Synthesis and SAR of alpha-sulfonylcarboxylic acids as potent matrix metalloproteinase inhibitors.
A series of novel carboxylic acid-based alpha-sulfone MMP inhibitors have been synthesized and the in vitro enzyme SAR is discussed. A potential binding mode in the active site of the MMP-9 homology model was highlighted. These compounds are potent MMP-9 inhibitors and are selective over MMP-1.
Zhang
Yue-Mei
YM
Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, 1000 Route 202, Raritan, NJ 08869, USA. xufangymz@yahoo.com
Fan
Xiaodong
X
Xiang
Bangping
B
Chakravarty
Devraj
D
Scannevin
Robert
R
Burke
Sharon
S
Karnachi
Prabha
P
Rhodes
Kenneth
K
Jackson
Paul
P
D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013455:Sulfur / Q000737:chemistry*
D002264:Carboxylic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013455:Sulfur; D020782:Matrix Metalloproteinases