[Synthesis, pharmacological activity and biopharmaceutical characteristics of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetates].
The pro-drugs of alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid(I) with a potent anti-inflammatory activity were synthesized in order to reduce its gastrointestinal side effects. Various esters synthesized were evaluated for their anti-inflammatory activity and ulcerogenicity. Among the compounds maintaining a potent activity of I, N,N-dimethylcarbamoylmethyl alpha,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetate (II-18) showed excellent biopharmaceutical characteristics. The ulcerogenic effect of II-18 on the rat gastric mucosa was about 3 times less than that of I. It was suggested that II-18 may be an useful biolabile pro-drug for I among the compounds tested.
Kawasaki
K
K
Yamada
I
I
Oe
T
T
Tsuruda
M
M
Terasawa
M
M
Imayoshi
T
T
Yasunaga
Y
Y
Goto
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans / Q000138:chemical synthesis / Q000494:pharmacology*; D001682:Biological Availability; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D011355:Prodrugs; C062726:tilnoprofenic acid