1-pyrimidin-5-yl-7-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)hept-1-en-3-one | 593282-77-0

• 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-pyrimidin-5-yl-7-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)hept-1-en-3-one
• 英文别名: (E)-1-pyrimidin-5-yl-7-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)hept-1-en-3-one
• CAS: 593282-77-0
• 化学式: C₁₉H₂₂N₄O
• 分子量: 322.41
• InChiKey: DJIYBDYNTFVDTM-JXMROGBWSA-N

物化性质

• 沸点：
  598.7±50.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 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-pyrimidin-5-yl-7-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)hept-1-en-3-one 在 palladium on activated charcoal sodium tetrahydroborate 、 1,4-环己二烯 、 丙酸 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 反应 3.25h， 生成 3-pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)nonanoic acid ethyl ester
  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 platinum(IV) oxide 正丁基锂 、 氢气 、 potassium carbonate 、 DL-脯氨酸 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 为溶剂， -78.0 ℃ 、101.33 kPa 条件下， 反应 62.33h， 生成 1-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：

  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] 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。
• 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。
• Compositions Methods for Treating Chronic Kidney Disease
  申请人：COX Jason M.

  公开号：US20180110762A1

  公开（公告）日：2018-04-26

  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.
• Composition and Methods for Treating Chronic Kidney Disease
  申请人：MERCK SHARP & DOHME CORP

  公开号：US20190307735A1

  公开（公告）日：2019-10-10

  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.
• US6764842B2
  申请人：——

  公开号：US6764842B2

  公开（公告）日：2004-07-20