Rodriguez Loaiza Pilar, Löber Stefan, Hübner Harald, Gmeiner Peter
Department of Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany.
Bioorg Med Chem. 2007 Dec 1;15(23):7248-57. doi: 10.1016/j.bmc.2007.08.038. Epub 2007 Aug 25.
'Click resins' enable solid phase supported reactions to work under nearly perfect conditions fulfilling the requirements of click chemistry. Utilizing the formylpyrrolylmethyltriazole (FPMT) linker 6, which is readily available via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), a BAL strategy could be successfully applied for a parallel synthesis of dopaminergic phenylacetylens. A focused library of 20 test compounds revealing three points of diversity was generated by a four-step SPOS approach including microwave assisted Sonogashira coupling. GPCR-ligand binding assays indicated excellent dopamine D3 and D4 receptor binding affinities which were identified to cause a partial agonist activity for the most potent test compounds 2c,e,i,k.
“点击树脂”使固相支持反应能够在近乎完美的条件下进行，满足点击化学的要求。利用通过铜（I）催化的叠氮化物-炔烃环加成反应（CuAAC）容易获得的甲酰基吡咯基甲基三唑（FPMT）连接体6，一种BAL策略能够成功应用于多巴胺能苯乙炔的平行合成。通过包括微波辅助的Sonogashira偶联的四步固相合成方法，生成了一个包含20种测试化合物的聚焦文库，该文库揭示了三个多样性点。GPCR配体结合试验表明，对于最有效的测试化合物2c、e、i、k，具有优异的多巴胺D3和D4受体结合亲和力，这些化合物被鉴定为具有部分激动剂活性。
