Respiratory syncytial virus fusion inhibitors. Part 6: an examination of the effect of structural variation of the benzimidazol-2-one heterocycle moiety.
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.
Combrink
Keith D
KD
Department of Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
Gulgeze
H Belgin
HB
Thuring
Jan W
JW
Yu
Kuo-Long
KL
Civiello
Rita L
RL
Zhang
Yi
Y
Pearce
Bradley C
BC
Yin
Zhiwei
Z
Langley
David R
DR
Kadow
Kathleen F
KF
Cianci
Christopher W
CW
Li
Zhufang
Z
Clarke
Junius
J
Genovesi
Eugene V
EV
Medina
Ivette
I
Lamb
Lucinda
L
Yang
Zheng
Z
Zadjura
Lisa
L
Krystal
Mark
M
Meanwell
Nicholas A
NA
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*
D000998:Antiviral Agents; C482453:BMS 433771; D001562:Benzimidazoles; D014760:Viral Fusion Proteins; C031000:benzimidazole