Benzenesulfonamide derivatives of 2-substituted 4H-3,1-benzoxazin-4-ones and benzthiazin-4-ones as inhibitors of complement C1r protease

J S Plummer; C Cai; S J Hays; J L Gilmore; M R Emmerling; W Michael; L S Narasimhan; M D Watson; K Wang; R Nath; L M Evans; J C Jaen

doi:10.1016/s0960-894x(99)00095-5

Benzenesulfonamide derivatives of 2-substituted 4H-3,1-benzoxazin-4-ones and benzthiazin-4-ones as inhibitors of complement C1r protease

Bioorg Med Chem Lett. 1999 Mar 22;9(6):815-20. doi: 10.1016/s0960-894x(99)00095-5.

Authors

J S Plummer¹, C Cai, S J Hays, J L Gilmore, M R Emmerling, W Michael, L S Narasimhan, M D Watson, K Wang, R Nath, L M Evans, J C Jaen

Affiliation

¹ Department of Chemistry, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.

PMID: 10206542
DOI: 10.1016/s0960-894x(99)00095-5

Abstract

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.

MeSH terms

Animals
Benzenesulfonamides
Complement C1 Inactivator Proteins / chemical synthesis*
Complement C1r / antagonists & inhibitors
Erythrocytes / drug effects
Inhibitory Concentration 50
Kinetics
Models, Chemical
Sheep
Sulfonamides / chemical synthesis*

Substances

Complement C1 Inactivator Proteins
Sulfonamides
Complement C1r