A Parallel Synthesis Demonstration Library of Tri-Substituted Indazoles Containing New Antimutagenic / Antioxidant Hits Related to Benzydamine
| Autor: | Lester A. Mitscher, Hemin Vaidya, Segaran P. Pillai, Sanjay R. Menon, Ramdas Vidya |
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| Rok vydání: | 2003 |
| Předmět: |
chemistry.chemical_classification
Spectrometry Mass Electrospray Ionization Indazole Indazoles Magnetic Resonance Spectroscopy Aryl Organic Chemistry Antimutagenic Agents General Medicine Alkylation Combinatorial chemistry Antioxidants Computer Science Applications Acylation chemistry.chemical_compound chemistry Nucleophilic aromatic substitution Yield (chemistry) Reagent Drug Discovery Combinatorial Chemistry Techniques Organic chemistry Alkyl |
| Zdroj: | Combinatorial Chemistry & High Throughput Screening. 6:471-480 |
| ISSN: | 1386-2073 |
| DOI: | 10.2174/138620703106298644 |
| Popis: | A solution phase strategy for the multiple parallel synthesis of a demonstration library of indazoles is described by which regio-selectivity problems inherent to previous syntheses of this nucleus are largely overcome. Synthesis of selected components proceeded satisfactorily indicating that a fully realized library of indazole analogs could readily be produced using this methodology. Simple modifications of the basic nucleophilic aromatic substitution route unambiguously produce a range of N-1 substitutions (alkyl, aryl and aralkyl) in 50-75% yields. Next a range of substituents was introduced at the C-3 position in 50-80% yields by O-alkylation. Careful choice of reagents and reaction conditions were required to prevent by-product formation due to competing alkylation at N-2 (trace to 15% yields). When present, these contaminants were readily removed by chromofiltration. A third diversity site was sketched in at C-5 in 75-90% yield by reductive alkylation or acylation. Screening of some of the demonstration library members in vitro revealed highly active antioxidants suggesting that producing a full library would be worthwhile. |
| Databáze: | OpenAIRE |
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