4-(1H-imidazol-5-ylmethylene)piperidine-1-carboxylic acid tert-butyl ester | 639089-43-3

• 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-(1H-imidazol-5-ylmethylene)piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-(1H-imidazol-5-ylmethylidene)piperidine-1-carboxylate
• CAS: 639089-43-3
• 化学式: C₁₄H₂₁N₃O₂
• 分子量: 263.34
• InChiKey: NEZFHMXIWMJJEB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  58.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(1H-imidazol-5-ylmethylene)piperidine-1-carboxylic acid tert-butyl ester 在 盐酸 作用下， 反应 2.0h， 以45%的产率得到VUF 5510
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Conformationally Constrained Histamine H₃ Receptor Agonists

  摘要：

  Immepip, a conformationally constrained analogue of the histamine congener imbutamine, shows high affinity and functional activity on the human H-3 receptor. Using histamine and its homologues as prototypes, other rigid analogues containing either a piperidine or pyrrolidine ring in the side chain were synthesized and tested for their activities at the human H-3 receptor and the closely related H-4 receptor. In the series of piperidine containing analogues, immepip was found to be the most potent H-3 receptor agonist, whereas its propylene analogue 13a was identified as a high-affinity neutral antagonist for the human H-3 receptor. Moreover, replacement of the piperidine ring of immepip by a pyrrolidine ring led to a pair of enantiomers that show a distinct stereoselectivity at the human H-3 and H-4 receptor.

  DOI：

  10.1021/jm030905y
• 作为产物：
  描述：

  4-[(1-tert-butoxycarbonyl-1H-imidazol-4-yl)methanesulfonyloxymethyl]piperidine-1-carboxylic acid tert-butyl ester 在 calcium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以85%的产率得到4-(1H-imidazol-5-ylmethylene)piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Conformationally Constrained Histamine H₃ Receptor Agonists

  摘要：

  Immepip, a conformationally constrained analogue of the histamine congener imbutamine, shows high affinity and functional activity on the human H-3 receptor. Using histamine and its homologues as prototypes, other rigid analogues containing either a piperidine or pyrrolidine ring in the side chain were synthesized and tested for their activities at the human H-3 receptor and the closely related H-4 receptor. In the series of piperidine containing analogues, immepip was found to be the most potent H-3 receptor agonist, whereas its propylene analogue 13a was identified as a high-affinity neutral antagonist for the human H-3 receptor. Moreover, replacement of the piperidine ring of immepip by a pyrrolidine ring led to a pair of enantiomers that show a distinct stereoselectivity at the human H-3 and H-4 receptor.

  DOI：

  10.1021/jm030905y

文献信息

• [EN] BRM TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE<br/>[FR] COMPOSÉS CIBLANT BRM ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：ARVINAS OPERATIONS INC

  公开号：WO2023097031A1

  公开（公告）日：2023-06-01

  The present disclosure relates to bifunctional compounds, which find utility as modulators of SMARCA2 or BRM (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel- Lindau E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，它们可用作 SMARCA2 或 BRM（靶蛋白）的调节剂。特别是，本公开涉及双功能化合物，其一端含有与 Von Hippel- Lindau E3 泛素连接酶结合的配体，另一端含有与靶蛋白结合的分子，从而使靶蛋白靠近泛素连接酶，以实现对靶蛋白的降解（和抑制）。本公开物具有与降解/抑制靶蛋白相关的广泛药理活性。本公开的化合物和组合物可以治疗或预防因目标蛋白聚集或积聚而导致的疾病或失调。
• Synthesis and Structure−Activity Relationships of Conformationally Constrained Histamine H₃ Receptor Agonists
  作者：Ruengwit Kitbunnadaj、Obbe P. Zuiderveld、Iwan J. P. De Esch、Roeland C. Vollinga、Remko Bakker、Martin Lutz、Anthony L. Spek、Emile Cavoy、Marie-France Deltent、Wiro M. P. B. Menge、Henk Timmerman、Rob Leurs

  DOI：10.1021/jm030905y

  日期：2003.12.1

  Immepip, a conformationally constrained analogue of the histamine congener imbutamine, shows high affinity and functional activity on the human H-3 receptor. Using histamine and its homologues as prototypes, other rigid analogues containing either a piperidine or pyrrolidine ring in the side chain were synthesized and tested for their activities at the human H-3 receptor and the closely related H-4 receptor. In the series of piperidine containing analogues, immepip was found to be the most potent H-3 receptor agonist, whereas its propylene analogue 13a was identified as a high-affinity neutral antagonist for the human H-3 receptor. Moreover, replacement of the piperidine ring of immepip by a pyrrolidine ring led to a pair of enantiomers that show a distinct stereoselectivity at the human H-3 and H-4 receptor.