Synthesis and antiviral activity of new 4-(phenylamino)/4-[(methylpyridin-2-yl)amino]-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acids derivatives

The synthesis of new 4-( phenylamino)-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (3a-l) derivatives and the new 4-[(methylpyridin-2-yl) amino]-1-phenyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (5a-c) derivatives was achieved with an efficient synthetic route. Ethyl 4-chloro-1-phenyl-1H-pyrazolo[ 3,4-b]pyridine-5-carboxylate ( 1) on fusion with appropriate substituted anilines or aminopicolines gave the required new ethyl-4-(phenylamino)-1-phenyl-1H- pyrazolo[3,4-b]pyridine-5-carboxylates (2a-l) ( 52-82%) or new ethyl 4[(methylpyridin-2-yl) amino]-1-phenyl-1H- pyrazolo[3,4-b]pyridine-5-carboxylates (4a-c) ( 50-60%), respectively. Subsequent hydrolysis of the esters afforded the corresponding carboxylic acids (3a-l) ( 86-93%) and (5a-c) in high yield (80-93%). Inhibitory effects of 4-( phenylamino)/4-[(methylpyridin-2-yl) amino]-1-phenyl-1Hpyrazolo[3,4-b]pyridine-4-carboxylic acids. Derivatives on Herpes simplex virus type 1 (HSV-1), Mayaro virus ( MAY) and vesicular stomatitis virus (VSV) were investigated. Compounds 2d, 3f, 3a, and 3c exhibited antiviral activity against HSV-1, MAY, and VSV virus with EC50 values of 6.8, 2.2, 4.8, 0.52, 2.5, and 1.0. None of these compounds showed toxicity for Vero cells.