7-(2-benzyloxy-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-(2,3-dihydrobenzo[b]furan-6-yl)-5-hydroxy-5H-cyclopenta[b]pyridine | 721965-55-5

• 分子结构分类: 有机化合物
• 英文名称: 7-(2-benzyloxy-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-(2,3-dihydrobenzo[b]furan-6-yl)-5-hydroxy-5H-cyclopenta[b]pyridine
• CAS: 721965-55-5
• 化学式: C₃₅H₃₃NO₆
• 分子量: 563.65
• InChiKey: RWICFVHCOFIWFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.0
• 重原子数：
  42.0
• 可旋转键数：
  7.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  87.11
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  7-(2-benzyloxy-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-(2,3-dihydrobenzo[b]furan-6-yl)-5-hydroxy-5H-cyclopenta[b]pyridine 在 palladium dihydroxide 4-二甲氨基吡啶 、 氢气 、 碳酸氢钠 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 46.0h， 生成 (5RS,6RS,7SR)-7-(2-hydroxy-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-(2,3-dihydrobenzo[b]furan-6-yl)-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
• 作为产物：
  描述：

  6-溴-2,3-二氢-1-苯并呋喃 、 7-(2-benzyloxy-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-oxocyclopenta-1,3-dieno[2,1-b]pyridine 在 magnesium 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以89%的产率得到7-(2-benzyloxy-4-methoxyphenyl)-6-tert-butoxycarbonyl-5-(2,3-dihydrobenzo[b]furan-6-yl)-5-hydroxy-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