TY  - THES
AB  - The discovery and optimization of a series of heterocyclic non-peptide matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold is described. A screening effort was utilized to identify some chiral 6-methyl-1,3,4-thiadiazines that are weak inhibitors of the catalytic domain of human neutrophil collagenase (cdMMP-8). Further optimization of the lead compounds produced the selective inhibitor (2R)-N-[5-(4-bromophenyl)-6H-1,3,4-thiadiazine-2-yl]-2-[(phenylsulfonyl)amino]propanamide with high affinity for MMP-9 (Ki = 40 nM). X-ray crystallographic data obtained for cdMMP-8 cocrystallized with N-allyl-5-(4-chlorophenyl)-6H-1,3,4-thiadiazine-2-amine hydrobromide gave detailed design information on binding interactions for thiadiazine-based MMP inhibitors.
DA  - 2001
KW  - ,  , Structure-based design , Matrix metalloproteinases , Thiadiazines , X-ray crystallography
LA  - eng
PY  - 2001
TI  - Design and synthesis of matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:361-4751
Y2  - 2024-11-22T02:11:06
ER  -