1-tert-butyl 3-ethyl 4-(4-fluorophenyl)-5,6-dihydropyridine-1,3(2H)-dicarboxylate | 455954-86-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 1-tert-butyl 3-ethyl 4-(4-fluorophenyl)-5,6-dihydropyridine-1,3(2H)-dicarboxylate
• 英文别名: 1-O-tert-butyl 5-O-ethyl 4-(4-fluorophenyl)-3,6-dihydro-2H-pyridine-1,5-dicarboxylate
• CAS: 455954-86-6
• 化学式: C₁₉H₂₄FNO₄
• 分子量: 349.402
• InChiKey: UFCOVPOHSBZYBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-tert-butyl 3-ethyl 4-(4-fluorophenyl)-5,6-dihydropyridine-1,3(2H)-dicarboxylate 在 N-甲基吗啉 、 盐酸 、 甲醇 、 sodium hydroxide 、 sodium methylate 、 1-羟基苯并三唑 、 magnesium 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 (3R,4S)-N-[(2R)-4-[6-(4-chlorophenyl)sulfanyl-2-(4-methoxyphenyl)-3-oxopyridazin-4-yl]butan-2-yl]-4-(4-fluorophenyl)piperidine-3-carboxamide
  参考文献：
  名称：

  Design and syntheses of melanocortin subtype-4 receptor agonists. Part 2: Discovery of the dihydropyridazinone motif

  摘要：

  Optimization of the biological activity of a new class of non-peptidyl, pyridazinone derived human melanocortin subtype-4 receptor agonists is disclosed. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.033
• 作为产物：
  描述：

  1-苄基-4-哌啶酮-3-羧酸乙酯 在 palladium on activated charcoal (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 氢气 、 碳酸氢钠 、 N,N-二异丙基乙胺 、 sodium chloride 作用下， 以 乙醇 、 二氯甲烷 、 氯仿 、 水 为溶剂， -78.0~80.0 ℃ 、344.74 kPa 条件下， 生成 1-tert-butyl 3-ethyl 4-(4-fluorophenyl)-5,6-dihydropyridine-1,3(2H)-dicarboxylate
  参考文献：
  名称：

  Design and syntheses of melanocortin subtype-4 receptor agonists. Part 2: Discovery of the dihydropyridazinone motif

  摘要：

  Optimization of the biological activity of a new class of non-peptidyl, pyridazinone derived human melanocortin subtype-4 receptor agonists is disclosed. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.033

文献信息

• Acylated piperidine derivatives as melanocortin-4 receptor agonists
  申请人：——

  公开号：US20040097546A1

  公开（公告）日：2004-05-20

  Certain novel 4-substituted N-acylated piperidine derivatives are agonists of the human melanocortin receptor(s) and, in particular, are selective agonists of the human melanocortin-4 receptor (MC-4R). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the activation of MC-4R, such as obesity, diabetes, sexual dysfunction, including erectile dysfunction and female sexual dysfunction.

  某些新型4-取代N-酰化哌啶衍生物是人类黑素细胞素受体的激动剂，特别是人类黑素细胞素-4受体（MC-4R）的选择性激动剂。因此，它们可用于治疗、控制或预防对MC-4R激活敏感的疾病和障碍，如肥胖症、糖尿病、性功能障碍，包括勃起功能障碍和女性性功能障碍。
• Structural Modifications to Tetrahydropyridine-3-carboxylate Esters en Route to the Discovery of M₅-Preferring Muscarinic Receptor Orthosteric Antagonists
  作者：Guangrong Zheng、Andrew M. Smith、Xiaoqin Huang、Karunai L. Subramanian、Kiran B. Siripurapu、Agripina Deaciuc、Chang-Guo Zhan、Linda P. Dwoskin

  DOI：10.1021/jm301774u

  日期：2013.2.28

  The M-5 muscarinic acetylcholine receptor is suggested to be a potential pharmacotherapeutic target for the treatment of drug abuse. We describe herein the discovery of a series of M-5-preferring orthosteric antagonists based on the scaffold of 1,2,5,6-tetrahydropyridine-3-carboxylic acid. Compound 56, the most selective compound in this series, possesses an 11-fold selectivity for the M-5 over M-1 receptor and shows little activity at M-2-M-4. This compound, although exhibiting modest affinity (K-i = 2.24 mu M) for the [H-3]N-methylscopolamine binding site on the M-5 receptor, is potent (IC50 = 0.45 nM) in inhibiting oxotremorine-evoked [H-3]DA release from rat striatal slices. Further, a homology model of human M-5 receptor based on the crystal structure of the rat M-3 receptor was constructed, and docking studies of compounds 28 and 56 were performed in an attempt to understand the possible binding mode of these novel analogues to the receptor.
• EP1372653A4
  申请人：——

  公开号：EP1372653A4

  公开（公告）日：2005-10-05
• ACYLATED PIPERIDINE DERIVATIVES AS MELANOCORTIN-4 RECEPTOR AGONISTS
  申请人：Merck & Co., Inc.

  公开号：EP1372653A2

  公开（公告）日：2004-01-02
• US7015235B2
  申请人：——

  公开号：US7015235B2

  公开（公告）日：2006-03-21