Synthesis and biological effects of a new series of 2-amino-3-benzoylthiophenes as allosteric enhancers of A1-adenosine receptor.
New derivatives of PD 81,723, an allosteric enhancer of agonist binding to the A1-adenosine receptor, have been synthesized and evaluated in an intact cell assay. Compounds 3a, 3o and 3p appeared to be more potent than PD 81,723 and at a concentration of 0.1 microM caused significant reductions of cAMP content of CHO cells expressing the human A1-adenosine receptor. Compounds 4e and 4o appeared to be allosteric enhancers at a low concentration and antagonists at a higher concentration, whereas compounds 3c, 3g, 3s and 4l appeared to be weak antagonists that are also allosteric enhancers at the higher concentration of 10 microM.
Baraldi
P G
PG
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Italy. pgb@dns.unife.it
Zaid
A N
AN
Lampronti
I
I
Fruttarolo
F
F
Pavani
M G
MG
Tabrizi
M A
MA
Shryock
J C
JC
Leung
E
E
Romagnoli
R
R
D000494:Allosteric Regulation; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000032:analysis; D006801:Humans; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology
D018047:Receptors, Purinergic P1; D013876:Thiophenes; C075004:PD 81723; D000242:Cyclic AMP