1-tert-butoxycarbonyl-4-{2-[hydroxy(1-methyl-1H-imidazol-2-yl)methyl]phenyl}piperazine | 444582-74-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-tert-butoxycarbonyl-4-{2-[hydroxy(1-methyl-1H-imidazol-2-yl)methyl]phenyl}piperazine
• 英文别名: 1-Boc-4-{2-[Hydroxy-(1-methyl-1H-imidazol-2-yl)-methyl]-phenyl}-piperazine；tert-butyl 4-[2-[hydroxy-(1-methylimidazol-2-yl)methyl]phenyl]piperazine-1-carboxylate
• CAS: 444582-74-5
• 化学式: C₂₀H₂₈N₄O₃
• 分子量: 372.467
• InChiKey: NVPNYLKBMOLKOW-UHFFFAOYSA-N

物化性质

• 沸点：
  573.5±50.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  70.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-tert-butoxycarbonyl-4-{2-[hydroxy(1-methyl-1H-imidazol-2-yl)methyl]phenyl}piperazine 在 偶氮二异丁腈 、 三正丁基氢锡 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Novel Arylpiperazines as Potent and Selective Agonists of the Melanocortin Subtype-4 Receptor

  摘要：

  The melanocortin receptors have been implicated as potential targets for a number of important therapeutic indications, including inflammation, sexual dysfunction, and obesity. We identified compound 1, an arylpiperazine attached to the dipeptide H-D-Tic-D-p-Cl-Phe-OH, as a novel melanocortin subtype-4 receptor (MC4R) agonist through iterative directed screening of nonpeptidyl G-protein-coupled receptor biased libraries. Structure-activity relationship (SAR) studies demonstrated that substitutions at the ortho position of the aryl ring improved binding and functional potency. For example, the o-isopropyl-substituted compound 29 (K-i = 720 nM) possessed 9-fold better binding affinity compared to the unsubstituted aryl ring (K-i = 6600 nM). Sulfonamide 39 (K-i = 220 nM) fills this space with a polar substituent, resulting in a further 2-fold improvement in binding affinity. The most potent compounds such as the diethylamine 44 (K-i = 60 nM) contain a basic group at this position. Basic heterocycles such as the imidazole 50 (K-i = 110 nM) were similarly effective. We also demonstrated good oral bioavailability for sulfonamide 39.

  DOI：

  10.1021/jm0304109
• 作为产物：
  描述：

  1-(2-苯甲腈)哌嗪 在 正丁基锂 、 二异丁基氢化铝 、 碳酸氢钠 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 正庚烷 为溶剂， 生成 1-tert-butoxycarbonyl-4-{2-[hydroxy(1-methyl-1H-imidazol-2-yl)methyl]phenyl}piperazine
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Novel Arylpiperazines as Potent and Selective Agonists of the Melanocortin Subtype-4 Receptor

  摘要：

  The melanocortin receptors have been implicated as potential targets for a number of important therapeutic indications, including inflammation, sexual dysfunction, and obesity. We identified compound 1, an arylpiperazine attached to the dipeptide H-D-Tic-D-p-Cl-Phe-OH, as a novel melanocortin subtype-4 receptor (MC4R) agonist through iterative directed screening of nonpeptidyl G-protein-coupled receptor biased libraries. Structure-activity relationship (SAR) studies demonstrated that substitutions at the ortho position of the aryl ring improved binding and functional potency. For example, the o-isopropyl-substituted compound 29 (K-i = 720 nM) possessed 9-fold better binding affinity compared to the unsubstituted aryl ring (K-i = 6600 nM). Sulfonamide 39 (K-i = 220 nM) fills this space with a polar substituent, resulting in a further 2-fold improvement in binding affinity. The most potent compounds such as the diethylamine 44 (K-i = 60 nM) contain a basic group at this position. Basic heterocycles such as the imidazole 50 (K-i = 110 nM) were similarly effective. We also demonstrated good oral bioavailability for sulfonamide 39.

  DOI：

  10.1021/jm0304109

文献信息

• Melanocortin receptor agonists
  申请人：——

  公开号：US20040092507A1

  公开（公告）日：2004-05-13

  The present invention relates to melanocortin receptor agonists of formula (I), which is useful in the treatment of obesity, diabetes and male and/or female sexual dysfunction. 1

  本发明涉及公式（I）的黑色素皮质素受体激动剂，其在肥胖症、糖尿病和男性和/或女性性功能障碍的治疗中有用。
• PIPERAZINE DERIVATIVES AS MELANOCORTIN RECEPTOR AGONISTS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1368340A1

  公开（公告）日：2003-12-10
• US7291619B2
  申请人：——

  公开号：US7291619B2

  公开（公告）日：2007-11-06
• [EN] MELANOCORTIN RECEPTOR AGONISTS<br/>[FR] DERIVES DE PIPERAZINE AGONISTES DU RECEPTEUR DE LA MELANOCORTINE
  申请人：LILLY CO ELI

  公开号：WO2002059108A1

  公开（公告）日：2002-08-01

  The present invention relates to melanocortin receptor agonists of formula (I), which is useful in the treatment of obesity, diabetes and male and/or female sexual dysfunction.