Discovery of novel quinolinone adenosine A2B antagonists.
A novel series of quinolinone-based adenosine A(2B) receptor antagonists was identified via high throughput screening of an encoded combinatorial compound collection. Synthesis and assay of a series of analogs highlighted essential structural features of the initial hit. Optimization resulted in an A(2B) antagonist (2i) which exhibited potent activity in a cAMP accumulation assay (5.1 nM) and an IL-8 release assay (0.4 nM).
Ligand Pharmaceuticals, 3000 Eastpark Boulevard Cranbury, NJ 08512, USA. bmcguinness@venenumbiodesign.com
Brian F
BF
McGuinness
Koc-Kan
KK
Ho
Tara M
TM
Stauffer
Laura L
LL
Rokosz
Neelima
N
Mannava
Steven G
SG
Kultgen
Kurt
K
Saionz
Anthony
A
Klon
Weiqing
W
Chen
Hema
H
Desai
W Lynn
WL
Rogers
Maria
M
Webb
Juxing
J
Yin
Yan
Y
Jiang
Tailong
T
Li
Hao
H
Yan
Konghua
K
Jing
Shengting
S
Zhang
Kanak Kanti
KK
Majumdar
Vikash
V
Srivastava
Samiran
S
Saha
D058917:Adenosine A2 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D043704:Receptor, Adenosine A2B / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D058917:Adenosine A2 Receptor Antagonists; D015363:Quinolones; D043704:Receptor, Adenosine A2B