Identification of potent pyrimidine inhibitors of phosphodiesterase 7 (PDE7) and their ability to inhibit T cell proliferation.
A series of pyrimidine based inhibitors of PDE7 are discussed. The synthesis, structure-activity relationships (SAR) and selectivity against several other PDE family members as well as activity in T cells are presented. These compounds were found to have effects on T cell proliferation, however it is not clear whether the mechanism is related to PDE7 inhibition.
Guo
Junqing
J
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA. junqing.guo@bms.com
Watson
Andrew
A
Kempson
James
J
Carlsen
Marianne
M
Barbosa
Joseph
J
Stebbins
Karen
K
Lee
Deborah
D
Dodd
John
J
Nadler
Steven G
SG
McKinnon
Murray
M
Barrish
Joel
J
Pitts
William J
WJ
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D055786:Gene Knockout Techniques; D051379:Mice; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D010726:Phosphodiesterase Inhibitors; D011743:Pyrimidines; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7