Design and synthesis of matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold
Schröder J (2001)
Bielefeld (Germany): Bielefeld University.
Bielefelder E-Dissertation | Englisch
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Autor*in
Schröder, Jörg
Gutachter*in / Betreuer*in
Tschesche, Harald (Prof. em. Dr.)
Einrichtung
Abstract / Bemerkung
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.
Stichworte
, , Structure-based design , Matrix metalloproteinases , Thiadiazines , X-ray crystallography
Jahr
2001
Page URI
https://pub.uni-bielefeld.de/record/2301959
Zitieren
Schröder J. Design and synthesis of matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold. Bielefeld (Germany): Bielefeld University; 2001.
Schröder, J. (2001). Design and synthesis of matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold. Bielefeld (Germany): Bielefeld University.
Schröder, Jörg. 2001. Design and synthesis of matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold. Bielefeld (Germany): Bielefeld University.
Schröder, J. (2001). Design and synthesis of matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold. Bielefeld (Germany): Bielefeld University.
Schröder, J., 2001. Design and synthesis of matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold, Bielefeld (Germany): Bielefeld University.
J. Schröder, Design and synthesis of matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold, Bielefeld (Germany): Bielefeld University, 2001.
Schröder, J.: Design and synthesis of matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold. Bielefeld University, Bielefeld (Germany) (2001).
Schröder, Jörg. Design and synthesis of matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold. Bielefeld (Germany): Bielefeld University, 2001.
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