337969-31-0

Upstream product

• 13734-41-3 t-Boc-L-valine 
• 501-53-1 benzyl chloroformate 
• 293329-58-5 N-acetyloxy-1-(2,2-dimethoxyethyl)-6-oxo-2-phenyl-1,6-dihydropyrimidin-5-ylcarboxamide 
• 293329-56-3 N-hydroxy-1-(2,2-dimethoxyethyl)-6-oxo-2-phenyl-1,6-dihydropyrimidin-5-ylcarboxamide 
• 293329-59-6 5-amino-1-(2,2-dimethoxyethyl)-6-oxo-2-phenyl-1,6-dihydropyrimidine 
• 293329-60-9 [5-[(benzyloxycarbonyl)amino]-2-phenyl-6-oxo-1,6-dihydro-1-pyrimidinyl]acetaldehyde dimethyl acetal 
• 148747-59-5 5-benzyloxycarbonylamino-6-oxo-2-phenyl-1,6-dihydropyrimidin-1-ylmethylcarboxylic acid 
• 148747-58-4 [5-[(benzyloxycarbonyl)amino]-2-phenyl-6-oxo-1,6-dihydro-1-pyrimidinyl]acetaldehyde 
• 293329-57-4 1-(2,2-dimethoxyethyl)-6-oxo-2-phenyl-1,6-dihydropyrimidin-5-ylcarboxylic acid 
• 87694-52-8 tert-butyl (S)-1-(N-methoxy-N-methylcarbamoyl)-2-methylpropylcarbamate 
• 251540-54-2 {1-[(5-tert-butyl-[1,3,4]oxadiazol-2-yl)-hydroxy-methyl]-2-methyl-propyl}-carbamic acid tert-butyl ester 
• 251540-53-1 2-tert-Butyl-1,3,4-oxadiazole 
• 42826-42-6 pivalohydrazide 
• 598-98-1 Methyl pivalate 

Relevant academic research and scientific papers

Improved synthesis of a new nonpeptidic inhibitor of human neutrophil elastase

A practical method for the synthesis of ONO-6818 {2-(5-Amino-6-oxo-2-phenylhydropyrimidinyl)-N-[2-(5-tert-butyl-1,3,4-oxadiazo l-2-yl)-1-(methylethyl)-2-oxoethyl]acetamide} (1), the first clinical candidate for a nonpeptidic orally active inhibitor of hum

Development of orally active nonpeptidic inhibitors of human neutrophil elastase

5-Amino-2-phenylpyrimidin-6-ones, some of their desamino derivatives, and miscellaneous derivatives were synthesized and biologically evaluated on both in vitro activity and oral activity in an acute hemorrhagic assay. These compounds contained an α-keto-1,3,4-oxadiazole moiety to bind covalently to the Ser-195 hydroxy group of human neutrophil elastase (HNE). Among those tested, compounds 11a-c,e,i-l(F), 11d,e,k(H), 21d,e,k(F), and 21d,e(H) showed a good oral profile. RS-Mixture 3(H) was selected for clinical evaluation based on its oral potency, duration of action, enzyme selectivity, safety profile, and ease of synthesis. Structure -activity relationships (SARs) are discussed.