Chromen-based TNF-alpha converting enzyme (TACE) inhibitors: design, synthesis, and biological evaluation.
A series of coumarin types MMP inhibitors were designed based on gelastatin hydroxamates (1) and evaluated for TACE, cellular TNF-alpha, and NO inhibitory activities. Among them, compounds 9b had potent inhibitory activities in enzymatic and cellular assays and good selectivity to MMP-2 and MMP-9. Further investigation of 9b will be carried out for its efficacy in RA animal model system.
Chun
Kwangwoo
K
Department of Biotechnology, Yonsei University, Seodaemun-gu, Seoul 120-740, Republic of Korea.
Park
Song-Kyu
SK
Kim
Hwan Mook
HM
Choi
Yongseok
Y
Kim
Myung-Hwa
MH
Park
Chun-Ho
CH
Joe
Bo-Young
BY
Chun
Tae Gyu
TG
Choi
Hyun-Moo
HM
Lee
Hee-Yoon
HY
Hong
Sung Hee
SH
Kim
Myung Sook
MS
Nam
Ky-Youb
KY
Han
Gyoonhee
G
D051722:ADAM Proteins / Q000037:antagonists & inhibitors; D000072198:ADAM17 Protein; D003374:Coumarins; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D003374:Coumarins; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein