[2-oxo-6-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)hexyl]phosphonic acid dimethyl ester | 227752-03-6

• 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: [2-oxo-6-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)hexyl]phosphonic acid dimethyl ester
• 英文别名: Dimethyl (2-oxo-6-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)hexyl)phosphonate；1-dimethoxyphosphoryl-6-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)hexan-2-one
• CAS: 227752-03-6
• 化学式: C₁₆H₂₅N₂O₄P
• 分子量: 340.359
• InChiKey: KJMXMUWEGVNEFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [2-oxo-6-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)hexyl]phosphonic acid dimethyl ester 在 palladium on activated charcoal sodium hydroxide 、 sodium tetrahydroborate 、 1,4-环己二烯 、 potassium carbonate 、 丙酸 作用下， 以 四氢呋喃 、 甲醇 、 溶剂黄146 为溶剂， 反应 20.25h， 生成 (S)-3-(2-Isopropyl-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
• 作为产物：
  描述：

  6-氧代庚酸甲酯 在 正丁基锂 、 ammonium chloride 、 DL-脯氨酸 作用下， 以 四氢呋喃 、 乙醇 、 乙酸乙酯 为溶剂， 生成 [2-oxo-6-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)hexyl]phosphonic acid dimethyl ester
  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

• [EN] COMPOSITION AND METHODS FOR TREATING CHRONIC KIDNEY DISEASE<br/>[FR] COMPOSITION ET PROCÉDÉS DE TRAITEMENT DE MALADIE RÉNALE CHRONIQUE
  申请人：MERCK SHARP & DOHME

  公开号：WO2016154369A1

  公开（公告）日：2016-09-29

  This invention relates to the treatment of chronic kidney disease, including diabetic nephropathy, focal segmental glomerulosclerosis (FSGS), nephrotic syndrome, non-diabetic chronic kidney disease, renal fibrosis or acute kidney injury by the administration of an RGD mimetic integrin receptor antagonist, either as a single agent or in combination with other agents.

  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。
• 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。
• 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。
• 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下述结构式化合物（R＆boxH;H或Me）形成的新化合物，含有这种化合物的制药组合物，以及它们作为&agr;v&bgr;3整合素受体拮抗剂的用途。本发明的化合物对于抑制骨吸收、再狭窄、血管生成、糖尿病视网膜病变、黄斑变性、炎性关节炎、癌症和转移性肿瘤生长非常有用。它们特别适用于抑制骨吸收以及治疗和预防骨质疏松症。
• FLUORINATED TETRAHYDRONAPHTHYRIDINYL NONANOIC ACID DERIVATIVES AND USES THEREOF
  申请人：SciFluor Life Sciences, Inc.

  公开号：US20160244447A1

  公开（公告）日：2016-08-25

  The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating fibrosis, macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof.

  本发明涉及式I的氟化合物及其合成方法。本发明还涉及包含本发明中的氟化合物的制药组合物，以及通过将这些化合物和制药组合物用于需要治疗纤维化、黄斑退化、糖尿病视网膜病变（DR）、黄斑水肿、糖尿病性黄斑水肿（DME）和视网膜静脉阻塞后的黄斑水肿（RVO）的患者来进行治疗的方法。