3(S)-(6-methoxypyridin-3-yl)-3-{2-oxo-[3-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)propyl]imidazolidin-1-yl}propionic acid ethyl ester | 227963-56-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 3(S)-(6-methoxypyridin-3-yl)-3-{2-oxo-[3-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)propyl]imidazolidin-1-yl}propionic acid ethyl ester
• 英文别名: ethyl (3S)-3-(6-methoxypyridin-3-yl)-3-[2-oxo-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]imidazolidin-1-yl]propanoate
• CAS: 227963-56-6
• 化学式: C₂₅H₃₃N₅O₄
• 分子量: 467.568
• InChiKey: UQIUODATIHRDAN-NRFANRHFSA-N

物化性质

• 沸点：
  706.0±60.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  96.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3(S)-(6-methoxypyridin-3-yl)-3-{2-oxo-[3-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)propyl]imidazolidin-1-yl}propionic acid ethyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以93%的产率得到(3S)-3-(6-methoxypyridin-3-yl)-3-{2-oxo-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]imidazolidin-1-yl}propionic acid
  参考文献：
  名称：

  Nonpeptide α_vβ₃ Antagonists. 8. In Vitro and in Vivo Evaluation of a Potent α_vβ₃ Antagonist for the Prevention and Treatment of Osteoporosis

  摘要：

  3(S)-(6-Methoxypyridin-3-yl)-3-{2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)propyl]-imidazolidin-1-yl}propionic acid 6 was identified as a potent and selective antagonist of the alpha(v)beta(3) receptor. This compound has an excellent in vitro profile (IC50 = 0.08 nM), a significant unbound fraction in human plasma (12%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in three in vivo models of bone turnover, the compound was selected for clinical development. To support the ongoing metabolism and safety studies, a novel strategy was employed in which a series of oxidized derivatives of 6 were prepared by exposure of 6 (or the methyl ester) to chemical oxidizing agents. These products proved useful in the identification of active metabolites generated by either in vitro or in vivo metabolism.

  DOI：

  10.1021/jm030306r
• 作为产物：
  描述：

  2-甲氧基吡啶 在 palladium dihydroxide 盐酸 、 4-二甲氨基吡啶 、 氢氧化钾 、 正丁基锂 、 氢气 、 溴 、 sodium acetate 、 sodium cyanoborohydride 、 溶剂黄146 、 N,N-二异丙基乙胺 、 potassium bromide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 乙酸乙酯 、 1,2-二氯乙烷 、 异丙醇 为溶剂， 反应 65.25h， 生成 3(S)-(6-methoxypyridin-3-yl)-3-{2-oxo-[3-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)propyl]imidazolidin-1-yl}propionic acid ethyl ester
  参考文献：
  名称：

  Nonpeptide α_vβ₃ Antagonists. 8. In Vitro and in Vivo Evaluation of a Potent α_vβ₃ Antagonist for the Prevention and Treatment of Osteoporosis

  摘要：

  3(S)-(6-Methoxypyridin-3-yl)-3-{2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)propyl]-imidazolidin-1-yl}propionic acid 6 was identified as a potent and selective antagonist of the alpha(v)beta(3) receptor. This compound has an excellent in vitro profile (IC50 = 0.08 nM), a significant unbound fraction in human plasma (12%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in three in vivo models of bone turnover, the compound was selected for clinical development. To support the ongoing metabolism and safety studies, a novel strategy was employed in which a series of oxidized derivatives of 6 were prepared by exposure of 6 (or the methyl ester) to chemical oxidizing agents. These products proved useful in the identification of active metabolites generated by either in vitro or in vivo metabolism.

  DOI：

  10.1021/jm030306r

文献信息

• INTEGRIN RECEPTOR ANTAGONISTS
  申请人：MERCK & CO., INC.

  公开号：EP1040111B1

  公开（公告）日：2005-06-22
• INTEGRIN TARGETING AGENTS AND IN-VIVO AND IN-VITRO IMAGING METHODS USING THE SAME
  申请人：Rajopadhye Milind

  公开号：US20110165075A1

  公开（公告）日：2011-07-07

  The invention provides a family of agents that target integrins, which can be used as imaging agents and/or therapeutic agents. The agents can be used to image angiogenesis, inflammation or other physiological processes in a subject.
• US6017926A
  申请人：——

  公开号：US6017926A

  公开（公告）日：2000-01-25
• US9694089B2
  申请人：——

  公开号：US9694089B2

  公开（公告）日：2017-07-04
• Nonpeptide α_vβ₃ Antagonists. 8. In Vitro and in Vivo Evaluation of a Potent α_vβ₃ Antagonist for the Prevention and Treatment of Osteoporosis
  作者：John H. Hutchinson、Wasyl Halczenko、Karen M. Brashear、Michael J. Breslin、Paul J. Coleman、Le T. Duong、Carmen Fernandez-Metzler、Michael A. Gentile、John E. Fisher、George D. Hartman、Joel R. Huff、Donald B. Kimmel、Chih-Tai Leu、Robert S. Meissner、Kara Merkle、Rose Nagy、Brenda Pennypacker、James J. Perkins、Thomayant Prueksaritanont、Gideon A. Rodan、Sandor L. Varga、Greg A. Wesolowski、Amy E. Zartman、Sevgi B. Rodan、Mark E. Duggan

  DOI：10.1021/jm030306r

  日期：2003.10.1

  3(S)-(6-Methoxypyridin-3-yl)-3-2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)propyl]-imidazolidin-1-yl}propionic acid 6 was identified as a potent and selective antagonist of the alpha(v)beta(3) receptor. This compound has an excellent in vitro profile (IC50 = 0.08 nM), a significant unbound fraction in human plasma (12%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in three in vivo models of bone turnover, the compound was selected for clinical development. To support the ongoing metabolism and safety studies, a novel strategy was employed in which a series of oxidized derivatives of 6 were prepared by exposure of 6 (or the methyl ester) to chemical oxidizing agents. These products proved useful in the identification of active metabolites generated by either in vitro or in vivo metabolism.