Selective heterocyclic amidine inhibitors of human inducible nitric oxide synthase.
The potency and selectivity of a series of 5-hetero-2-iminohexahydroazepines were examined as inhibitors of the three human NOS isoforms. The effect of ring substitution of the 5-carbon for a heteroatom is presented. Potencies (IC(50)'s) for these inhibitors are in the low micromolar range for hi-NOS with some examples exhibiting a 500x selectivity versus hec-NOS.
Moormann
A E
AE
Pharmacia, 700 Chesterfield Parkway North, St. Louis, MO 63198, USA. alan.e.moormann@pharmacia.com
Metz
S
S
Toth
M V
MV
Moore
W M
WM
Jerome
G
G
Kornmeier
C
C
Manning
P
P
Hansen
D W
DW
Pitzele
B S
BS
Webber
R K
RK
D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D013329:Structure-Activity Relationship
D001381:Azepines; D004791:Enzyme Inhibitors; D007527:Isoenzymes; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II