Synthesis and Structure鈥揂ctivity Relationship Studies in Translocator Protein Ligands Based on a Pyrazolo[3,4-b]quinoline Scaffold

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• 作者：Andrea Cappelli ; Giulia Bini ; Salvatore Valenti ; Germano Giuliani ; Marco Paolino ; Maurizio Anzini ; Salvatore Vomero ; Gianluca Giorgi ; Antonio Giordani ; Luigi Piero Stasi ; Francesco Makovec ; Carla Ghelardini ; Lorenzo Di Cesare Mannelli ; Alessandra Concas ; Patrizia Porcu ; Giovanni Biggio
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：October 27, 2011
• 年：2011
• 卷：54
• 期：20
• 页码：7165-7175
• 全文大小：1122K
• 年卷期：v.54,no.20(October 27, 2011)
• ISSN：1520-4804

文摘

As a further development of our large program focused on the medicinal chemistry of translocator protein [TSPO (18 kDa)] ligands, a new class of compounds related to alpidem has been designed using SSR180575, emapunil, and previously published pyrrolo[3,4-b]quinoline derivatives 9 as templates. The designed compounds were synthesized by alkylation of the easily accessible 4-methyl-2-phenyl-1H-pyrazolo[3,4-b]quinolin-3(2H)-one derivatives 13鈥?b>15 with the required bromoacetamides. Along with the expected 2-(4-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazolo[3,4-b]quinolin-1-yl)acetamide derivatives 10, 2-(4-methyl-3-oxo-2-phenyl-2H-pyrazolo[3,4-b]quinolin-9(3H)-yl)acetamide isomers 11 were isolated and characterized. The high TSPO affinity shown by new pyrazolo[3,4-b]quinoline derivatives 10 and especially 11 leads the way to further expand the chemical diversity in TSPO ligands and provides new templates and structure鈥揳ffinity relationship data potentially useful in the design of new anxiolytic and neuroprotective agents.