Design and synthesis of carboxylate inhibitors for matrix metalloproteinases.
Chem Pharm Bull (Tokyo)
; 49(10): 1272-9, 2001 Oct.
Article
in En
| MEDLINE
| ID: mdl-11605653
ABSTRACT
A series of carboxylate compounds were prepared from N(alpha)-substituted 2,3-diaminopropionic acid and were tested for efficacy as matrix metalloproteinase (MMP) inhibitors. During modeling of the initial compound 10a, we utilized three-dimensional structure modeling software (InsightII/Discover Ver. 2.98). Some of the prepared carboxylate derivatives, such as carbamate compounds (12c,d, 22) and sulfonamide compounds (14b,c), proved to be effective MMP-1 inhibitors (with IC50 values of a 10(-6) M order), depending on the substituent at the N(alpha)-position of 2,3-diaminopropionic acid. Some of them were also evaluated for inhibition of stromelysin-1 (MMP-3), and the sulfonamide compound 14c exceeded the lead compound 5b in its MMP-3 inhibitory potency. For the carbamate compounds, we investigated the minimum molecular size at which the MMP-1 inhibitory potency was maintained, and found that this was P3-P1' compound 10b.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carboxylic Acids
/
Enzyme Inhibitors
/
Matrix Metalloproteinase Inhibitors
Language:
En
Journal:
Chem Pharm Bull (Tokyo)
Year:
2001
Document type:
Article
Affiliation country:
Japan
Publication country:
JAPAN
/
JAPON
/
JAPÃO
/
JP