Novel CXCR3 antagonists with a piperazinyl-piperidine core.
High-throughput screening of an encoded combinatorial aryl piperazine library led to the identification of a novel series of potent piperazinyl-piperidine based CXCR3 antagonists. Analogs of the initial hit were synthesized via solid and solution phase methods to probe the influence of structure on the CXCR3 binding of these molecules. Various functional groups were found to contribute to the overall potency and essential molecular features were identified.
McGuinness
Brian F
BF
Ligand Pharmaceuticals, 3000 Eastpark Boulevard, Cranbury, NJ 08512, USA. bmcguinness@ligand.com
Carroll
Carolyn DiIanni
CD
Zawacki
Lisa Guise
LG
Dong
Guizhen
G
Yang
Cangming
C
Hobbs
Doug W
DW
Jacob-Samuel
Biji
B
Hall
James W
JW
Jenh
Chung-Her
CH
Kozlowski
Joseph A
JA
Anilkumar
Gopinadhan N
GN
Rosenblum
Stuart B
SB
D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D054367:Receptors, CXCR3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D010879:Piperazines; D010880:Piperidines; D054367:Receptors, CXCR3