title: Respiratory syncytial virus fusion inhibitors. Part 6: an examination of the effect of structural variation of the benzimidazol-2-one heterocycle moiety.
abstract: 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.
authors.affiliation: Department of Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
authors.forename: Keith D
authors.initials: KD
authors.lastname: Combrink
authors.forename: H Belgin
authors.initials: HB
authors.lastname: Gulgeze
authors.forename: Jan W
authors.initials: JW
authors.lastname: Thuring
authors.forename: Kuo-Long
authors.initials: KL
authors.lastname: Yu
authors.forename: Rita L
authors.initials: RL
authors.lastname: Civiello
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Pearce
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Yin
authors.forename: David R
authors.initials: DR
authors.lastname: Langley
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Kadow
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Cianci
authors.forename: Zhufang
authors.initials: Z
authors.lastname: Li
authors.forename: Junius
authors.initials: J
authors.lastname: Clarke
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Genovesi
authors.forename: Ivette
authors.initials: I
authors.lastname: Medina
authors.forename: Lucinda
authors.initials: L
authors.lastname: Lamb
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.forename: Lisa
authors.initials: L
authors.lastname: Zadjura
authors.forename: Mark
authors.initials: M
authors.lastname: Krystal
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Meanwell
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004583:Electrons; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy*; D012136:Respiratory Syncytial Viruses / Q000378:metabolism*; D014760:Viral Fusion Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000998:Antiviral Agents; C482453:BMS 433771; D001562:Benzimidazoles; D014760:Viral Fusion Proteins; C031000:benzimidazole