（硫代）乙内酰脲与含2-芳基乙胺骨架的四氢异喹啉和四氢-β-咔啉的溶液相平行环化反应。

Solution-phase parallel annulation of (thio)hydantoins to tetrahydroisoquinolines and tetrahydro-beta-carbolines containing the 2-arylethyl amine scaffold.

作者信息

Blanco-Ania Daniel, Hermkens Pedro H H, Sliedregt Leo A J M, Scheeren Hans W, Rutjes Floris P J T

机构信息

Institute for Molecules and Materials, Radboud University Nijmegen, Toernooiveld 1, Nijmegen, The Netherlands.

出版信息

J Comb Chem. 2009 Jul-Aug;11(4):547-55. doi: 10.1021/cc8001926.

DOI:10.1021/cc8001926

PMID:19472984

Abstract

The one-step solution-phase parallel synthesis of two structurally diverse libraries of pharmacologically important compounds is described. The presented compounds combine three privileged structures: the 2-arylethyl amine moiety, a tetrahydro(hetero)areno[c]pyridine, and a (thio)hydantoin. These compounds are synthesized by annulation of a hydantoin or a 2-thiohydantoin ring to tri- or tetracyclic scaffolds, containing the 2-arylethyl amine moiety and a tetrahydroisoquinoline, a tetrahydro-beta-carboline, or a tetrahydrofuro[3,2-c]pyridine. The annulation leads to pharmacologically relevant structural motifs such as imidazopyrroloisoquinolines, dioxoloimidazopyrroloisoquinolines, furoimidazopyrrolopyridines, and imidazopyrrolopyridoindoles. Both libraries were obtained with quantitative yields. The 36-membered hydantoin library was obtained with purities from 57 to 100% (90% average) and the 32-membered thiohydantoin library with purities from 73 to 100% (94% average).

摘要

本文描述了一步溶液相平行合成两个结构多样的具有药理学重要性的化合物库。所呈现的化合物结合了三种优势结构：2-芳基乙胺部分、四氢（杂）芳并[c]吡啶和（硫）乙内酰脲。这些化合物是通过将乙内酰脲或2-硫代乙内酰脲环环合到含有2-芳基乙胺部分和四氢异喹啉、四氢-β-咔啉或四氢呋喃并[3,2-c]吡啶的三环或四环支架上合成的。环合产生了药理学相关的结构基序，如咪唑并吡咯并异喹啉、二氧杂环咪唑并吡咯并异喹啉、呋喃咪唑并吡咯吡啶和咪唑并吡咯吡啶并吲哚。两个库均以定量产率获得。36元乙内酰脲库的纯度为57%至100%（平均90%），32元硫代乙内酰脲库的纯度为73%至100%（平均94%）。