A new orally bioavailable dual adenosine A2B/A3 receptor antagonist with therapeutic potential.
The synthesis and SAR of 5-heterocycle-substituted aminothiazole adenosine receptor antagonists is described. Several compounds show high affinity and selectivity for the A2B and A3 receptors. One compound (5f) shows good ADME properties in the rat and as such may be an important new compound in testing the current hypotheses proposing a therapeutic role for a dual A2B/A3 antagonist in allergic diseases.
Press
Neil J
NJ
Novartis Institutes for Biomedical Research, Respiratory Diseases Area, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK. neil.press@novartis.com
Taylor
Roger J
RJ
Fullerton
Joseph D
JD
Tranter
Pamela
P
McCarthy
Clive
C
Keller
Thomas H
TH
Brown
Lyndon
L
Cheung
Robert
R
Christie
Julie
J
Haberthuer
Sandra
S
Hatto
Julia D I
JD
Keenan
Mark
M
Mercer
Mark K
MK
Press
Nicola E
NE
Sahri
Helene
H
Tuffnell
Andrew R
AR
Tweed
Morris
M
Fozard
John R
JR
D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D043684:Receptor, Adenosine A3 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology
D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D006571:Heterocyclic Compounds; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D013844:Thiazoles