3(S)-(6-Methoxy-pyridin-3-yl)-9-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)-nonanoic 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: 3(S)-(6-Methoxy-pyridin-3-yl)-9-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)-nonanoic acid
• 英文别名: (S)-3-(6-Methoxy-pyridin-3-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid；(3S)-3-(6-methoxypyridin-3-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid
• 化学式: C₂₃H₃₁N₃O₃
• 分子量: 397.517
• InChiKey: SQIDFFKYMURYAR-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  84.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-氧代庚酸甲酯 在 platinum(IV) oxide 、 palladium on activated charcoal sodium hydroxide 、 sodium tetrahydroborate 、 正丁基锂 、 1,4-环己二烯 、 氢气 、 potassium carbonate 、 丙酸 、 DL-脯氨酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 溶剂黄146 为溶剂， -78.0~145.0 ℃ 、101.33 kPa 条件下， 反应 81.58h， 生成 3(S)-(6-Methoxy-pyridin-3-yl)-9-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)-nonanoic acid
  参考文献：
  名称：

  Nonpeptide α_vβ₃ Antagonists. Part 11:  Discovery and Preclinical Evaluation of Potent α_vβ₃ Antagonists for the Prevention and Treatment of Osteoporosis

  摘要：

  3-(S)-Pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5e) and 3-(S)(methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5f) were identified as potent and selective antagonists of the alpha(v)beta(3) receptor. These compounds have excellent in vitro profiles (IC50 = 0.07 and 0.08 nM, respectively), significant unbound fractions in human plasma (6 and 4%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in an in vivo model of bone turnover following once-daily oral administration, these two compounds were selected for clinical development for the treatment of osteoporosis.

  DOI：

  10.1021/jm049874c

文献信息

• Integrin receptor antagonists
  申请人：——

  公开号：US20020010176A1

  公开（公告）日：2002-01-24

  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 &agr;v&bgr;3, &agr;v&bgr;5, and/or &agr;v&bgr;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, tumor growth, and metastasis.

  本发明涉及化合物及其衍生物，其合成以及它们作为整合素受体拮抗剂的用途。更具体地说，本发明的化合物是整合素受体αvβ3、αvβ5和/或αvβ6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，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。
• INTEGRIN RECEPTOR ANTAGONISTS
  申请人：Merck & Co., Inc. (a New Jersey corp.)

  公开号：EP1040098B1

  公开（公告）日：2005-04-27
• 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
• US6048861A
  申请人：——

  公开号：US6048861A

  公开（公告）日：2000-04-11