(RS)-3-([1,1'-biphenyl]-4-yl)-3-(5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanamido)propanoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (RS)-3-([1,1'-biphenyl]-4-yl)-3-(5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanamido)propanoic acid
• 英文别名: 3-(4-Phenylphenyl)-3-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]propanoic acid；3-(4-phenylphenyl)-3-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]propanoic acid
• 化学式: C₂₈H₃₁N₃O₃
• 分子量: 457.572
• InChiKey: ANHVXOMSUJRVTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  91.3
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-氨基-3-(4-联苯基)丙酸 在 N-甲基吗啉 、 氯化亚砜 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 40.0h， 生成 (RS)-3-([1,1'-biphenyl]-4-yl)-3-(5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanamido)propanoic acid
  参考文献：
  名称：

  Structure Activity Relationships of α_v Integrin Antagonists for Pulmonary Fibrosis by Variation in Aryl Substituents

  摘要：

  Antagonism of alpha(v)beta(6) is emerging as a potential treatment of idiopathic pulmonary fibrosis based on strong target validation. Starting from an alpha(v)beta(3) antagonist lead and through simple variation in the nature and position of the aryl substituent, the discovery of compounds with improved alpha(v)beta(6) activity is described. The compounds also have physicochemical properties commensurate with oral bioavailability and are high quality starting points for a drug discovery program. Compounds 33S and 43E1 are pan av antagonists having ca. 100 nM potency against alpha(v)beta(3), alpha(v)beta(5), alpha(v)beta(6), and av beta 8 in cell adhesion assays. Detailed structure activity relationships with these integrins are described which also reveal substituents providing partial selectivity (defined as at least a 0.7 log difference in pIC(50) values between the integrins in question) for alpha(v)beta(3) and alpha(v)beta(5).

  DOI：

  10.1021/ml5002079

文献信息

• Structure Activity Relationships of α_v Integrin Antagonists for Pulmonary Fibrosis by Variation in Aryl Substituents
  作者：James Adams、Edward C. Anderson、Emma E. Blackham、Yin Wa Ryan Chiu、Thomas Clarke、Natasha Eccles、Luke A. Gill、Joshua J. Haye、Harvey T. Haywood、Christian R. Hoenig、Marius Kausas、Joelle Le、Hannah L. Russell、Christopher Smedley、William J. Tipping、Tom Tongue、Charlotte C. Wood、Jason Yeung、James E. Rowedder、M. Jonathan Fray、Thomas McInally、Simon J. F. Macdonald

  DOI：10.1021/ml5002079

  日期：2014.11.13

  Antagonism of alpha(v)beta(6) is emerging as a potential treatment of idiopathic pulmonary fibrosis based on strong target validation. Starting from an alpha(v)beta(3) antagonist lead and through simple variation in the nature and position of the aryl substituent, the discovery of compounds with improved alpha(v)beta(6) activity is described. The compounds also have physicochemical properties commensurate with oral bioavailability and are high quality starting points for a drug discovery program. Compounds 33S and 43E1 are pan av antagonists having ca. 100 nM potency against alpha(v)beta(3), alpha(v)beta(5), alpha(v)beta(6), and av beta 8 in cell adhesion assays. Detailed structure activity relationships with these integrins are described which also reveal substituents providing partial selectivity (defined as at least a 0.7 log difference in pIC(50) values between the integrins in question) for alpha(v)beta(3) and alpha(v)beta(5).