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KMID : 0614020030180010001
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Journal of Pharmaceutical Sciences (C.N.U.)
2003 Volume.18 No. 1 p.1 ~ p.11
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Evaluation of Importance of Hydroxamic Acid Moiety of 2-(benzenesulfonamido)-N-hydroxy-3-phenylpropionamide for Its MMP2 Inhibitory Activity
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Jung Sang-Hun
Park Hyun
Cho Gook-Hyun
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Abstract
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Gelatinases A (MMP-2) and B (MMP-9) containing Zinc are considered to be a valuable target for the prevention of metastasis and formation of new vessel. (R)-2-(Benzenesulfonamido)-N-hydroxy-3-phenylpropionamide (1) had been identified as a simple and potent inhibitor of these enzymes. This compound has hydroxamic acid moiety which chelate Zinc very efficiently However its chemical instability producing carcinogenic hydroxylamine in vivo has been an issue for the development of its clinical utility. To avoid generation of its hazardous metabolite, the possibility of replacement of hydroxamic acid moiety with other functional groups containing ability to bind Zinc was investigated Thus compounds containing mercapto (7), benzenesulfonamido (10), benzamido (11), cyclohexylureido (12), or 4-chlorobenzenesulfonylureido (13) were prepared and their inhibitory activity were tested against gelatinase A. None of these compounds show the inhibitory activity of gelatinase A. This indicates that hydroxamic acid like small moiety- at this region is essential for the inhibitory activity against these enzymes.
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KEYWORD
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MMP2 inhibitor, 2-(benzenesulfonamido)-N-hydroxy-3-phenylpropionamide, hydroxamic acid
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