Novel adenosine receptor ligands: 1,3-disubstituted[1]benzopyrano[2,3-c]pyrazol-4-ones. Synthesis and structure-activity relationships.
A series of 1,3-disubstituted[1]benzopyrano[2,3-c]pyrazol-4-ones were synthesized and tested in vitro as A1 and A2 adenosine receptor ligands. The binding results and a molecular modelling study indicated that the presence of a proton donor group in the N6-H region of adenosine and the 7-NH region of xanthine, respectively and occupancy of the A2 lipophilic area by a moiety endowed with an electrostatic effect are essential for receptor affinity and A2-selectivity.
Colotta
V
V
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Italy.
Cecchi
L
L
Catarzi
D
D
Melani
F
F
Filacchioni
G
G
Martini
C
C
Tacchi
P
P
Lucacchini
A
A
D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000145:classification / Q000378:metabolism*; D013329:Structure-Activity Relationship
D008024:Ligands; D011720:Pyrazoles; D018047:Receptors, Purinergic P1