RESUMO
A series of 2-[(2,6)-dimethylphenyl]benzimidazole analogs displayed strong potential for mutagenicity following metabolic activation in either TA98 or TA100 Salmonella typhimurium strains. The number of revertants was significantly reduced by replacing the 2,6-dimethylphenyl group with a 2,6-dichlorophenyl moiety. Time-dependent CYP3A4 inhibition was also observed with a compound containing a 2-[(2,6)-dimethylphenyl] benzimidazole ring, implying risk for this scaffold to generate reactive metabolites.
Assuntos
Anti-Helmínticos/farmacologia , Benzimidazóis/farmacologia , Inibidores do Citocromo P-450 CYP3A , Mutagênicos/farmacologia , Salmonella typhimurium/efeitos dos fármacos , Albendazol/farmacologia , Citocromo P-450 CYP3A , Testes de Mutagenicidade , Salmonella typhimurium/genética , Fatores de TempoRESUMO
The chemoselective functionalization of 5-bromo-2-chloro-3-fluoropyridine (1c) is described. Catalytic amination conditions (Pd2dba3, Xantphos, base) afford exclusively the bromide substitution product (2) for both secondary amines and primary anilines. A reversal in chemoselectivity is observed under neat conditions in the absence of palladium catalysis, with substitution at the 2-chloro position preferred to generate 3. Last, selective substitution of the 3-fluoro group is achieved under SNAr conditions to afford the dihalo adduct (4).
Assuntos
Hidrocarbonetos Halogenados/química , Piridinas/química , Aminação , Brometos/química , Cloretos/química , Flúor/química , Estrutura MolecularRESUMO
[reaction: see text] The reductive coupling of substituted alpha-iodomethyloxazoles and thiazoles with aliphatic aldehydes under Barbier conditions provides an effective method for the direct incorporation of intact heterocyclic systems.