1H-imidazo[4,5-c]quinolin-4-amines: novel non-xanthine adenosine antagonists.
On the basis of a model we recently developed for the antagonist binding site of the adenosine A1 receptor (J. Med. Chem. 1990, 33, 1708-1713), it was predicted that 1H-imidazo[4,5-c]quinolin-4-amines would be antagonists of the A1 receptor. Furthermore, it was expected that certain hydrophobic substitutions at the 2- and 4-positions would enhance affinity. Here, we report on the synthesis and the adenosine A1 and A2 receptor affinity of substituted 1H-imidazo[4,5-c]quinolin-4-amines. Some of these compounds have nanomolar affinity for the A1 receptor. The structure-activity relationships (SAR) of these compounds are discussed in relation to SAR for other adenosine receptor ligands. The 1H-imidazo[4,5-c]quinolin-4-amines constitute a novel class of non-xanthine adenosine antagonists.
van Galen
P J
PJ
Division of Medicinal Chemistry, Center for Bio-Pharmaceutical Sciences, Leiden, The Netherlands.
Nissen
P
P
van Wijngaarden
I
I
IJzerman
A P
AP
Soudijn
W
W
D000241:Adenosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000378:metabolism; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D011983:Receptors, Purinergic / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000378:metabolism
D007093:Imidazoles; D011804:Quinolines; D011983:Receptors, Purinergic; D014970:Xanthines; D019830:Adenosine-5'-(N-ethylcarboxamide); C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine