Selective A1-adenosine receptor antagonists identified using yeast Saccharomyces cerevisiae functional assays.
Evaluation of a biased "library" of pyrrolo[2,3-d]pyrimidines using yeast-based functional assays expressing human A1- and A2a-adenosine receptors, led to the A1 selective antagonist 4b. A direct correlation between yeast functional activity and binding data was established. Practical compounds with polar residues at C-4 of the pyrrolopyrimidine system required H-bond donor functionality for high potency.
Campbell
R M
RM
Cadus Pharmaceutical Corporation, Tarrytown, NY 10591, USA.
Cartwright
C
C
Chen
W
W
Chen
Y
Y
Duzic
E
E
Fu
J M
JM
Loveland
M
M
Manning
R
R
McKibben
B
B
Pleiman
C M
CM
Silverman
L
L
Trueheart
J
J
Webb
D R
DR
Wilkinson
V
V
Witter
D J
DJ
Xie
X
X
Castelhano
A L
AL
D001667:Binding, Competitive; D002460:Cell Line; D006801:Humans; D006860:Hydrogen Bonding; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*
D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D018047:Receptors, Purinergic P1; D011994:Recombinant Proteins