, synthesized and evaluated for their in vitro activities against HIV-1 Bal (R5) infection in CEMX174 5.25M7 cells. A majority of these compounds showed potent anti-HIV-1 activities with IC at nanomolar levels. -(4-Fluoro-benzyl)piperazine analog hydrochloride exhibited potency against HIV-1 activity similar to that of

  设计、合成了一系列新型 1,4-二取代哌啶/哌嗪衍生物，并评估了它们在 CEMX174 5.25M7 细胞中抗 HIV-1 Bal (R5) 感染的体外活性。大多数这些化合物显示出有效的抗 HIV-1 活性，IC 为纳摩尔水平。 -(4-氟苄基)哌嗪类似物盐酸盐表现出与 TAK-220 盐酸盐相似的抗 HIV-1 活性，但它具有更好的水溶性（25°C 磷酸钠缓冲液中 25mg/ml）和口服生物利用度(56%) 高于 TAK-220 盐酸盐（溶解度为 2mg/ml，口服生物利用度为 1.4%）。这些结果表明，盐酸盐可以作为开发新的抗 HIV-1 疗法或治疗和预防 HIV-1 感染的杀菌剂的更好先导物。