Ayyiliath M. Sajith

Design, synthesis and structure--activity relationship (SAR) studies of imidazo[4,5-b]pyridine derived purine isosteres and their potential as cytotoxic agents.

Drug resistance to chemotherapeutic agents paved the way to develop novel synthetic molecules which are active on MDR cancer cell lines. Regio-isomeric imidazo[4,5-b]pyridine analogues were synthesized and evaluated for their cytotoxic activity against a range of cancer cell lines. The structure-activity relationship (SAR) studies of the imidazopyridine analogues are also described. Analogue 6b displayed strong cytotoxicity and good microsomal stability.

Cycloalkenyl nonaflates as electrophilic cross-coupling substrates for palladium catalyzed C–N bond forming reactions with enolizable heterocycles under microwave enhanced conditions

Microwave-mediated, palladium catalyzed C–N bond forming reactions with activated cycloalkenyl nonaflates and enolizable heterocycles using cesium carbonate as a base and a catalytic system employing Pd(OAc)2/Xantphos or Pd(OAc)2/dppp were found to be effective in driving the reactions to completion. This method resulted in good to excellent yields of the coupled products (22 examples, 25–90%) in short reaction time (30–60 min). Under optimum conditions, cycloalkenyl nonaflates were found to be an effective alternative to analogous triflates in C–N bond forming processes due to their increased stability under the reaction conditions. The use of tetrabutylammonium bromide (Bu4NBr) as an additive in these transformations proved to be effective and resulted in better yields of the coupled products.

Functionalised dihydroazo pyrimidine derivatives from Morita–Baylis–Hillman acetates: synthesis and studies against acetylcholinesterase as its inhibitors

A wide array of dihydro[1,5]azo[1,2-a]pyrimidine 2-esters have been synthesised at room temperature in moderate to good yields through one-pot reaction between nitrostyrene derived MBH acetates and aminoazole derivatives with γ-α cyclisation. The reaction involves a cascade SN2 reaction followed by intramolecular Michael addition–cyclisation with the generation of two new carbon–nitrogen bonds. The structure was further confirmed by single X-ray crystal analysis. Docking and in vitro studies of dihydrobenzimidazo pyrimidine derivatives against acetylcholinesterase (AChE) have been performed and the compounds 3d and 3e exhibit potent inhibitory activities with an IC50 of 46.8 nM and 42.5 nM respectively.

Mo(CO)6 as a Solid CO Source in the Synthesis of Aryl/Heteroaryl Weinreb Amides under Microwave-Enhanced Condition

The facile transformation of aryl/heteroaryl nonaflates into corresponding amides via Pd-catalyzed aminocarbonylation using Mo(CO)6 as a solid CO source under microwave-enhanced condition is reported. The method was found to be tolerant with respect to a diverse range of electronically biased aryl/heteroaryl nonaflates, and exceptional yields were obtained. The optimized protocol was further extended to a diverse range of amines.

Palladium-Catalyzed Suzuki Cross-Coupling of 2-Halo-Deazapurines with Potassium Organotrifluoroborate Salts in the Regioselective Synthesis of Imidazo[4,5-b]pyridine Analogues

In this paper, we report the use of potassium organotrifluoroborate salts as nucleophilic organoboron reagents in the Suzuki cross-coupling reactions of 2-halo deazapurines. Regio-isomeric C-2-substituted imidazo[4,5-b]pyridine analogues were synthesized by employing this protocol in good to excellent yields. Whereas aryl and heteroaryl trifluoroborates reacted readily to give the coupled products in high yields, alkyltrifluoroborates were found to be less reactive. The utilization of tetrabutylammonium acetate was found to play a substantial role in enhancing the reaction rates of the cross-coupling process. Also, a comparative study was performed between boronic acids and potassium organotrifluoroborate salts.