3(S)-(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)-(pyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)-nonanoic acid
• 英文别名: (S)-3-Pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid；(3S)-3-pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid
• 化学式: C₂₁H₂₈N₄O₂
• 分子量: 368.479
• InChiKey: DMDDFJFCCZFCKL-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  88
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3(S)-(pyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)-nonanoic acid 在 水 、 sodium hydroxide 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以95%的产率得到3(R)-(pyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)-(E)-non-4-enoic acid
  参考文献：
  名称：

  [EN] COMPOSITION AND METHODS FOR TREATING CHRONIC KIDNEY DISEASE
  [FR] COMPOSITION ET PROCÉDÉS DE TRAITEMENT DE MALADIE RÉNALE CHRONIQUE

  摘要：

  这项发明涉及利用RGD拟态整合素受体拮抗剂治疗慢性肾病，包括糖尿病肾病、局灶节段性肾小球硬化（FSGS）、肾病综合征、非糖尿病性慢性肾病、肾脏纤维化或急性肾损伤，可以作为单一药剂或与其他药剂联合使用。

  公开号：

  WO2016154369A1
• 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)-(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

• Alpha V integrin receptor antagonists
  申请人：——

  公开号：US20020040030A1

  公开（公告）日：2002-04-04

  The present invention relates to novel compounds formed by metabolic conversion of compounds of the structural formula depicted below (R═H or Me), pharmaceutical compositions containing such compounds, and their use as &agr;v&bgr;3 integrin receptor antagonists. The compounds of the present invention are useful for inhibiting bone resorption, restenosis, angiogenesis, diabetic retinopathy, macular degeneration, inflammatory arthritis, cancer, and metastatic tumor growth. They are particularly useful for inhibiting bone resorption and for the treatment and prevention of osteoporosis. 1

  本发明涉及通过代谢转化形成的新化合物，其结构式如下所示（R═H或Me），包含此类化合物的药物组合物，以及它们作为αvβ3整合素受体拮抗剂的用途。本发明的化合物对抑制骨吸收、再狭窄、血管生成、糖尿病视网膜病变、黄斑变性、炎症性关节炎、癌症和转移性肿瘤生长具有用处。它们特别适用于抑制骨吸收以及治疗和预防骨质疏松症。
• 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。
• Amine salt of an integrin receptor antagonist
  申请人：——

  公开号：US20030004171A1

  公开（公告）日：2003-01-02

  The tris(hydroxymethyl)aminomethane (“TRIS”) salt of 3-(pyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)-nonanoic acid is a potent antagonist of the integrin &agr;v&bgr;3 receptor and is useful for the prevention and/or treatment of osteoporosis and vascular restenosis, as well as conditions associated with excessive angiogenesis, such as macular degeneration, diabetic retinopathy, atherosclerosis, inflammatory arthritis, cancer, and metastatic tumor growth. The invention also relates to a process for the preparation of the novel salt as well as pharmaceutical compositions containing the salt and methods of using the salt.

  3-(嘧啶-5-基)-9-(5,6,7,8-四氢-[1,8]-萘啶-2-基)-壬酸的三(羟甲基)氨基甲烷（"TRIS"）盐是整合素&agr;v&bgr；3 受体的强效拮抗剂，可用于预防和/或治疗骨质疏松症和血管再狭窄，以及与过度血管生成有关的疾病，如黄斑变性、糖尿病视网膜病变、动脉粥样硬化、炎性关节炎、癌症和转移性肿瘤生长。本发明还涉及新型盐的制备过程以及含有该盐的药物组合物和使用该盐的方法。
• 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。