Synthesis and Antiproliferative Activity of Some Newly Synthesized Pyrazolopyridine Derivatives

Abstract

A series of pyrazolopyridine derivatives is synthesized from emyl-4-amino-6-memyl-1-(mphtha[1,2-d]-[1,3]tmazol-2-yl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (3), and the products are tested for their anti-proliferative activity. Treatment of compound 3 with sodium hydroxide and following reaction with acetic anhydride gives 2-amino-5-methyl-7-(naphtho[1,2-d]thiazol-2-yl)pyrazolo[4′,3′:5,6]pyrido[4,3-d][1,3]oxazin-4 (7H)-one (5). Compound 3 reacts with phenyl isothiocyanate to afford thiourea derivative 6, which upon treatment with KOH gives 3-phenyl-5-methyl -7-(naphtho[1,2-d][1,3]thiazol-2-yl)-2-thioxo-1,2,3,7-tetrahydro-4H-pyrazolo[4′,3′:5,6]pyrido[4,3-d]pyrimidin-4-one (7). Upon reaction of compound 3 with benzoyl isothiocyanate the benzoyl thiourea derivative 8 is formed. Its cyclization with an alkali leads to 5-methyl-7-(naphtha[1,2-d]thiazol-2-yl)-2-thioxo-1,2,3,7-tetrahydro-4H-pyrazolo-[4′,3′:5,6]pyrido[4,3-d]pyrimidin-4-one (9). Reaction of compound 3 with hydrazine gives 4-amino-6-methyl-1-(naphtho[1,2-d][1,3]thiazol-2-yl)-1H-pyrazolo[3,4-b]pyridine-5-carbohydrazide (10), reaction of which with formaldehyde gives 3-amino-5-methyl-7-(naphtho[1,2-d][1,3]thiazol-2-yl)-1,2,3,7-tetrahydro-4H-pyrazolo[4′,3′:5,6]pyrido[4,3-d]pyrimidin-4-one (11). More reactions of compound 3 are presented. Some synthesized pyrazolopyridine derivatives are tested as anti-proliferative agents. The detailed synthesis, spectroscopic data, and anti-proliferative activity are reported.