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Bioorg Med Chem Lett ; 21(22): 6888-94, 2011 Nov 15.
Article in English | MEDLINE | ID: mdl-21986586

ABSTRACT

We have identified and synthesized a series of imidazole containing dimerization inhibitors of inducible nitric oxide synthase (iNOS). The necessity of key imidazole and piperonyl functionality was demonstrated and SAR studies led to the identification of compound 35, which showed a dose dependant inhibition in multiple pain models, including tactile allodynia induced by spinal nerve ligation (Chung model).


Subject(s)
Enzyme Inhibitors/chemistry , Enzyme Inhibitors/therapeutic use , Hyperalgesia/drug therapy , Imidazoles/chemistry , Imidazoles/therapeutic use , Nitric Oxide Synthase Type II/antagonists & inhibitors , Pain/drug therapy , Protein Multimerization/drug effects , Animals , Enzyme Inhibitors/pharmacology , Female , Humans , Imidazoles/pharmacology , Nitric Oxide Synthase Type II/metabolism , Rats , Rats, Inbred Lew
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