[2-[3-(1H-benzoimidazol-2-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-1-(4-tert-butoxybenzyl)-2-oxo-ethyl]carbamic acid tert-butyl ester | 781662-43-9

• 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: [2-[3-(1H-benzoimidazol-2-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-1-(4-tert-butoxybenzyl)-2-oxo-ethyl]carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2S)-1-[3-(1H-benzimidazol-2-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-3-[4-[(2-methylpropan-2-yl)oxy]phenyl]-1-oxopropan-2-yl]carbamate
• CAS: 781662-43-9
• 化学式: C₃₄H₄₀N₄O₄
• 分子量: 568.716
• InChiKey: UUGVSKNVRQVORZ-XLTVJXRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  96.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  三氟乙酸 、 [2-[3-(1H-benzoimidazol-2-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-1-(4-tert-butoxybenzyl)-2-oxo-ethyl]carbamic acid tert-butyl ester 生成 (2S)-2-amino-1-[(3R)-3-(1H-benzoimidazol-2-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-3-(4-hydroxyphenyl)propan-1-one bis-trifluoroacetate 、 (2S)-2-amino-1-[(3S)-3-(1H-benzoimidazol-2-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-3-(4-hydroxyphenyl)propan-1-one bis-trifluoroacetate
  参考文献：
  名称：

  Rationale, Design, and Synthesis of Novel Phenyl Imidazoles as Opioid Receptor Agonists for Gastrointestinal Disorders

  摘要：

  A small series of novel, imidazoles 4 have been prepared that exhibit very good binding affinities for the delta and mu opioid receptors (ORs), as well as demonstrate potent agonist functional activity at the delta OR. Representative imidazole 4a (K-i delta = 0.9 nM; K-i mu = 55 nM; K-i kappa = 124 nM; EC50 delta = 13-25 nM) was further profiled for OR related in vivo effects. Compound 4a reduced gastrointestinal (GI) propulsive motility in a dose-dependent and naloxone-reversible manner, based on the results of the mouse glass bead expulsion test (3, 5, and 10 mg/kg, ip) and the mouse fecal pellet output test (1 and 3 mg/kg, ip). Compound 4a showed no analgesic activity as measured by the mouse abdominal irritant test (MAIT) when dosed at 100 mg/kg, sc, but did show significant MAIT activity at doses of both 10 mug (40% inhibition) and 100 mug (100% inhibition) when dosed intracerebroventricularly (icv). Taken together, these in vivo results suggest that 4a acts peripherally when dosed systemically, and that these prototypical compounds may prove promising as medicinal leads for GI indications.

  DOI：

  10.1021/jm030548r
• 作为产物：
  描述：

  3,4-二氢一异喹啉-2,3-二甲酸-2-苄酯 在 N-甲基吗啉 、 碘代三甲硅烷 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 氯甲酸异丁酯 作用下， 以 二氯甲烷 、 氯仿 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.5h， 生成 [2-[3-(1H-benzoimidazol-2-yl)-3,4-dihydro-1H-isoquinolin-2-yl]-1-(4-tert-butoxybenzyl)-2-oxo-ethyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  Rationale, Design, and Synthesis of Novel Phenyl Imidazoles as Opioid Receptor Agonists for Gastrointestinal Disorders

  摘要：

  A small series of novel, imidazoles 4 have been prepared that exhibit very good binding affinities for the delta and mu opioid receptors (ORs), as well as demonstrate potent agonist functional activity at the delta OR. Representative imidazole 4a (K-i delta = 0.9 nM; K-i mu = 55 nM; K-i kappa = 124 nM; EC50 delta = 13-25 nM) was further profiled for OR related in vivo effects. Compound 4a reduced gastrointestinal (GI) propulsive motility in a dose-dependent and naloxone-reversible manner, based on the results of the mouse glass bead expulsion test (3, 5, and 10 mg/kg, ip) and the mouse fecal pellet output test (1 and 3 mg/kg, ip). Compound 4a showed no analgesic activity as measured by the mouse abdominal irritant test (MAIT) when dosed at 100 mg/kg, sc, but did show significant MAIT activity at doses of both 10 mug (40% inhibition) and 100 mug (100% inhibition) when dosed intracerebroventricularly (icv). Taken together, these in vivo results suggest that 4a acts peripherally when dosed systemically, and that these prototypical compounds may prove promising as medicinal leads for GI indications.

  DOI：

  10.1021/jm030548r