3-pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)nonanoic acid ethyl ester | 227752-22-9

• 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-pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)nonanoic acid ethyl ester
• CAS: 227752-22-9
• 化学式: C₂₃H₃₂N₄O₂
• 分子量: 396.533
• InChiKey: DOQVOLZWWCHFFG-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.46
• 重原子数：
  29.0
• 可旋转键数：
  11.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  77.0
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  3-pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)nonanoic acid ethyl ester 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 16.0h， 以69%的产率得到3(S)-(pyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)-nonanoic acid
  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
• 作为产物：
  描述：

  嘧啶-5-甲醛 在 palladium on activated charcoal sodium tetrahydroborate 、 1,4-环己二烯 、 potassium carbonate 、 丙酸 作用下， 以 四氢呋喃 、 甲醇 、 溶剂黄146 为溶剂， 反应 4.25h， 生成 3-pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)nonanoic acid ethyl ester
  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