Benzenesulfonamide derivatives of 2-substituted 4H-3,1-benzoxazin-4-ones and benzthiazin-4-ones as inhibitors of complement C1r protease.
A series of 2-sulfonyl-4H-3,1-benzoxazinones was prepared that inhibit C1r protease in vitro. Several compounds were found to be selective for C1r verses the related serine protease trypsin. Selected compounds demonstrated functional activity in a hemolysis assay.
Plummer
J S
JS
Department of Chemistry, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
Cai
C
C
Hays
S J
SJ
Gilmore
J L
JL
Emmerling
M R
MR
Michael
W
W
Narasimhan
L S
LS
Watson
M D
MD
Wang
K
K
Nath
R
R
Evans
L M
LM
Jaen
J C
JC
D000818:Animals; D003174:Complement C1 Inactivator Proteins / Q000138:chemical synthesis*; D015923:Complement C1r / Q000037:antagonists & inhibitors; D004912:Erythrocytes / Q000187:drug effects; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D012756:Sheep; D013449:Sulfonamides / Q000138:chemical synthesis*; D000096926:Benzenesulfonamides
D003174:Complement C1 Inactivator Proteins; D015923:Complement C1r; D013449:Sulfonamides; D000096926:Benzenesulfonamides