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Improved Synthesis of a New Nonpeptidic Inhibitor of Human Neutrophil Elastase
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2001
Year
Medicinal ChemistryHuman Neutrophil ElastaseBiochemistryLossen RearrangementNatural SciencesMedicineExplosive Curtius RearrangementDrug DevelopmentChemical BiologyPharmacologyNew Nonpeptidic InhibitorPharmaceutical ChemistryInhibitory ActivityBiomolecular EngineeringDrug Discovery
A practical method for the synthesis of ONO-6818 {2-(5-Amino-6-oxo-2-phenylhydropyrimidinyl)-N-[2-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-1-(methylethyl)-2-oxoethyl]acetamide} (1), the first clinical candidate for a nonpeptidic orally active inhibitor of human neutrophil elastase (HNE), was developed. This method includes a Lossen rearrangement instead of an explosive Curtius rearrangement and the improved preparation of the α-aminoketone.