Abstract
A recently identified DPP-IV inhibitor (1) was found to induce phospholipidosis and to inhibit CYP3A4. A small series of less lipophilic and less amphiphilic analogues was synthesized in an effort to overcome these issues. One compound from this series was equipotent to 1, did not induce phospholipidosis and showed a reduced CYP3A4 inhibition.
MeSH terms
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Amines / chemistry
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Cytochrome P-450 CYP3A
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Cytochrome P-450 Enzyme Inhibitors
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Dipeptidyl Peptidase 4 / drug effects
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Dipeptidyl Peptidase 4 / metabolism*
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Humans
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Inhibitory Concentration 50
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Lipidoses / drug therapy
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Molecular Structure
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / metabolism
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Protease Inhibitors / pharmacology
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Pyrimidines / chemical synthesis*
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Pyrimidines / metabolism
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Pyrimidines / pharmacology
Substances
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Amines
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Cytochrome P-450 Enzyme Inhibitors
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Protease Inhibitors
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Pyrimidines
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aminomethylpyrimidine
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CYP3A protein, human
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Cytochrome P-450 CYP3A
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CYP3A4 protein, human
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Dipeptidyl Peptidase 4