3(S)-(2-Methoxy-pyrimidin-5-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)-(2-Methoxy-pyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)-nonanoic acid
• 英文别名: (S)-3-(2-Methoxy-pyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid；(3S)-3-(2-methoxypyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid
• 化学式: C₂₂H₃₀N₄O₃
• 分子量: 398.505
• InChiKey: KKEMGRLKOQAUBU-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  97.2
• 氢给体数：
  2
• 氢受体数：
  7

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)-(2-Methoxy-pyrimidin-5-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

• [EN] INTEGRIN RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RECEPTEUR DE L'INTEGRINE
  申请人：MERCK & CO., INC.

  公开号：WO1999031061A1

  公开（公告）日：1999-06-24

  (EN) 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 $g(a)$g(n)$g(b)3, $g(a)$g(n)$g(b)5, and/or $g(a)$g(n)$g(b)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.(FR) L'invention concerne des composés et des dérivés desdits composés, leurs synthèses et leur utilisation comme antagonistes du récepteur de l'intégrine. Plus particulièrement, les composés de l'invention sont des antagonistes des récepteurs $g(a)$g(n)$g(b)3, $g(a)$g(n)$g(b)5 et/ou $g(a)$g(n)$g(b)6 de l'intégrine, et conviennent comme inhibiteurs de la résorption osseuse, produits de traitement ou de prévention de l'ostéoporose, de traitement des plaies, ou inhibiteurs de la resténose vasculaire, de la rétinopathie diabétique, de la dégénérescence maculaire, de l'angiogenèse, de l'athérosclérose, de l'inflammation, de maladies virales, de la croissance tumorale et de la métastase.

  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。更具体地说，本发明的化合物是整合素受体$g(a)$g(n)$g(b)3，$g(a)$g(n)$g(b)5和/或$g(a)$g(n)$g(b)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，肿瘤生长和转移。
• 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。
• 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. (a New Jersey corp.)

  公开号：EP1040098A1

  公开（公告）日：2000-10-04
• METHODS AND COMPOSITIONS FOR TREATING PERIODONTAL DISEASE
  申请人：Merck & Co., Inc.

  公开号：EP1349548A2

  公开（公告）日：2003-10-08