(S)-1-pyrimidin-5-yl-7-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)hept-1-en-3-ol

• 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: (S)-1-pyrimidin-5-yl-7-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)hept-1-en-3-ol
• 英文别名: (E,3S)-1-pyrimidin-5-yl-7-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)hept-1-en-3-ol
• 化学式: C₁₉H₂₄N₄O
• 分子量: 324.426
• InChiKey: KOMMVFSEWJXOET-HKMNZKMDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  70.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-氧代庚酸甲酯 在 platinum(IV) oxide sodium tetrahydroborate 、 正丁基锂 、 氢气 、 potassium carbonate 、 DL-脯氨酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 为溶剂， -78.0 ℃ 、101.33 kPa 条件下， 反应 62.58h， 生成 (S)-1-pyrimidin-5-yl-7-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)hept-1-en-3-ol
  参考文献：
  名称：

  Nonpeptide α_vβ₃ Antagonists. Part 11:  Discovery and Preclinical Evaluation of Potent α_vβ₃ Antagonists for the Prevention and Treatment of Osteoporosis

  摘要：

  3-(S)-Pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5e) and 3-(S)(methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5f) were identified as potent and selective antagonists of the alpha(v)beta(3) receptor. These compounds have excellent in vitro profiles (IC50 = 0.07 and 0.08 nM, respectively), significant unbound fractions in human plasma (6 and 4%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in an in vivo model of bone turnover following once-daily oral administration, these two compounds were selected for clinical development for the treatment of osteoporosis.

  DOI：

  10.1021/jm049874c

文献信息

• Nonpeptide α_vβ₃ Antagonists. Part 11:  Discovery and Preclinical Evaluation of Potent α_vβ₃ Antagonists for the Prevention and Treatment of Osteoporosis
  作者：Paul J. Coleman、Karen M. Brashear、Ben C. Askew、John H. Hutchinson、Carol A. McVean、Le T. Duong、Bradley P. Feuston、Carmen Fernandez-Metzler、Michael A. Gentile、George D. Hartman、Donald B. Kimmel、Chih-Tai Leu、Lorraine Lipfert、Kara Merkle、Brenda Pennypacker、Thomayant Prueksaritanont、Gideon A. Rodan、Gregg A. Wesolowski、Sevgi B. Rodan、Mark E. Duggan

  DOI：10.1021/jm049874c

  日期：2004.9.1

  3-(S)-Pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5e) and 3-(S)(methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5f) were identified as potent and selective antagonists of the alpha(v)beta(3) receptor. These compounds have excellent in vitro profiles (IC50 = 0.07 and 0.08 nM, respectively), significant unbound fractions in human plasma (6 and 4%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in an in vivo model of bone turnover following once-daily oral administration, these two compounds were selected for clinical development for the treatment of osteoporosis.