2-butoxy-5-(3-(5-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-1,2,4-oxadiazol-5-yl)benzonitrile hydrochloride | 1286751-12-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-butoxy-5-(3-(5-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-1,2,4-oxadiazol-5-yl)benzonitrile hydrochloride
• 英文别名: 2-(butyloxy)-5-[3-(5-methyl-1,2,3,4-tetrahydro-6-isoquinolinyl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochloride
• CAS: 1286751-12-9
• 化学式: C₂₃H₂₄N₄O₂*ClH
• 分子量: 424.93
• InChiKey: SQPRJQAULNHJKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.83
• 重原子数：
  30.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  83.97
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-butoxy-5-(3-(5-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-1,2,4-oxadiazol-5-yl)benzonitrile hydrochloride 在 水 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium hydroxide 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 23.5h， 生成 sodium 3-[6-{5-[4-(butyloxy)-3-cyanophenyl]-1,2,4-oxadiazol-3-yl}-5-methyl-3,4-dihydro-2(1H)-isoquinolinyl]propanoate
  参考文献：
  名称：

  Discovery of a Selective S1P₁ Receptor Agonist Efficacious at Low Oral Dose and Devoid of Effects on Heart Rate

  摘要：

  Gilenya (fingolimod, FTY720) was recently approved by the U.S. FDA for the treatment of patients with remitting relapsing multiple sclerosis (RRMS). It is a potent agonist of four of the five sphingosine 1-phosphate (SIP) G-protein-coupled receptors (S1P(1) and S1P(3-5)). It has been postulated that fingolimod's efficacy is due to S1P(1) agonism, while its cardiovascular side effects (transient bradycardia and hypertension) are due to S1P(3) agonism. We have discovered a series of selective S1P(1), agonists, which includes 3-[6- (5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-5-methyl- 3,4-dihydro-2(1H)-isoquinolinyl]propanoate, 20, a potent, S1P(3)-sparing, orally active S1P(1) agonist. Compound 20 is as efficacious as fingolimod in a collagen-induced arthritis model and shows excellent pharmacokinetic properties preclinically. Importantly, the selectivity of 20 against S1P(3) is responsible for an absence of cardiovascular signal in telemetered rats, even at high dose levels.

  DOI：

  10.1021/ml2000214
• 作为产物：
  描述：

  6-羟基-5-甲基-3,4-二氢异喹啉-2(1h)-羧酸叔丁酯 在 吡啶 、 盐酸 、 四(三苯基膦)钯 、 盐酸羟胺 、 sodium hydride 、 碳酸氢钠 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 44.0h， 生成 2-butoxy-5-(3-(5-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)-1,2,4-oxadiazol-5-yl)benzonitrile hydrochloride
  参考文献：
  名称：

  Discovery of a Selective S1P₁ Receptor Agonist Efficacious at Low Oral Dose and Devoid of Effects on Heart Rate

  摘要：

  Gilenya (fingolimod, FTY720) was recently approved by the U.S. FDA for the treatment of patients with remitting relapsing multiple sclerosis (RRMS). It is a potent agonist of four of the five sphingosine 1-phosphate (SIP) G-protein-coupled receptors (S1P(1) and S1P(3-5)). It has been postulated that fingolimod's efficacy is due to S1P(1) agonism, while its cardiovascular side effects (transient bradycardia and hypertension) are due to S1P(3) agonism. We have discovered a series of selective S1P(1), agonists, which includes 3-[6- (5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-5-methyl- 3,4-dihydro-2(1H)-isoquinolinyl]propanoate, 20, a potent, S1P(3)-sparing, orally active S1P(1) agonist. Compound 20 is as efficacious as fingolimod in a collagen-induced arthritis model and shows excellent pharmacokinetic properties preclinically. Importantly, the selectivity of 20 against S1P(3) is responsible for an absence of cardiovascular signal in telemetered rats, even at high dose levels.

  DOI：

  10.1021/ml2000214