3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine | 748814-08-6

• 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: 3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine
• CAS: 748814-08-6
• 化学式: C₁₂H₁₉N₃
• 分子量: 205.303
• InChiKey: FDRUABYFTPEWDP-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  50.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine 在 palladium dihydroxide 硫酸 、 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 40.0 ℃ 、482.63 kPa 条件下， 生成 (S)-3-(6-Methoxy-pyridin-3-yl)-3-{3-[3-((R)-7-methyl-5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-propyl]-2-oxo-imidazolidin-1-yl}-propionic acid
  参考文献：
  名称：

  Nonpeptide αvβ3 antagonists. Part 10: In vitro and in vivo evaluation of a potent 7-methyl substituted tetrahydro-[1,8]naphthyridine derivative

  摘要：

  Subtle modifications were incorporated into the structure of clinical candidate 1. These changes were designed to maintain potency and selectivity while inducing changes in physical properties leading to improved pharmacokinetics in three species. This approach led to the identification of 4 as a potent, selective alpha(v)beta(3) receptor antagonist that was selected for clinical development based on an improved PK profile and efficacy demonstrated in an in vivo model of bone turnover. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.06.040
• 作为产物：
  描述：

  2-(5-溴吡啶-2-基)-丙-2-炔-1-醇 在 palladium on activated charcoal bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 偶氮二甲酸二异丙酯 、 氢气 、 potassium carbonate 、 一水合肼 、 sodium amide 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 20.0~90.0 ℃ 、275.79 kPa 条件下， 反应 59.0h， 生成 3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine
  参考文献：
  名称：

  Methods for the Synthesis of 5,6,7,8-Tetrahydro-1,8-naphthyridine Fragments for α_Vβ₃ Integrin Antagonists

  摘要：

  The preparation of 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine 2a and 3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine 2b, key intermediates in the synthesis of alpha(V)beta(3) antagonists, is described. The syntheses rely on the efficient double Sonogashira reactions of 2,5-dibromopyridine 3 with acetylenic alcohols 4a/4b and protected propargylamines 10a-e followed by Chichibabin cyclizations of 3,3'-pyridine-2,5-diyldipropan-1-amines 9a/9b.

  DOI：

  10.1021/jo0486950

文献信息

• Methods for the Synthesis of 5,6,7,8-Tetrahydro-1,8-naphthyridine Fragments for α_Vβ₃ Integrin Antagonists
  作者：Frederick W. Hartner、Yi Hsiao、Kan K. Eng、Nelo R. Rivera、Michael Palucki、Lushi Tan、Nobuyoshi Yasuda、David L. Hughes、Steven Weissman、Daniel Zewge、Tony King、Dave Tschaen、R. P. Volante

  DOI：10.1021/jo0486950

  日期：2004.12.1

  The preparation of 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine 2a and 3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine 2b, key intermediates in the synthesis of alpha(V)beta(3) antagonists, is described. The syntheses rely on the efficient double Sonogashira reactions of 2,5-dibromopyridine 3 with acetylenic alcohols 4a/4b and protected propargylamines 10a-e followed by Chichibabin cyclizations of 3,3'-pyridine-2,5-diyldipropan-1-amines 9a/9b.
• Nonpeptide αvβ3 antagonists. Part 10: In vitro and in vivo evaluation of a potent 7-methyl substituted tetrahydro-[1,8]naphthyridine derivative
  作者：Michael J Breslin、Mark E Duggan、Wasyl Halczenko、George D Hartman、Le T Duong、Carmen Fernandez-Metzler、Michael A Gentile、Donald B Kimmel、Chih-Tai Leu、Kara Merkle、Thomayant Prueksaritanont、Gideon A Rodan、Sevgi B Rodan、John H Hutchinson

  DOI：10.1016/j.bmcl.2004.06.040

  日期：2004.9

  Subtle modifications were incorporated into the structure of clinical candidate 1. These changes were designed to maintain potency and selectivity while inducing changes in physical properties leading to improved pharmacokinetics in three species. This approach led to the identification of 4 as a potent, selective alpha(v)beta(3) receptor antagonist that was selected for clinical development based on an improved PK profile and efficacy demonstrated in an in vivo model of bone turnover. (C) 2004 Elsevier Ltd. All rights reserved.