发明名称 |
SOLID PHASE AND COMBINATORIAL SYNTHESIS OF SUBSTITUTED THIOPHENES AND OF ARRAYS OF SUBSTITUTED THIOPHENES |
摘要 |
A solid phase method for the synthesis of a plurality of differently substituted thiophenes with a wide variety of side-chain substituents as compounds of potential therapeutic interest. The thiophenes are prepared by acylation of a substrate-bound primary or secondary amine with cyanoacetic acid and reaction of the resulting cyanoacetamide with an isothiocyanate in the presence of a base. Alkylation with an appropriate alkyl halide, followed by Thorpe-Ziegler-cyclization yields differently substituted, support-bound 3-aminothiophenes. These may be screened on the substrate or cleaved from the substrate and then screened in solution. Alternatively, the resin-bound 3-aminothiophenes or the synthetic intermediates can be subjected to further synthetic transformations (N-acylation, reduction) on the support, which permits the preparation of further therapeutically interesting compounds. The efficient synthesis of a wide variety of thiophenes using automated synthesis technology of the present method makes these compounds attractive candidates for the generation and rapid screening of diverse thiophene-based libraries. The method disclosed provides an easy and fact access to highly diverse heterocyclic compounds of therapeutic interest, amenable to automatization.
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申请公布号 |
WO9740034(A1) |
申请公布日期 |
1997.10.30 |
申请号 |
WO1997DK00180 |
申请日期 |
1997.04.22 |
申请人 |
NOVO NORDISK A/S;DOEWWALD, FLORENCIO, ZARAGOZA |
发明人 |
DOEWWALD, FLORENCIO, ZARAGOZA |
分类号 |
C07D333/36;A61K31/495;A61K31/496;C07D333/38;(IPC1-7):C07D333/36;A61K31/38 |
主分类号 |
C07D333/36 |
代理机构 |
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