Identification of a potent new chemotype for the selective inhibition of PDE4.
A series of substituted 3,6-diphenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines were prepared and analyzed as inhibitors of phosphodiesterase 4 (PDE4). Synthesis, structure-activity relationships, and the selectivity of a highly potent analogue against related phosphodiesterase isoforms are presented.
Skoumbourdis
Amanda P
AP
NIH Chemical Genomics Center, National Human Genome Research Institute, NIH, 9800 Medical Center Drive, MSC 3370, Bethesda, MD 20892-3370, USA.
Huang
Ruili
R
Southall
Noel
N
Leister
William
W
Guo
Vicky
V
Cho
Ming-Hsuang
MH
Inglese
James
J
Nirenberg
Marshall
M
Austin
Christopher P
CP
Xia
Menghang
M
Thomas
Craig J
CJ
D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013829:Thiadiazines / Q000737:chemistry* / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*
D007527:Isoenzymes; D058988:Phosphodiesterase 4 Inhibitors; D010726:Phosphodiesterase Inhibitors; D013829:Thiadiazines; D014230:Triazoles