title: Identification and SAR of selective inducible nitric oxide synthase (iNOS) dimerization inhibitors.
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).
authors: Department of Medicinal Chemistry, Kalypsys Inc., 10420 Wateridge Circle, San Diego, CA 92121, USA. tgahman@gmail.com
authors: Timothy C
authors: TC
authors: Gahman
authors: Mark R
authors: MR
authors: Herbert
authors: Henk
authors: H
authors: Lang
authors: Angie
authors: A
authors: Thayer
authors: Kent T
authors: KT
authors: Symons
authors: Phan Manh
authors: PM
authors: Nguyen
authors: Mark E
authors: ME
authors: Massari
authors: Sara
authors: S
authors: Dozier
authors: Yan
authors: Y
authors: Zhang
authors: Marciano
authors: M
authors: Sablad
authors: Tadimeti S
authors: TS
authors: Rao
authors: Stewart A
authors: SA
authors: Noble
authors: Andrew K
authors: AK
authors: Shiau
authors: Christian A
authors: CA
authors: Hassig
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy*; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010146:Pain / Q000188:drug therapy*; D055503:Protein Multimerization / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D052247:Nitric Oxide Synthase Type II