methyl (S)-2-tert-butoxycarbonyl-7-(2-(5-methyl-2-[(1E)-5-methylhex-1-enyl]oxazol-4-yl)ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate | 1359767-33-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (S)-2-tert-butoxycarbonyl-7-(2-(5-methyl-2-[(1E)-5-methylhex-1-enyl]oxazol-4-yl)ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate
• CAS: 1359767-33-1
• 化学式: C₂₉H₄₀N₂O₆
• 分子量: 512.646
• InChiKey: GBGXSPHYNQNCSB-UKEJNIAMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.89
• 重原子数：
  37.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  91.1
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl (S)-2-tert-butoxycarbonyl-7-(2-(5-methyl-2-[(1E)-5-methylhex-1-enyl]oxazol-4-yl)ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate 在 盐酸 、 甲酸 、 三乙胺 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 0.5h， 生成 methyl (S)-2-[(2E,4E)-2,4-hexadienoyl]-7-(2-{5-methyl-2-[(1E)-5-methylhex-1-enyl]oxazol-4-yl}ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate
  参考文献：
  名称：

  Novel (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids: Peroxisome proliferator-activated receptor γ selective agonists with protein-tyrosine phosphatase 1B inhibition

  摘要：

  A novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and (S)-2-[(2E,4E)- hexadienoyl]-7-(2-(5-methyl-2-[( 1E)-5-methylhexen-1-yl]oxazol-4-yl]ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (14i) was identified as a potent human peroxisome proliferator-activated receptor gamma (PPAR gamma) selective agonist (EC(50) = 0.03 mu M) and human protein-tyrosine phosphatase 1B (PTP-1B) inhibitor (IC(50) = 1.18 mu M). C(max) after oral administration of 14i at 10 mg/kg was 2.2 mu g/ml (4.5 mu M) in male SD rats. Repeated administration of 14i and rosiglitazone for 14 days dose-dependently decreased plasma glucose levels, ED(50) = 4.3 and 23 mg/kg/day, respectively, in male KK-A(y) mice. In female SD rats, repeated administration of 14i at 12.5-100 mg/kg/day for 28 days had no effect on the hematocrit value (Ht) and red blood cell count (RBC), while rosiglitazone significantly decreased them from 25 mg/kg/day. In conclusion, 14i showed about a fivefold stronger hypoglycemic effect and fourfold or more weaker hemodilution effect than rosiglitazone, indicating that 14i is 20-fold or more safer than rosiglitazone. Compound 14i is a promising candidate for an efficacious and safe anti-diabetic drug targeting PPAR gamma and PTP-1B. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.035
• 作为产物：
  描述：

  在 四乙基氟化铵水合物 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 14.33h， 生成 methyl (S)-2-tert-butoxycarbonyl-7-(2-(5-methyl-2-[(1E)-5-methylhex-1-enyl]oxazol-4-yl)ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate
  参考文献：
  名称：

  Novel (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids: Peroxisome proliferator-activated receptor γ selective agonists with protein-tyrosine phosphatase 1B inhibition

  摘要：

  A novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and (S)-2-[(2E,4E)- hexadienoyl]-7-(2-(5-methyl-2-[( 1E)-5-methylhexen-1-yl]oxazol-4-yl]ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (14i) was identified as a potent human peroxisome proliferator-activated receptor gamma (PPAR gamma) selective agonist (EC(50) = 0.03 mu M) and human protein-tyrosine phosphatase 1B (PTP-1B) inhibitor (IC(50) = 1.18 mu M). C(max) after oral administration of 14i at 10 mg/kg was 2.2 mu g/ml (4.5 mu M) in male SD rats. Repeated administration of 14i and rosiglitazone for 14 days dose-dependently decreased plasma glucose levels, ED(50) = 4.3 and 23 mg/kg/day, respectively, in male KK-A(y) mice. In female SD rats, repeated administration of 14i at 12.5-100 mg/kg/day for 28 days had no effect on the hematocrit value (Ht) and red blood cell count (RBC), while rosiglitazone significantly decreased them from 25 mg/kg/day. In conclusion, 14i showed about a fivefold stronger hypoglycemic effect and fourfold or more weaker hemodilution effect than rosiglitazone, indicating that 14i is 20-fold or more safer than rosiglitazone. Compound 14i is a promising candidate for an efficacious and safe anti-diabetic drug targeting PPAR gamma and PTP-1B. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.035