(4aS,5R)-2-benzyl-5-[N-(tert-butoxycarbonyl)-L-tryptophyl]amino-1-oxoperhydropyrido[1,2-c]pyrimidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (4aS,5R)-2-benzyl-5-[N-(tert-butoxycarbonyl)-L-tryptophyl]amino-1-oxoperhydropyrido[1,2-c]pyrimidine
• 英文别名: tert-butyl N-[(2S)-1-[[(4aS,5R)-2-benzyl-1-oxo-4,4a,5,6,7,8-hexahydro-3H-pyrido[1,2-c]pyrimidin-5-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamate
• 化学式: C₃₁H₃₉N₅O₄
• 分子量: 545.682
• InChiKey: IMWMUTIUKLDZRB-PVHODMMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-叔丁氧羰基-L-色氨酸 在 sodium tetrahydroborate 、 TEA 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 nickel dichloride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 30.25h， 生成 (4aS,5R)-2-benzyl-5-[N-(tert-butoxycarbonyl)-L-tryptophyl]amino-1-oxoperhydropyrido[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:  Structure−Activity Relationship Studies on the Central 1,3-Dioxoperhydropyrido[1,2-c]pyrimidine Scaffold

  摘要：

  To further define the pharmacophore of the potent and selective 5-(tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based CCK1 receptor antagonists the electronic and topographic properties of the central 1, 3-dioxoperhydro-pyrido[1,2-c]pyrimidine scaffold have been modified. With this aim, the 1- and 3-oxo groups have been replaced by the thioxo- and deoxi-analogues, and the fused piperidine ring has been contracted to the corresponding pyrrolidine moiety. The results of the evaluation of the new analogues as CCK receptor ligands, in rat pancreas and cerebral cortex preparations, showed that, whereas replacement of oxygen with sulfur is allowed, reduction of the 1- or 3-oxo groups or the contraction of the fused piperidine ring lead to the complete loss of binding affinity at CCK1 receptors. The thioxo-analogues 5a, 8a, 12a, and 12b showed functional CCK1 antagonist activity, inhibiting the CCK-8-stimulated amylase release from pancreatic acinar cells. The 1-thioxo analogue 5a, with subnanomolar affinity (IC50 = 0.09 x 10(-9) M), was found to be the most potent and selective compound within the family of 5-(tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based CCK1 antagonists.

  DOI：

  10.1021/jm010898i

文献信息

• 5-(Tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-<i>c</i>]pyrimidine-Based Potent and Selective CCK₁ Receptor Antagonists:  Structure−Activity Relationship Studies on the Central 1,3-Dioxoperhydropyrido[1,2-<i>c</i>]pyrimidine Scaffold
  作者：José M. Bartolomé-Nebreda、M. Teresa García-López、Rosario González-Muñiz、Edurne Cenarruzabeitia、Miriam Latorre、Joaquín Del Río、Rosario Herranz

  DOI：10.1021/jm010898i

  日期：2001.11.1

  To further define the pharmacophore of the potent and selective 5-(tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based CCK1 receptor antagonists the electronic and topographic properties of the central 1, 3-dioxoperhydro-pyrido[1,2-c]pyrimidine scaffold have been modified. With this aim, the 1- and 3-oxo groups have been replaced by the thioxo- and deoxi-analogues, and the fused piperidine ring has been contracted to the corresponding pyrrolidine moiety. The results of the evaluation of the new analogues as CCK receptor ligands, in rat pancreas and cerebral cortex preparations, showed that, whereas replacement of oxygen with sulfur is allowed, reduction of the 1- or 3-oxo groups or the contraction of the fused piperidine ring lead to the complete loss of binding affinity at CCK1 receptors. The thioxo-analogues 5a, 8a, 12a, and 12b showed functional CCK1 antagonist activity, inhibiting the CCK-8-stimulated amylase release from pancreatic acinar cells. The 1-thioxo analogue 5a, with subnanomolar affinity (IC50 = 0.09 x 10(-9) M), was found to be the most potent and selective compound within the family of 5-(tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based CCK1 antagonists.