3(S)-(6-methoxypyridin-3-yl)-3-{2-[3-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)propylamino]ethylamino}propionic acid ethyl ester | 227963-55-5

• 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: 3(S)-(6-methoxypyridin-3-yl)-3-{2-[3-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)propylamino]ethylamino}propionic acid ethyl ester
• 英文别名: 3(S)-(6-Methoxypyridin-3-yl)-3-{2-[3-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-propylamino]-ethylamino}-propionic Acid Ethyl Ester；ethyl (3S)-3-(6-methoxypyridin-3-yl)-3-[2-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propylamino]ethylamino]propanoate
• CAS: 227963-55-5
• 化学式: C₂₄H₃₅N₅O₃
• 分子量: 441.574
• InChiKey: NFPFCXRBLZDECF-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  32
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  97.4
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3(S)-(6-methoxypyridin-3-yl)-3-{2-[3-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)propylamino]ethylamino}propionic acid ethyl ester 在 4-二甲氨基吡啶 、 sodium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 20.0h， 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 palladium dihydroxide 盐酸 、 氢氧化钾 、 正丁基锂 、 氢气 、 溴 、 sodium acetate 、 sodium cyanoborohydride 、 溶剂黄146 、 potassium bromide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 乙酸乙酯 、 异丙醇 为溶剂， 反应 61.25h， 生成 3(S)-(6-methoxypyridin-3-yl)-3-{2-[3-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)propylamino]ethylamino}propionic acid 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

• Alpha v integrin receptor antagonists
  申请人：——

  公开号：US20040192670A1

  公开（公告）日：2004-09-30

  The present invention relates to cyclic urea derivatives, their synthesis, and their use as &agr;v integrinreceptor antagonists. More particularly, the compounds of the present invention are antagonists of the integrin receptors &agr;v&bgr;3 and &agr;v&bgr;15 and are useful for inhibiting bone resorption, treating and preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammatory arthritis, tumor growth and metastasis.

  本发明涉及环脲衍生物、其合成以及作为αv整合素受体拮抗剂的用途。更具体地说，本发明的化合物是αvβ3和αvβ15整合素受体的拮抗剂，可用于抑制骨吸收、治疗和预防骨质疏松症，抑制血管再狭窄、糖尿病视网膜病变、黄斑变性、血管生成、动脉粥样硬化、炎症性关节炎、肿瘤生长和转移。
• αν integrin receptor antagonists
  申请人：Hutchinson John H.

  公开号：US06916810B2

  公开（公告）日：2005-07-12

  The present invention relates to cyclic urea derivatives, their synthesis, and their use as αv integrinreceptor antagonists. More particularly, the compounds of the present invention are antagonists of the integrin receptors αvβ3 and/or αvβ5 and are useful for inhibiting bone resorption, treating and preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammatory arthritis, tumor growth and metastasis.

  本发明涉及环状脲衍生物，其合成以及其作为αv整合素受体拮抗剂的用途。更具体地，本发明的化合物是αvβ3和/或αvβ5整合素受体的拮抗剂，可用于抑制骨吸收，治疗和预防骨质疏松症，抑制血管再狭窄，糖尿病视网膜病变，黄斑变性，血管生成，动脉粥样硬化，炎性关节炎，肿瘤生长和转移。
• INTEGRIN RECEPTOR ANTAGONISTS
  申请人：MERCK & CO., INC.

  公开号：EP1040111B1

  公开（公告）日：2005-06-22
• US6017926A
  申请人：——

  公开号：US6017926A

  公开（公告）日：2000-01-25
• US6916810B2
  申请人：——

  公开号：US6916810B2

  公开（公告）日：2005-07-12