Salicylamide inhibitors of influenza virus fusion.
Structural variation of the quinolizidine heterocycle of the influenza fusion inhibitor BMY-27709 was examined by several topological dissections in order to illuminate the critical features of the ring system. This exercise resulted in the identification of a series of synthetically more accessible decahydroquinolines that retained the structural elements of BMY-27709 important for antiviral activity. The 2-methyl-cis-decahydroquinoline 6f was the most potent influenza inhibitor identified that demonstrated an EC50 of 90 ng/mL in a plaque reduction assay.
Department of Chemistry, The Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 05492, USA. keith.combrink@bms.com
K D
KD
Combrink
H B
HB
Gulgeze
K L
KL
Yu
B C
BC
Pearce
A K
AK
Trehan
J
J
Wei
M
M
Deshpande
M
M
Krystal
A
A
Torri
G
G
Luo
C
C
Cianci
S
S
Danetz
L
L
Tiley
N A
NA
Meanwell
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004285:Dogs; D008561:Membrane Fusion / Q000187:drug effects*; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000502:physiology; D011807:Quinolizines / Q000737:chemistry / Q000494:pharmacology*; D012457:Salicylamides / Q000737:chemistry / Q000494:pharmacology*
D000998:Antiviral Agents; C105257:BMY 27709; D011807:Quinolizines; D012457:Salicylamides; C031060:salicylamide