Abstract
Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous enzymes that catalyze the hydration of CO(2) to bicarbonate and protons. Inhibition of CAs has been clinically exploited for the treatment of various classes of diseases for decades, but investigating new classes of inhibitors continues to be important. We have synthesized a series of 2-amino-3-cyano-4-heteroaryl (5a-l) compounds and characterized the structures by NMR, IR and elemental analyses. We tested the ability of these compounds to inhibit two metalloenzyme human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes, hCA I and hCA II. Compounds 5d and 5b showed the best inhibition activity against hCA I (IC(50): 33 and 34 µM, respectively), and compound 5d showed the best activity against hCA II (IC(50): 56 µM).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminopyridines / chemical synthesis
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Aminopyridines / chemistry
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Aminopyridines / pharmacology*
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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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Carbonic Anhydrases / isolation & purification
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Carbonic Anhydrases / metabolism*
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Dose-Response Relationship, Drug
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Erythrocytes / enzymology
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Humans
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Molecular Structure
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Nitriles / chemical synthesis
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Nitriles / chemistry
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Nitriles / pharmacology*
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Protein Isoforms / antagonists & inhibitors
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Protein Isoforms / isolation & purification
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Protein Isoforms / metabolism
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Structure-Activity Relationship
Substances
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Aminopyridines
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Carbonic Anhydrase Inhibitors
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Nitriles
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Protein Isoforms
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Carbonic Anhydrases