1-(2-Methyl-pyrimidin-5-yl)-7-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-hept-1-en-3-one | 312262-90-1

• 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: 1-(2-Methyl-pyrimidin-5-yl)-7-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-hept-1-en-3-one
• 英文别名: 1-(2-Methylpyrimidin-5-yl)-7-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-hept-1-en-3-one；(E)-1-(2-methylpyrimidin-5-yl)-7-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)hept-1-en-3-one
• CAS: 312262-90-1
• 化学式: C₂₀H₂₄N₄O
• 分子量: 336.437
• InChiKey: DWKDLCOMFBILNW-DHZHZOJOSA-N

物化性质

• 沸点：
  590.6±50.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  67.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2-Methyl-pyrimidin-5-yl)-7-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-hept-1-en-3-one 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.25h， 生成 (E,3R)-1-(2-methylpyrimidin-5-yl)-7-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)hept-1-en-3-ol
  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
• 作为产物：
  描述：

  6-氧代庚酸甲酯 在 正丁基锂 、 ammonium chloride 、 potassium carbonate 、 DL-脯氨酸 作用下， 以 四氢呋喃 、 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(2-Methyl-pyrimidin-5-yl)-7-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-hept-1-en-3-one
  参考文献：
  名称：

  &agr;v integrin receptor antagonists

  摘要：

  本发明涉及新颖的壬酸衍生物，它们的合成以及它们作为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，炎症，炎症性关节炎，病毒性疾病，癌症和转移性肿瘤生长。

  公开号：

  US06410526B1

文献信息

• Alpha v integrin receptor antagonists
  申请人：——

  公开号：US20040038963A1

  公开（公告）日：2004-02-26

  The present invention relates to novel chain-fluorinated alkanoic acid derivatives thereof, their synthesis, and their use as &agr;v integrin receptor antagonists. More particularly, the compounds of the present invention are antagonists of the integrin receptors &agr;v&bgr;3 and/or &agr;v&bgr;5 and are useful for inhibiting bone resorption, treating and preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammation, inflammatory arthritis, viral disease, cancer, and metastatic tumor growth.

  本发明涉及新型链氟化烷酸衍生物及其合成，以及其作为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/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，炎症，炎症性关节炎，病毒性疾病，癌症和转移性肿瘤生长。
• &agr;v integrin receptor antagonists
  申请人：Merck & Co., Inc.

  公开号：US06410526B1

  公开（公告）日：2002-06-25

  The present invention relates to novel nonanoic acid derivatives, their synthesis, and their use as &agr;v integrin receptor antagonists. More particularly, the compounds of the present invention are antagonists of the integrin receptors &agr;v&bgr;3 and &agr;v&bgr;5 and are useful for inhibiting bone resorption, treating and preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammation, inflammatory arthritis, viral disease, cancer, and metastatic tumor growth.

  本发明涉及新颖的壬酸衍生物，它们的合成以及它们作为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，炎症，炎症性关节炎，病毒性疾病，癌症和转移性肿瘤生长。
• 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。
• Process for preparation of integrin receptor antagonist intermediates
  申请人：——

  公开号：US20040030134A1

  公开（公告）日：2004-02-12

  A novel process is provided for the preparation of chiral intermediates useful in the asymmetric syntheses of &agr;v&bgr;3 integrin receptor antagonists. Also provided are the enantiomerically enriched intermediates that are obtained from the process.

  提供了一种新的工艺用于制备手性中间体，该中间体在αvβ3整合素受体拮抗剂的不对称合成中有用。还提供了从该工艺中获得的对映富集的中间体。
• Amine salts of an integrin receptor antagonist
  申请人：——

  公开号：US20020065291A1

  公开（公告）日：2002-05-30

  Amine salts of 3-(2-methyl-pyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)-nonanoic acid are potent antagonists of the integrin &agr;v&bgr;3 receptor and are 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 salts as well as pharmaceutical compositions containing the salts and methods of using the salts. Also disclosed are 3(R)- and 3(S)-(2-methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid in the form of a zwitterion trihydrate.

  3-(2-甲基嘧啶-5-基)-9-(5,6,7,8-四氢-[1,8]-萘啶-2-基)-壬酸的胺盐是整合素&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类的制备工艺以及含有这些盐类的药物组合物和使用这些盐类的方法。本发明还公开了3(R)-和3(S)-(2-甲基嘧啶-5-基)-9-(5,6,7,8-四氢-[1,8]萘啶-2-基)-壬酸的三水齐聚物形式。