ethyl 4-(((S)-1-phenylethyl)amino)pentanoate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 4-(((S)-1-phenylethyl)amino)pentanoate
• 英文别名: ethyl 4-[[(1S)-1-phenylethyl]amino]pentanoate
• 化学式: C₁₅H₂₃NO₂
• 分子量: 249.353
• InChiKey: XBVZCWRUGZEJTH-ABLWVSNPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 4-(((S)-1-phenylethyl)amino)pentanoate 在 四氯化碳 、 palladium on carbon 、 potassium tert-butylate 、 甲酸铵 、 sodium ethanolate 、 三乙酰氧基硼氢化钠 、 sodium hydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 、 甲苯 、 乙腈 、 mineral oil 为溶剂， 反应 35.5h， 生成 5-((S)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid [5-(1-methylcyclopropyl)-2H-pyrazol-3-yl]amide
  参考文献：
  名称：

  Discovery of Oral VEGFR-2 Inhibitors with Prolonged Ocular Retention That Are Efficacious in Models of Wet Age-Related Macular Degeneration

  摘要：

  The benefit of intravitreal anti-VEGF therapy in treating wet age-related macular degeneration (AMD) is well established. Identification of VEGFR-2 inhibitors with optimal ADME properties for an ocular indication provides opportunities for dosing routes beyond intravitreal injection. We employed a high throughput in vivo screening strategy with rodent models of choroidal neovascularization and iterative compound design to identify VEGFR-2 inhibitors with potential to benefit wet AMD patients. These compounds demonstrate preferential ocular tissue distribution and efficacy after oral administration while minimizing systemic exposure.

  DOI：

  10.1021/acs.jmedchem.5b01227
• 作为产物：
  描述：

  (S)-(-)- α-甲基苄胺 、 乙酰丙酸乙酯 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 16.0h， 生成 ethyl 4-(((S)-1-phenylethyl)amino)pentanoate
  参考文献：
  名称：

  Discovery of Oral VEGFR-2 Inhibitors with Prolonged Ocular Retention That Are Efficacious in Models of Wet Age-Related Macular Degeneration

  摘要：

  The benefit of intravitreal anti-VEGF therapy in treating wet age-related macular degeneration (AMD) is well established. Identification of VEGFR-2 inhibitors with optimal ADME properties for an ocular indication provides opportunities for dosing routes beyond intravitreal injection. We employed a high throughput in vivo screening strategy with rodent models of choroidal neovascularization and iterative compound design to identify VEGFR-2 inhibitors with potential to benefit wet AMD patients. These compounds demonstrate preferential ocular tissue distribution and efficacy after oral administration while minimizing systemic exposure.

  DOI：

  10.1021/acs.jmedchem.5b01227

文献信息

• Discovery of Oral VEGFR-2 Inhibitors with Prolonged Ocular Retention That Are Efficacious in Models of Wet Age-Related Macular Degeneration
  作者：Erik L. Meredith、Nello Mainolfi、Stephen Poor、Yubin Qiu、Karl Miranda、James Powers、Donglei Liu、Fupeng Ma、Catherine Solovay、Chang Rao、Leland Johnson、Nan Ji、Gerald Artman、Leo Hardegger、Shawn Hanks、Siyuan Shen、Amber Woolfenden、Elizabeth Fassbender、Jeremy M. Sivak、Yiqin Zhang、Debby Long、Rosemarie Cepeda、Fang Liu、Vinayak P. Hosagrahara、Wendy Lee、Peter Tarsa、Karen Anderson、Jason Elliott、Bruce Jaffee

  DOI：10.1021/acs.jmedchem.5b01227

  日期：2015.12.10

  The benefit of intravitreal anti-VEGF therapy in treating wet age-related macular degeneration (AMD) is well established. Identification of VEGFR-2 inhibitors with optimal ADME properties for an ocular indication provides opportunities for dosing routes beyond intravitreal injection. We employed a high throughput in vivo screening strategy with rodent models of choroidal neovascularization and iterative compound design to identify VEGFR-2 inhibitors with potential to benefit wet AMD patients. These compounds demonstrate preferential ocular tissue distribution and efficacy after oral administration while minimizing systemic exposure.