(S)-2-[(2E,4E)-5-methyl-2,4-hexadienoyl]-7-(2-{5-methyl-2-[(1E)-5-methylhex-1-en-1-yl]oxazol-4-yl}ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid tert-butylammonium salt | 1359767-78-4

• 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)-2-[(2E,4E)-5-methyl-2,4-hexadienoyl]-7-(2-{5-methyl-2-[(1E)-5-methylhex-1-en-1-yl]oxazol-4-yl}ethoxy)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid tert-butylammonium salt
• 英文别名: (3S)-2-[(2E)-5-methylhexa-2,4-dienoyl]-7-[2-[5-methyl-2-[(E)-5-methylhex-1-enyl]-1,3-oxazol-4-yl]ethoxy]-3,4-dihydro-1H-isoquinoline-3-carboxylic acid;2-methylpropan-2-amine
• CAS: 1359767-78-4
• 化学式: C₄H₁₁N*C₃₀H₃₈N₂O₅
• 分子量: 579.78
• InChiKey: HVDWSUSFZJNVOI-WIWNYAJDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.66
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  (E)-6-methyl-2-heptenoic acid 在 N-甲基吗啉 、 盐酸 、 4-二甲氨基吡啶 、 甲酸 、 二异丁基氢化铝 、 四乙基氟化铵水合物 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium hydroxide 、 三氯氧磷 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 异丙醇 、 甲苯 为溶剂， 反应 38.91h， 生成 (S)-2-[(2E,4E)-5-methyl-2,4-hexadienoyl]-7-(2-{5-methyl-2-[(1E)-5-methylhex-1-en-1-yl]oxazol-4-yl}ethoxy)-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.