Design and synthesis of conformationally-constrained MMP inhibitors.
A novel series of conformationally constrained matrix metalloprotease inhibitors was identified. The potencies observed for these inhibitors were highly dependent upon the substitution pattern on the caprolactam ring as well as the succinate moiety.
Natchus
M G
MG
Procter and Gamble Pharmaceuticals, Health Care Research Center, Mason, OH 45040, USA.
Cheng
M
M
Wahl
C T
CT
Pikul
S
S
Almstead
N G
NG
Bradley
R S
RS
Taiwo
Y O
YO
Mieling
G E
GE
Dunaway
C M
CM
Snider
C E
CE
McIver
J M
JM
Barnett
B L
BL
McPhail
S J
SJ
Anastasio
M B
MB
De
B
B
D002209:Caprolactam / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017364:Collagenases / Q000737:chemistry; D015195:Drug Design; D007202:Indicators and Reagents; D007700:Kinetics; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3 / Q000737:chemistry; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013386:Succinates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D007202:Indicators and Reagents; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013386:Succinates; D002209:Caprolactam; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1