Syntheses and evaluation of amidinobenzofuran derivatives as tryptase inhibitors.
We report the syntheses and evaluation of amidinobenzofuran derivatives as tryptase inhibitors. Among the compounds we evaluated, 1,5-Bis[4-(5-amidinobenzofuran-2-ylcarbonyl)piperazinylca rbonylmethoxy]cyclooctane 26 (AY0068) was found to be a selective and potent non-peptide inhibitor. 26 was effective in PCA reaction in rats without showing antihistaminic activity.
Ono
S
S
Exploratory Research II, Drug Discovery Laboratories, Yoshitomi Pharmaceutical Industries, LTD., Hirakata, Osaka, Japan.
Kuwahara
S
S
Takeuchi
M
M
Sakashita
H
H
Naito
Y
Y
Kondo
T
T
D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D053818:Chymases; D004353:Drug Evaluation, Preclinical; D051381:Rats; D012697:Serine Endopeptidases / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D053802:Tryptases
D001572:Benzofurans; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; C509223:Tpsab1 protein, rat; C509221:Tpsb2 protein, rat; D053802:Tryptases