Abstract
A novel series of potent thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV was discovered using structure-based drug design. Synthesis, structure-activity relationship, and optimization of physicochemical properties are described. Low nanomolar potency was achieved, and selected compounds with improved thermodynamic solubility showed promising in vitro inhibition of carbonic anhydrase activity in rabbit iris ciliary body homogenate.
(c) 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Benzenesulfonamides
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Carbonic Anhydrase II / antagonists & inhibitors*
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Carbonic Anhydrase II / chemistry
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Carbonic Anhydrase Inhibitors* / chemical synthesis
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Carbonic Anhydrase Inhibitors* / chemistry
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Carbonic Anhydrase Inhibitors* / pharmacology
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Crystallography, X-Ray
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Drug Design*
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Humans
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Rabbits
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Structure-Activity Relationship
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Sulfides / chemical synthesis
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Sulfides / chemistry
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Sulfides / pharmacology
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Sulfonamides / chemical synthesis
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Sulfonamides / chemistry
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Sulfonamides / pharmacology
Substances
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Carbonic Anhydrase Inhibitors
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Sulfides
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Sulfonamides
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Carbonic Anhydrase II