(S)-3-(2,3-dihydrobenzofuran-6-yl)-3-(2-oxo-3-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)imidazolidin-1-yl)propanoic acid

• 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: (S)-3-(2,3-dihydrobenzofuran-6-yl)-3-(2-oxo-3-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)imidazolidin-1-yl)propanoic acid
• 英文别名: 3(S)-(2,3-dihydro-benzofuran-6-yl)-3-{2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)-propyl]-imidazolidin-1-yl}-propionic acid；3(S)-(2,3-Dihydro-benzofuran-6-yl)-3-{2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-propyl]-imidazolidin-1-yl}-propionic acid；(S)-3-(2,3-Dihydro-benzofuran-6-yl)-3-{2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-propyl]-imidazolidin-1-yl}-propionic acid；(3S)-3-(2,3-dihydro-1-benzofuran-6-yl)-3-[2-oxo-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]imidazolidin-1-yl]propanoic acid
• 化学式: C₂₅H₃₀N₄O₄
• 分子量: 450.538
• InChiKey: WURWJPCCHUZQHY-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  95
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,3-二氢苯并呋喃 在 palladium dihydroxide 盐酸 、 4-二甲氨基吡啶 、 氢氧化钾 、 sodium hydroxide 、 正丁基锂 、 氢气 、 溴 、 sodium acetate 、 palladium diacetate 、 sodium cyanoborohydride 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 三(邻甲基苯基)磷 、 potassium bromide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 乙酸乙酯 、 1,2-二氯乙烷 、 异丙醇 、 乙腈 为溶剂， 生成 (S)-3-(2,3-dihydrobenzofuran-6-yl)-3-(2-oxo-3-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)imidazolidin-1-yl)propanoic 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

文献信息

• Integrin receptor antagonists
  申请人：Merck & Co., Inc.

  公开号：US06017926A1

  公开（公告）日：2000-01-25

  The present invention relates to compounds and derivatives thereof, their synthesis, and their use as integrin receptor antagonists. More particularly, the compounds of the present invention are antagonists of the integrin receptors .alpha.v.beta.3, .alpha.v.beta.5 and/or .alpha.v.beta.6 and are useful for inhibiting bone resorption, treating and preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammation, wound healing, viral disease, and tumor growth and metastasis.

  本发明涉及化合物及其衍生物，它们的合成以及它们作为整合素受体拮抗剂的用途。更具体地，本发明的化合物是整合素受体α.v.β.3、α.v.β.5和/或α.v.β.6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、伤口愈合、病毒性疾病以及肿瘤生长和转移。
• Treatment of inflammation with a combination of a cyclooxygenase-2 inhibitor and an integrin alpha-v antagonist
  申请人：——

  公开号：US20020040039A1

  公开（公告）日：2002-04-04

  The present invention provides for methods for treating or preventing an inflammatory disease or condition in a mammalian patient in need of such treatment comprising administering to said patient a cyclooxygenase-2 specific inhibitor in combination with an &agr; V &bgr; 3 , &agr; V &bgr; 5 and/or &agr; V &bgr; 6 integrin receptor antagonist in an amount effective to treat or prevent the inflammatory disease or condition. The present invention also provides for pharmaceutical compositions for the treatment or prevention of an inflammatory disease or condition. Further, the invention provides for the manufacture of a medicament useful in the treatment or prevention of an inflammatory disease or condition.

  本发明提供了在需要治疗的哺乳动物患者中治疗或预防炎症性疾病或病症的方法，包括给所述患者施用环氧化酶-2 特异性抑制剂，该抑制剂与 &agr； V &bgr； 3 , &agr； V &bgr； 5 和/或 &agr； V &bgr； 6 整合素受体拮抗剂，其用量对治疗或预防炎症性疾病或病症有效。本发明还提供了用于治疗或预防炎症性疾病或病症的药物组合物。此外，本发明还提供了一种用于治疗或预防炎症性疾病或病症的药物的制造方法。
• Methods and compositions for treating peridontal disease
  申请人：——

  公开号：US20040053968A1

  公开（公告）日：2004-03-18

  The present invention provides for a method for the treatment of alveolar bone loss due to periodontal disease in a subject in need of such treatment comprising administration of a therapeutically effective amount of an &agr;v&bgr;3 integrin receptor antagonist in combination with a therapeutically effective amount of a COX-2 inhibitor. Further, the present invention provides for pharmaceutical compositions useful in the methods of the present invention, as well as a method of manufacture of a medicament useful for treating the alveolar bone loss due to periodontal disease.

  本发明提供了一种治疗需要这种治疗的受试者因牙周病引起的牙槽骨缺损的方法，该方法包括施用治疗有效量的&agr;v&bgr;3整合素受体拮抗剂与治疗有效量的COX-2抑制剂。此外，本发明还提供了在本发明方法中有用的药物组合物，以及一种用于治疗牙周病引起的牙槽骨丧失的药物的制造方法。
• INTEGRIN RECEPTOR ANTAGONISTS
  申请人：MERCK & CO., INC.

  公开号：EP1040111A1

  公开（公告）日：2000-10-04
• TREATMENT OF INFLAMMATION WITH A COMBINATION OF A CYCLOOXYGENASE-2 INHIBITOR AND AN INTEGRIN ALPHA-V ANTAGONIST
  申请人：Merck & Co., Inc.

  公开号：EP1322311A1

  公开（公告）日：2003-07-02