ethyl (3S)-3-[benzyl-[(1R)-1-phenylethyl]amino]-3-(3-fluoro-4-methoxyphenyl)propanoate | 1026218-45-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl (3S)-3-[benzyl-[(1R)-1-phenylethyl]amino]-3-(3-fluoro-4-methoxyphenyl)propanoate
• CAS: 1026218-45-0
• 化学式: C₂₇H₃₀FNO₃
• 分子量: 435.539
• InChiKey: BNNATKWJKFKEMX-NLFFAJNJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl (3S)-3-[benzyl-[(1R)-1-phenylethyl]amino]-3-(3-fluoro-4-methoxyphenyl)propanoate 在 palladium dihydroxide 盐酸 、 氢气 、 sodium acetate 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 乙醇 、 乙酸乙酯 、 异丙醇 为溶剂， 生成 ethyl (3S)-3-(3-fluoro-4-methoxyphenyl)-3-[2-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propylamino]ethylamino]propanoate
  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-氟苯甲醚 在 氢氧化钾 、 正丁基锂 、 溴 、 palladium diacetate 、 三乙胺 、 三(邻甲基苯基)磷 、 potassium bromide 作用下， 以 四氢呋喃 、 正己烷 、 乙腈 为溶剂， 生成 ethyl (3S)-3-[benzyl-[(1R)-1-phenylethyl]amino]-3-(3-fluoro-4-methoxyphenyl)propanoate
  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

• Non-Peptide αvβ3 antagonists. Part 3: Identification of potent RGD mimetics incorporating novel β-Amino acids as aspartic acid replacements
  作者：Paul J Coleman、Karen M Brashear、Cecilia A Hunt、William F Hoffman、John H Hutchinson、Michael J Breslin、Carol A McVean、Ben C Askew、George D Hartman、Sevgi B Rodan、Gideon A Rodan、Chih-Tai Leu、Thomayant Prueksaritanont、Carmen Fernandez-Metzler、Bennett Ma、Laura A Libby、Kara M Merkle、Gary L Stump、Audrey A Wallace、Joseph J Lynch、Robert Lynch、Mark E Duggan

  DOI：10.1016/s0960-894x(01)00666-7

  日期：2002.1

  Potent non-peptidic alpha(v)beta(3) antagonists have been prepared incorporating various beta-amino acids as aspartic acid mimetics. Modification of the beta-alanine 3-substituents alters the potency and physicochemical properties of these receptor antagonists and in some cases provides orally bioavailable alpha(v)beta(3) inhibitors.

  强大的非肽α（v）β（3）拮抗剂已被制备，其中包含各种β-氨基酸作为天冬氨酸模拟物。β-丙氨酸3-取代基的修饰改变了这些受体拮抗剂的效力和理化性质，在某些情况下提供了口服生物利用的α（v）β（3）抑制剂。