Synthesis and screening of conformationally restricted and conformationally free N-(tertiary aminoalkyl)dithiocarbamic acids and esters as inhibitors of neuronal nitric oxide synthase.
N-(Tertiary aminoalkyl)dithiocarbamic acids and esters were synthesized and evaluated for their ability to inhibit neuronal nitric oxide synthase. Preliminary results show these compounds are able to act at the binding site for L-arginine and the conformationally restricted esters may have a second site of activity involving the cofactor (6R)-5,6,7,8-tetrahydro-L-biopterin.
Sassaman
M B
MB
Positron Emission Tomography Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1180, USA.
Giovanelli
J
J
Sood
V K
VK
Eckelman
W C
WC
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019335:Nitroarginine / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000737:chemistry*
D004791:Enzyme Inhibitors; D013859:Thiocarbamates; D019335:Nitroarginine; D001708:Biopterins; D019001:Nitric Oxide Synthase; C003402:sapropterin