(S)-7-(2-{2-[(1E)-1-ethylprop-1-en-1-yl]-5-methyloxazol-4-yl}ethoxy)-2-[(2E,4E)-2,4-hexadienoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid tert-butylammonium salt | 1359767-56-8

• 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: (S)-7-(2-{2-[(1E)-1-ethylprop-1-en-1-yl]-5-methyloxazol-4-yl}ethoxy)-2-[(2E,4E)-2,4-hexadienoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid tert-butylammonium salt
• 英文别名: (3S)-2-[(2E,4E)-hexa-2,4-dienoyl]-7-[2-[5-methyl-2-[(E)-pent-2-en-3-yl]-1,3-oxazol-4-yl]ethoxy]-3,4-dihydro-1H-isoquinoline-3-carboxylic acid;2-methylpropan-2-amine
• CAS: 1359767-56-8
• 化学式: C₄H₁₁N*C₂₇H₃₂N₂O₅
• 分子量: 537.7
• InChiKey: RPSZQKFPURNXFI-MTIUZVMISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.63
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  methyl (S)-2-tert-butoxycarbonyl-7-{2-([(1E)-1-ethylprop-1-enyl]-5-methyloxazol-4-yl)ethoxy}-1,2,3,4-tetrahydroisoquinoline-3-carboxylate 在 盐酸 、 甲酸 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 异丙醇 为溶剂， 反应 2.5h， 生成 (S)-7-(2-{2-[(1E)-1-ethylprop-1-en-1-yl]-5-methyloxazol-4-yl}ethoxy)-2-[(2E,4E)-2,4-hexadienoyl]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid tert-butylammonium salt
  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

文献信息

• Novel (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids: Peroxisome proliferator-activated receptor γ selective agonists with protein-tyrosine phosphatase 1B inhibition
  作者：Kazuya Otake、Satoru Azukizawa、Masaki Fukui、Kazuyoshi Kunishiro、Hikaru Kamemoto、Mamoru Kanda、Tomohiro Miike、Masayasu Kasai、Hiroaki Shirahase

  DOI：10.1016/j.bmc.2011.11.035

  日期：2012.1

  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.