Discovery and optimization of potent and selective functional antagonists of the human adenosine A2B receptor.
We herein report the discovery of a novel class of antagonists of the human adenosine A2B receptor. This low molecular weight scaffold has been optimized to offer derivatives with potential utility for the alleviation of conditions associated with this receptor subtype, such as nociception, diabetes, asthma and COPD. Furthermore, preliminary pharmacokinetic analysis has revealed compounds with profiles suitable for either inhaled or systemic routes of administration.
Bedford
Simon T
ST
Vernalis (R&D) Ltd, Granta Park, Cambridge, CB21 6GB, UK.
Benwell
Karen R
KR
Brooks
Teresa
T
Chen
Ijen
I
Comer
Mike
M
Dugdale
Sarah
S
Haymes
Tim
T
Jordan
Allan M
AM
Kennett
Guy A
GA
Knight
Anthony R
AR
Klenke
Burkhard
B
LeStrat
Loic
L
Merrett
Angela
A
Misra
Anil
A
Lightowler
Sean
S
Padfield
Anthony
A
Poullennec
Karine
K
Reece
Mark
M
Simmonite
Heather
H
Wong
Melanie
M
Yule
Ian A
IA
D058917:Adenosine A2 Receptor Antagonists; D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000188:drug therapy; D015195:Drug Design; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000378:metabolism
D058917:Adenosine A2 Receptor Antagonists; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; C476003:thienopyrimidine