Novel bradykinin-1 antagonists containing a (1,2,3,4-tetrahydro-isoquinolin-1-yl)acetic acid scaffold.
A novel B(1) antagonist core was utilized and the effects of modification of its amide side chain on the biological activity were tested. The imino functional group of isoquinolin-1-ylacetic acid and its 6,7-dimethoxy variant was sulfonylated (4-toluenesulfonyl), while the acetyl side chain was converted to amides. Three of the synthesized compounds exhibited significant activity at the recombinant human B(1) receptors in binding tests and also in a functional assay.
Huszár
József
J
Department of Medical Chemistry, University of Szeged, Szeged, Hungary.
Timár
Zoltán
Z
Szalai
Krisztina Katalin
KK
Keseru
György
G
Fülöp
Ferenc
F
Penke
Botond
B
D065168:Bradykinin Receptor Antagonists; D002118:Calcium / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005470:Fluorometry; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D044005:Tetrahydroisoquinolines / Q000737:chemistry / Q000494:pharmacology*
C532284:(1,2,3,4-tetrahydro-isoquinolin-1-yl)acetic acid; D065168:Bradykinin Receptor Antagonists; D044005:Tetrahydroisoquinolines; D002118:Calcium