N-benzyl-(R)-α-methylbenzyl-3(S)-(6-methoxypyridin-3-yl)-β-alanine ethyl ester | 227752-09-2

• 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: N-benzyl-(R)-α-methylbenzyl-3(S)-(6-methoxypyridin-3-yl)-β-alanine ethyl ester
• 英文别名: ethyl (3S)-3-[benzyl-[(1R)-1-phenylethyl]amino]-3-(6-methoxypyridin-3-yl)propanoate
• CAS: 227752-09-2
• 化学式: C₂₆H₃₀N₂O₃
• 分子量: 418.536
• InChiKey: BROJXPNJMURXTG-YKSBVNFPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  51.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-benzyl-(R)-α-methylbenzyl-3(S)-(6-methoxypyridin-3-yl)-β-alanine ethyl ester 在 palladium dihydroxide 盐酸 、 4-二甲氨基吡啶 、 sodium hydroxide 、 氢气 、 sodium acetate 、 sodium cyanoborohydride 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 、 乙酸乙酯 、 1,2-二氯乙烷 、 异丙醇 为溶剂， 反应 61.92h， 生成 (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 氢氧化钾 、 正丁基锂 、 溴 、 potassium bromide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 19.33h， 生成 N-benzyl-(R)-α-methylbenzyl-3(S)-(6-methoxypyridin-3-yl)-β-alanine 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

• [EN] INDAZOLE DERIVATIVES AS αV INTEGRIN ANTAGONISTS<br/>[FR] DÉRIVÉS D'INDAZOLE EN TANT QU'ANTAGONISTES DE L'INTÉGRINE αV
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2018089357A1

  公开（公告）日：2018-05-17

  The present invention provides compounds of Formula (Ia) or (Ib): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αV- containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αV-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

  本发明提供了式（Ia）或（Ib）的化合物：或其立体异构体、互变异构体或药学上可接受的盐或溶剂，其中所有变量如本文所定义。这些化合物是αV-含有整合素的拮抗剂。本发明还涉及包括这些化合物的药物组合物以及使用这些化合物和药物组合物治疗与αV-含有整合素失调相关的疾病、紊乱或状况的方法，如病理性纤维化、移植排斥、癌症、骨质疏松症和炎症性疾病。
• Non-peptide α v β 3 antagonists. Part 7: 3-Substituted tetrahydro- [1,8] naphthyridine derivatives
  作者：Jiabing Wang、Michael J. Breslin、Paul J. Coleman、Mark E. Duggan、Cecilia A. Hunt、John H. Hutchinson、Chih-Tai Leu、Sevgi B. Rodan、Gideon A. Rodan、Le T. Duong、George D. Hartman

  DOI：10.1016/j.bmcl.2003.11.036

  日期：2004.2

  A series of 3-substituted tetrahydro-[1,8]naphthyridine containing alpha(v)beta(3) antagonists was prepared. A comparison of their in vitro IC(50) values to the electron properties of the 3-substituents revealed a good linear Hammett correlation (rho=-1.96, R(2)=0.959). Electron-withdrawing groups at the 3-position of the tetrahydro-[1,8]naphthyridine decreased potency while electron-donating groups

  制备一系列含有α（v）β（3）拮抗剂的3-取代的四氢-[1,8]萘啶。它们的体外IC（50）值与3个取代基的电子性质的比较显示出良好的线性Hammett相关性（rho = -1.96，R（2）= 0.959）。在四氢-[1,8]萘啶的3位上的吸电子基团降低了效能，而供电子基团提高了效能。