(4aS,5R)-2-benzyl-5-[(1R,2S)-2-N-(benzyloxycarbonyl)amino-1-cyano-3-(indol-3-yl)-propyl]amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine | 251361-88-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4aS,5R)-2-benzyl-5-[(1R,2S)-2-N-(benzyloxycarbonyl)amino-1-cyano-3-(indol-3-yl)-propyl]amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine
• 英文别名: benzyl N-[(1R,2S)-1-[[(4aS,5R)-2-benzyl-1,3-dioxo-4,4a,5,6,7,8-hexahydropyrido[1,2-c]pyrimidin-5-yl]amino]-1-cyano-3-(1H-indol-3-yl)propan-2-yl]carbamate
• CAS: 251361-88-3
• 化学式: C₃₅H₃₆N₆O₄
• 分子量: 604.709
• InChiKey: JCHUBWCVTUOLIZ-ZLESDFJESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  45
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4aS,5R)-2-benzyl-5-[(1R,2S)-2-N-(benzyloxycarbonyl)amino-1-cyano-3-(indol-3-yl)-propyl]amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine 在 palladium on activated charcoal 盐酸 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、275.79 kPa 条件下， 反应 108.0h， 生成 (4aS,5R)-2-benzyl-5-[(4S,5R)-5-cyano-4-(indol-3-yl)methyl-2-oxoimidazolidin-1-yl]-1,3-dioxoperhydropyrido[1,2-c]pyrimidine
  参考文献：
  名称：

  5-(Tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-Based Potent and Selective CCK₁ Receptor Antagonists:  Structural Modifications at the Tryptophan Domain

  摘要：

  Analogues of the previously reported potent and highly selective CCK1 receptor antagonist (4aS,5R)-2-benzyl-5-(N-Boc-tryptophyl)amino-1,3-dioxoperhyropyrido-[1,2-c]pyrimidine (2a) were prepared to explore the structural requirements at the Boc-tryptophan domain for CCK1 receptor affinity. Structural modifications of 2a involved the Trp side chain, its conformational freedom, the Boc group, and the carboxamide bond. Results of the CCK binding and in vitro functional activity evaluation showed three highly strict structural requirements: the type and orientation of the Trp side chain, the H-bonding acceptor carbonyl group of the carboxamide bond, and the presence of the Trp amino protection Boc. Replacement of this acid-labile group with 3,3-dimethylbutyryl or tert-butylaminocarbonyl conferred acid stability to analogues 14a and 15a, which retained a high potency and selectivity in binding to CCK1 receptors, as well as an in vivo antagonist activity against the acute pancreatitis induced by caerulein in rats. Oral administration of compounds 14a and 15a also produced a lasting antagonism to the hypomotility induced by CCK-8 in mice, suggesting a good bioavailability and metabolic stability.

  DOI：

  10.1021/jm991078x
• 作为产物：
  描述：

  (4aR*,5S*)-2-benzyl-5-(tert-butoxycarbonyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine 在 三乙胺 、 三氟乙酸 、 zinc(II) chloride 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 17.0h， 生成 (4aS,5R)-2-benzyl-5-[(1R,2S)-2-N-(benzyloxycarbonyl)amino-1-cyano-3-(indol-3-yl)-propyl]amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine
  参考文献：
  名称：

  5-(Tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-Based Potent and Selective CCK₁ Receptor Antagonists:  Structural Modifications at the Tryptophan Domain

  摘要：

  Analogues of the previously reported potent and highly selective CCK1 receptor antagonist (4aS,5R)-2-benzyl-5-(N-Boc-tryptophyl)amino-1,3-dioxoperhyropyrido-[1,2-c]pyrimidine (2a) were prepared to explore the structural requirements at the Boc-tryptophan domain for CCK1 receptor affinity. Structural modifications of 2a involved the Trp side chain, its conformational freedom, the Boc group, and the carboxamide bond. Results of the CCK binding and in vitro functional activity evaluation showed three highly strict structural requirements: the type and orientation of the Trp side chain, the H-bonding acceptor carbonyl group of the carboxamide bond, and the presence of the Trp amino protection Boc. Replacement of this acid-labile group with 3,3-dimethylbutyryl or tert-butylaminocarbonyl conferred acid stability to analogues 14a and 15a, which retained a high potency and selectivity in binding to CCK1 receptors, as well as an in vivo antagonist activity against the acute pancreatitis induced by caerulein in rats. Oral administration of compounds 14a and 15a also produced a lasting antagonism to the hypomotility induced by CCK-8 in mice, suggesting a good bioavailability and metabolic stability.

  DOI：

  10.1021/jm991078x