Syntheses and evaluation of amidinobenzofuran derivatives as tryptase inhibitors

S Ono; S Kuwahara; M Takeuchi; H Sakashita; Y Naito; T Kondo

doi:10.1016/s0960-894x(99)00594-6

Syntheses and evaluation of amidinobenzofuran derivatives as tryptase inhibitors

Bioorg Med Chem Lett. 1999 Dec 6;9(23):3285-90. doi: 10.1016/s0960-894x(99)00594-6.

Authors

S Ono¹, S Kuwahara, M Takeuchi, H Sakashita, Y Naito, T Kondo

Affiliation

¹ Exploratory Research II, Drug Discovery Laboratories, Yoshitomi Pharmaceutical Industries, LTD., Hirakata, Osaka, Japan.

PMID: 10612586
DOI: 10.1016/s0960-894x(99)00594-6

Abstract

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.

MeSH terms

Animals
Benzofurans / chemical synthesis*
Benzofurans / chemistry
Benzofurans / pharmacology*
Chymases
Drug Evaluation, Preclinical
Rats
Serine Endopeptidases / drug effects*
Serine Proteinase Inhibitors / chemical synthesis*
Serine Proteinase Inhibitors / chemistry
Serine Proteinase Inhibitors / pharmacology*
Structure-Activity Relationship
Tryptases

Substances

Benzofurans
Serine Proteinase Inhibitors
Serine Endopeptidases
chymase 2
Chymases
Tpsab1 protein, rat
Tpsb2 protein, rat
Tryptases