ABSTRACT
Combinatorial libraries of substituted 3-(methylthio)-5-(amino)-4-([1,2,4]oxadiazol-5-yl)-1H-pyrazoles 6, 10, 13, 15 (395 members, yields 32-87%), 4-([1,2,4]oxadiazol-5-yl)-1H-3,5-pyrazolediamines 8, 11 (571 members, yields 25-83%), 2-(methylthio)-3-([1,2,4]oxadiazol-5-yl)pyrazolo[1,5-a]pyrimidin-7(4H)-ones 17 (85 members, yields 56-95%), and 2-(amino)-3-([1,2,4]oxadiazol-5-yl)pyrazolo[1,5-a]pyrimidin-7(4H)-ones 18 (110 members, yields 56-95%) were synthesized by the parallel liquid-phase synthesis method.
Subject(s)
Combinatorial Chemistry Techniques/methods , Oxadiazoles/chemical synthesis , Small Molecule Libraries , Molecular Structure , Oxadiazoles/chemistry , Pyrazoles/chemistry , StereoisomerismABSTRACT
Several novel 2-imino-5-hydroxymethyl-8-methyl-2H-pyrano[2,3-c]pyridine-3-(N-aryl) carboxamides were prepared by reaction of pyridoxal hydrochloride with various N-arylcyanoacetamides. Reaction of these compounds with aromatic amines furnished a wide series of 2-(N-R-phenyl) imino-5-hydroxymethyl-8-methyl-2H-pyrano[2,3-c]pyridine-3-carboxamides. Antibacterial and antifungal activities of the synthesized compounds were studied. Most of the obtained compounds demonstrated significant activity against bacterial or fungal strains (MIC in the range of 12.5-25microg/mL), displaying comparable or even better efficacy than the standard drugs.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/pharmacology , Pyridines/pharmacology , Bacteria/drug effects , Candida albicans/drug effects , Ciprofloxacin/pharmacology , Fluconazole/pharmacology , Microbial Sensitivity Tests , Structure-Activity RelationshipABSTRACT
The parallel solution-phase synthesis of a new combinatorial library of 3-[4-(R1-coumarin-3-yl)-1,3-thiazol-2-ylcarbamoyl]propanoic acid amides 9 has been developed. The synthesis involves two steps: 1) the synthesis of core building blocks - 3- [4-(coumarin-3-yl)-1,3-thiazol-2-ylcarbamoyl]propanoic acids, 6 - by the reaction of 3-(omega-bromacetyl)coumarins 1 with 3-amino(thioxo)methylcarbamoylpropanoic acid (5); 2) the synthesis of the corresponding 3-[4-(coumarin-3-yl)-1,3-thiazol-2-yl- carbamoyl]propanoic acids amides 9 using 1,1'-carbonyldimidazole as a coupling reagent. The advantages of the method compared to existing ones are discussed.
