(5S,6R,7R)-(+)-7-(2-acetoxymethyl-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-(2,3-dihydrobenzo[b]furan-6-yl)-2-(N-benzoyl-isopropylamino)-6,7-dihydro-5H-cyclopenta[b]pyridine | 721965-60-2

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (5S,6R,7R)-(+)-7-(2-acetoxymethyl-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-(2,3-dihydrobenzo[b]furan-6-yl)-2-(N-benzoyl-isopropylamino)-6,7-dihydro-5H-cyclopenta[b]pyridine
• CAS: 721965-60-2
• 化学式: C₄₁H₄₄N₂O₇
• 分子量: 676.81
• InChiKey: PBFIFOYRFWWYRH-AGSXMJPOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.38
• 重原子数：
  50.0
• 可旋转键数：
  9.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  104.26
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (5S,6R,7R)-(+)-7-(2-acetoxymethyl-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-(2,3-dihydrobenzo[b]furan-6-yl)-2-(N-benzoyl-isopropylamino)-6,7-dihydro-5H-cyclopenta[b]pyridine 在 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 2.0h， 以91%的产率得到tert-butyl (5S,6R,7R)-(+)-5-(2,3-dihydrobenzo[b]furan-6-yl)-7-(2-hydroxymethyl-4-methoxyphenyl)-2-(N-isopropylamino)-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate
  参考文献：
  名称：

  Potent and orally active ETA selective antagonists with 5,7-diarylcyclopenteno[1,2-b]pyridine-6-carboxylic acid structures

  摘要：

  The synthesis and structure-activity relationships of a series of 5,7-diarylcyclopenteno[1,2-b]pyridine-6-carboxylic acids are described. Our efforts have been focused on modification of the aryl ring at the 5-position and the alkyl substituent at the 2-position of the bottom 4-methoxyphenyl ring in an effort to develop orally available ETA selective antagonists with safer profiles in terms of the P-450 enzyme inhibitory activity. Incorporation of a hydroxymethyl group as an alkyl substituent in methylenedioxyphenyl and 6-dihydrobenzofuran derivatives led to the identification of orally bioavailable ETA selective antagonists 1f and 7f. These compounds also showed not only excellent binding affinity (IC50 < 0.10 nM, more than 800-fold selectivity for the ETA receptor over the ETB receptor) but also sufficient oral bioavailability, 481% and 56%, respectively, in rats. Furthermore, these compounds did not exhibit either competitive or mechanism-based inhibition of human cytochrome P450 enzymes. (c) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.033
• 作为产物：
  描述：

  5-溴-2,2-二氟-1,3-苯并二噁唑 在 palladium dihydroxide 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium tetrahydroborate 、 potassium tert-butylate 、 氢气 、 碳酸氢钠 、 magnesium 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， -78.0~130.0 ℃ 、101.33 kPa 条件下， 反应 0.33h， 生成 (5S,6R,7R)-(+)-7-(2-acetoxymethyl-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-(2,3-dihydrobenzo[b]furan-6-yl)-2-(N-benzoyl-isopropylamino)-6,7-dihydro-5H-cyclopenta[b]pyridine
  参考文献：
  名称：

  Potent and orally active ETA selective antagonists with 5,7-diarylcyclopenteno[1,2-b]pyridine-6-carboxylic acid structures

  摘要：

  The synthesis and structure-activity relationships of a series of 5,7-diarylcyclopenteno[1,2-b]pyridine-6-carboxylic acids are described. Our efforts have been focused on modification of the aryl ring at the 5-position and the alkyl substituent at the 2-position of the bottom 4-methoxyphenyl ring in an effort to develop orally available ETA selective antagonists with safer profiles in terms of the P-450 enzyme inhibitory activity. Incorporation of a hydroxymethyl group as an alkyl substituent in methylenedioxyphenyl and 6-dihydrobenzofuran derivatives led to the identification of orally bioavailable ETA selective antagonists 1f and 7f. These compounds also showed not only excellent binding affinity (IC50 < 0.10 nM, more than 800-fold selectivity for the ETA receptor over the ETB receptor) but also sufficient oral bioavailability, 481% and 56%, respectively, in rats. Furthermore, these compounds did not exhibit either competitive or mechanism-based inhibition of human cytochrome P450 enzymes. (c) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.033