Tert-butyl 4-[(benzylideneamino)methyl]piperidine-1-carboxylate | 144222-21-9

• 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-[(benzylideneamino)methyl]piperidine-1-carboxylate
• CAS: 144222-21-9
• 化学式: C₁₈H₂₆N₂O₂
• 分子量: 302.417
• InChiKey: RLAULXFJLBPDKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Tert-butyl 4-[(benzylideneamino)methyl]piperidine-1-carboxylate 在 盐酸 、 potassium hydrogensulfate 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 4-amino-5-chloro-2-methoxy-N-((1-(6-oxo-6-phenylhexyl)piperidin-4-yl)methyl)benzamide
  参考文献：
  名称：

  Design and synthesis of orally active benzamide derivatives as potent serotonin 4 receptor agonist

  摘要：

  A series of 4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamide derivatives bearing an aralkylamino, alkylamino, benzoyl or phenylsulfonyl group at its side chain part at the I-position on the piperidine ring was synthesized. They were evaluated for serotonin 4 (5-HT4) receptor agonist activity by testing their ability to contract the isolated guinea-pig ascending colon. 4-Amino-5-chloro-2-methoxy-N-[1-[5-(1-methylindol-3-ylcarbonylamino)pentyl]piperidin-4-ylmethyl]benzamide (1a, Y-34959) and its related compounds possessed favorable pharmacological profiles for gastrointestinal motility. Unfortunately, the compound 1a showed low bioavailability when given orally presumably due to its poor intestinal absorption rate. Replacement of the 1-methylindol-3-yl carbonylamino moiety of 1a with an aralkylamino (or alkylamino) group did not improve the intestinal absorption rate. Replacement of the 1-methylindol-3-ylcarbonylamino moiety with a benzoyl or phenylsulfonyl group increased the intestinal absorption rate compared with 1a. These compounds revealed good pharmacological profiles for gastrointestinal motility and were superior to 1a in oral bioavailability. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00412-7
• 作为产物：
  描述：

  4-氨甲基哌啶 以 甲苯 为溶剂， 生成 Tert-butyl 4-[(benzylideneamino)methyl]piperidine-1-carboxylate
  参考文献：
  名称：

  可溶性环氧化物水解酶的构象受限抑​​制剂的合成和SAR。

  摘要：

  已经开发了一系列人可溶性环氧化物水解酶（sEH）的构象受限的抑制剂。所述化合物对重组sEH的抑制能力为4.2μM至1.1nM。N-（1-乙酰基哌啶-4-基）-N'-（金刚烷基-1-基）尿素（5a）是一种有效的抑制剂（IC（50）= 7.0 nM），在犬中也可口服生物利用。

  DOI：

  10.1016/j.bmcl.2006.07.009

文献信息

• Novel vitronectin receptor antagonist derivatives, method for preparing same, use thereof as medicines and pharmaceutical compositions containing same
  申请人：Ruxer Jean-Marie

  公开号：US20060052398A1

  公开（公告）日：2006-03-09

  A subject of the invention is the compounds of formula (I): in which R 1 , R 2 , R 3 , R 4 and G have the meanings indicated in the description, their preparation process, their use as medicaments having an antagonist activity on the vitronectin receptor and the pharmaceutical compositions containing them.

  本发明涉及以下式(I)化合物：其中R1、R2、R3、R4和G具有描述中指示的含义，它们的制备方法，作为对维脱内钠受体具有拮抗活性的药物的用途，以及含有它们的制药组合物。
• Diamine containing VLA-4 antagonists
  作者：Peter C. Astles、Neil V. Harris、Andrew D. Morley

  DOI：10.1016/s0968-0896(01)00132-8

  日期：2001.8

  Design and synthesis of a library as potential VLA-4 antagonists has been accomplished, based around a proposed pharmacophoric model. Compounds possessing submicromolar potency were identified and structure-activity relationships were seen across the library. Further derivatisation produced compounds with IC50'S < 10 nmol for inhibiting the VLA-4 mediated binding of fibronectin to RAMOS cells, providing an ideal starting point for a lead optimisation Programme. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Synthesis and SAR of conformationally restricted inhibitors of soluble epoxide hydrolase
  作者：Paul D. Jones、Hsing-Ju Tsai、Zung N. Do、Christophe Morisseau、Bruce D. Hammock

  DOI：10.1016/j.bmcl.2006.07.009

  日期：2006.10

  A series of conformationally restricted inhibitors of human soluble epoxide hydrolase (sEH) has been developed. Inhibition potency of the described compounds ranges from 4.2 microM to 1.1 nM against recombinant sEH. N-(1-Acetylpiperidin-4-yl)-N'-(adamant-1-yl) urea (5a) was found to be a potent inhibitor (IC(50) = 7.0 nM) that was also orally bioavailable in canines.

  已经开发了一系列人可溶性环氧化物水解酶（sEH）的构象受限的抑制剂。所述化合物对重组sEH的抑制能力为4.2μM至1.1nM。N-（1-乙酰基哌啶-4-基）-N'-（金刚烷基-1-基）尿素（5a）是一种有效的抑制剂（IC（50）= 7.0 nM），在犬中也可口服生物利用。
• Design and synthesis of orally active benzamide derivatives as potent serotonin 4 receptor agonist
  作者：S Sonda

  DOI：10.1016/s0968-0896(03)00412-7

  日期：2003.9.15

  A series of 4-amino-5-chloro-2-methoxy-N-(piperidin-4-ylmethyl)benzamide derivatives bearing an aralkylamino, alkylamino, benzoyl or phenylsulfonyl group at its side chain part at the I-position on the piperidine ring was synthesized. They were evaluated for serotonin 4 (5-HT4) receptor agonist activity by testing their ability to contract the isolated guinea-pig ascending colon. 4-Amino-5-chloro-2-methoxy-N-[1-[5-(1-methylindol-3-ylcarbonylamino)pentyl]piperidin-4-ylmethyl]benzamide (1a, Y-34959) and its related compounds possessed favorable pharmacological profiles for gastrointestinal motility. Unfortunately, the compound 1a showed low bioavailability when given orally presumably due to its poor intestinal absorption rate. Replacement of the 1-methylindol-3-yl carbonylamino moiety of 1a with an aralkylamino (or alkylamino) group did not improve the intestinal absorption rate. Replacement of the 1-methylindol-3-ylcarbonylamino moiety with a benzoyl or phenylsulfonyl group increased the intestinal absorption rate compared with 1a. These compounds revealed good pharmacological profiles for gastrointestinal motility and were superior to 1a in oral bioavailability. (C) 2003 Elsevier Ltd. All rights reserved.