Synthesis and antimicrobial evaluation of new 1,4-dihydro-4-pyrazolylpyridines and 4-pyrazolylpyridines

BACKGROUND: Dialkyl 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylates (1,4-DHP) have now been recognized as vital drugs. Some of these derivatives such as amlodipine, felodipine, isradipine, etc. have been commercialized. In view of wide range of biological properties associated with 1,4-DHP and owing to the biological importance of the oxidation step of 1,4-DHP, we carried out the synthesis and antimicrobial evaluation of new diethyl 1,4-dihydro-2,6-dimethyl-4-(3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (2a-g) and diethyl 2,6-dimethyl-4-(3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (3a-g). RESULTS: Synthesis of a series of new diethyl 1,4-dihydro-2,6-dimethyl-4-(3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (2a-g) has been accomplished by multicomponent cyclocondensation reaction of ethyl acetoacetate, 3-aryl-1-phenyl pyrazole-4-carboxaldehyde (1a-g) and ammonium acetate. The dihydropyridines 2a-g were smoothly converted to new diethyl 2,6-dimethyl-4-(3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (3a-g) using HTIB ([Hydroxy (tosyloxy)iodo]benzene, Koser's reagent) as the oxidizing agent. The antimicrobial studies of the title compounds, 2a-g &3a-g, are also described. GRAPHICAL ABSTRACT: Synthesis of a series of new diethyl 1,4-dihydro-2,6-dimethyl-4-(3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (2a-g), their aromatization using HTIB ([Hydroxy(tosyloxy)iodo]benzene, Koser's reagent) to afford new diethyl 2,6-dimethyl-4-(3-aryl-1-phenyl-4-pyrazolyl)pyridine-3,5-dicarboxylates (3a-g), and antimicrobial studies of 2a-g and 3a-g are reported.