Synthesis and Antiprotozoal Activity of Azabicyclo-Nonane Pyrimidine Hybrids

Abstract

2,4-Diaminopyrimidines and (dialkylamino)azabicyclo-nonanes possess activity against protozoan parasites. A series of fused hybrids were synthesized and tested in vitro against pathogens of malaria tropica and sleeping sickness. The activities and selectivities of compounds strongly depended on the substitution pattern of both ring systems as well as on the position of the nitrogen atom in the bicycles. The most promising hybrids of 3-azabicyclo-nonane with 2-aminopyrimidine showed activity against P. falciparum NF54 in submicromolar concentration and high selectivity. A hybrid with pyrrolidino substitution of the 2-azabicyclo-nonane as well as of the pyrimidine moiety exhibited promising activity against the multiresistant K1 strain of P. falciparum. A couple of hybrids of 2-azabicyclo-nonanes with 2-(dialkylamino)pyrimidines possessed high activity against Trypanosoma brucei rhodesiense STIB900 and good selectivity.

Molecular Docking, Synthesis, and Characterization of Furanyl‐Pyrazolyl Acetamide and 2,4‐Thiazolidinyl‐Furan‐3‐Carboxamide Derivatives as Neuroinflammatory Protective Agents

“…The findings demonstrated that doxorubicin displayed IC 50 values ranging from 1. 25 The cytotoxicity observation suggests that BV2 and HAPI cell lines possessed more cell viability in the presence of the test molecules compared with N9 and HMO6 cells and were selected for further investigation.…”

“…[4] Molecular hybrids are a promising area for research in medicinal chemistry as they incorporate different scaffolds into one molecule, improving their affinity and efficacy. [5][6][7] These hybrids have exhibited multifarious actions, including anticancer, [8][9][10][11][12][13][14][15][16][17] antimicrobial, [18,19] antiinflammatory, [20,21] anti-diabetic, [22][23][24] and antiprotozoal activities, [25][26][27] owing to their diverse pharmacophore characteristics. Molecular hybrids with furan, pyrazole, and thiazolidinedione moieties have recently gained significant attention.…”