N-Sulfamoylphenyl- and N-sulfamoylphenyl-N-thiazolyl-ß-alanines and their derivatives as inhibitors of human carbonic anhydrases.
Bioorg Chem
; 75: 16-29, 2017 12.
Article
em En
| MEDLINE
| ID: mdl-28888097
ABSTRACT
A series of N-substituted and N,N-disubstituted ß-amino acids and their derivatives bearing benzenesulfonamide moiety were designed and synthesized in search of compounds that would be high-affinity and selective inhibitors of human carbonic anhydrases (CA). There are 12 catalytically active human CA isoforms, the cytosolic CA I, CA II, CA III, CA VII, and CA XIII, secreted CA VI, the mitochondrial CA VA and CA VB, membrane-associated CA IV, and transmembrane CA IX, CA XII, and CA XIV. The di-bromo meta-substituted compounds exhibited low nanomolar dissociation constants and over 10-fold selectivity for mitochondrial isozyme CA VB, implicated in diseases of the central nervous system and obesity. These compounds can be used for further development as inhibitors of significant binding affinity and selectivity towards CA VB isozyme.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Inibidores da Anidrase Carbônica
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Anidrases Carbônicas
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Alanina
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Isoenzimas
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article