Novel 2-aminobenzothiazoles as selective neuronal nitric oxide synthase inhibitors.
A series of substituted 2-aminobenzothiazole compounds have been synthesized and evaluated as nitric oxide synthase (NOS) inhibitors. Compound 14 shows activity in the nM range and is selective for the human neuronal NOS isoform. We have also evaluated the compounds against the rat NOS isoforms. For some of the compounds, there are significant differences in NOS inhibitory activities between the human and rat enzymes. For example, compound 10b has nM activity against the rat nNOS while low microM activity against the human nNOS.
Patman
Joanne
J
NeurAxon Inc. Suite 318, 16-1375 Southdown Road, Mississauga, Ont., Canada L5J 2Z1.
Bhardwaj
Namrta
N
Ramnauth
Jailall
J
Annedi
Subhash C
SC
Renton
Paul
P
Maddaford
Shawn P
SP
Rakhit
Suman
S
Andrews
John S
JS
D000818:Animals; D052160:Benzothiazoles / Q000737:chemistry* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes; D008956:Models, Chemical; D008968:Molecular Conformation; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D051381:Rats; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D013844:Thiazoles; D052248:Nitric Oxide Synthase Type I