Design and Synthesis of Novel Pyrimidine/Hexahydroquinazoline‐Fused Pyrazolo[3,4‐ b ]Pyridine Derivatives, Their Biological Evaluation and Docking Studies #

Multicomponent reaction protocol has been developed for the synthesis of novel pyrimidine fused pyrazolo[3,4‐ b ]pyridine derivatives ( 7 a‐g ) and hexahydroquinazoline fused pyrazolo[3,4‐ b ] pyridine derivatives ( 8 a‐i ) starting from 3‐amino‐5‐carbethoxy‐6‐trifluoromethyl pyrazolo[3,4‐ b ] pyridine 5 . All the synthesized compounds were evaluated for antibacterial as well as antifungal activities and compounds 7 f, 8 a, 8 c and 8 d exhibited promising antibacterial activity. In particular, compound 2,4,6‐trifluoro substituted pyrimidine fused pyrazolo[3,4‐ b ]pyridine ( 7 f ) showed very good antibacterial activity against the panel of both Gram‐positive and ‐negative bacterial strains. Hexahydroquinazoline fused pyrazolo[3,4‐ b ]pyridine derivatives (8 f‐i) also showed promising antifungal activity and broad‐spectrum anti‐biofilm activity against both Gram‐positive and negative bacterial strains. The crystal structure of compound 8 b was solved based on single crystal X‐ray diffraction study. Docking studies were performed to identify the interactions of the compounds 7 f with crtM enzyme of Staphylococcus aureus .