bms-433771 and benzimidazole

Several non-benzimidazole containing inhibitors of respiratory syncytial virus are described. Core template modification, analysis of antiviral activity, physicochemistry and optimisation of properties led to the thiazole-imidazole 13, that showed a good potency and pharmacokinetic profile in the rat.

Topics: Animals; Antiviral Agents; Benzimidazoles; Imidazoles; Inhibitory Concentration 50; Rats; Respiratory Syncytial Viruses; Structure-Activity Relationship; Thiazoles

The effect of structural variation of the benzimidazol-2-one ring of RSV fusion inhibitors related to BMS-433771 (1) was examined in conjunction with side chain modifications and the introduction of an aminomethyl substituent at the 5-position of the core benzimidazole moiety. Replacement of the benzimidazol-2-one moiety with benzoxazole, oxindole, quinoline-2-one, quinazolin-2,4-dione and benzothiazine derivatives provided a series of potent RSV fusion inhibitors 4. However, the intrinsic potency of 6,6-fused ring systems was generally less than that of comparably substituted 5,6-fused heterocycles of the type found in BMS-433771 (1). The introduction of an aminomethyl substituent to the benzimidazole ring enhanced antiviral activity in the 6,6-fused ring systems.

Topics: Antiviral Agents; Benzimidazoles; Chemistry, Pharmaceutical; Drug Design; Electrons; Humans; Inhibitory Concentration 50; Models, Chemical; Models, Molecular; Molecular Conformation; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Viral Fusion Proteins