Syntheses and evaluation of pyrido[2,3-dlpyrimidine-2,4-diones as PDE 4 inhibitors.
The syntheses and in vitro evaluation of a new series of pyrido[2,3-d]pyrimidine-2,4-diones bearing substituents at C-3 and/or C-4 positions on the pyridine ring are described. Some of these compounds, especially 51 and 6f, were found to be potent phosphodiesterase 4 (PDE 4) inhibitors exhibiting improved ratio of PDE 4 inhibitory activity:rolipram binding assay (RBA).
Nam
G
G
Biochemicals Research Center, Korea Institute of Science and Technology, Cheongryang, Seoul, South Korea.
Yoon
C M
CM
Kim
E
E
Rhee
C K
CK
Kim
J H
JH
Shin
J H
JH
Kim
S H
SH
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001681:Biological Assay; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006801:Humans; D015394:Molecular Structure; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D020889:Rolipram / Q000378:metabolism
C092843:CP 77059; D010726:Phosphodiesterase Inhibitors; D011743:Pyrimidines; D011799:Quinazolines; C096328:RS 25344; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram