Highly efficient and versatile synthesis of libraries of constrained beta-strand mimetics.
The general approach of using a bicyclic template to produce inhibitors of the protease superfamily of enzymes has been investigated. The Diels Alder cycloaddition reaction on solid support has been found to be highly efficient for the synthesis of libraries of compounds that mimic the beta-strand secondary structure of proteins. Several potent and selective inhibitors of proteases have been discovered.
Ogbu
C O
CO
Molecumetics Ltd., Bellevue, WA 98005-2199, USA.
Qabar
M N
MN
Boatman
P D
PD
Urban
J
J
Meara
J P
JP
Ferguson
M D
MD
Tulinsky
J
J
Lum
C
C
Babu
S
S
Blaskovich
M A
MA
Nakanishi
H
H
Ruan
F
F
Cao
B
B
Minarik
R
R
Little
T
T
Nelson
S
S
Nguyen
M
M
Gall
A
A
Kahn
M
M
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D053818:Chymases; D007202:Indicators and Reagents; D007610:Kallikreins / Q000037:antagonists & inhibitors; D007700:Kinetics; D008958:Models, Molecular; D019151:Peptide Library; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017433:Protein Structure, Secondary; D012697:Serine Endopeptidases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors; D014361:Trypsin Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D053802:Tryptases
D019086:Bridged Bicyclo Compounds, Heterocyclic; D007202:Indicators and Reagents; D019151:Peptide Library; D011480:Protease Inhibitors; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D007610:Kallikreins; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D013917:Thrombin; D053802:Tryptases