1.
ACS Med Chem Lett
; 8(3): 378, 2017 Mar 09.
Artigo
em Inglês
| MEDLINE
| ID: mdl-28337335
RESUMO
[This corrects the article DOI: 10.1021/acsmedchemlett.6b00243.].
2.
ACS Med Chem Lett
; 7(12): 1062-1067, 2016 Dec 08.
Artigo
em Inglês
| MEDLINE
| ID: mdl-27994738
RESUMO
Human genetic evidence has identified the voltage-gated sodium channel NaV1.7 as an attractive target for the treatment of pain. We initially identified naphthalene sulfonamide 3 as a potent and selective inhibitor of NaV1.7. Optimization to reduce biliary clearance by balancing hydrophilicity and hydrophobicity (Log D) while maintaining NaV1.7 potency led to the identification of quinazoline 16 (AM-2099). Compound 16 demonstrated a favorable pharmacokinetic profile in rat and dog and demonstrated dose-dependent reduction of histamine-induced scratching bouts in a mouse behavioral model following oral dosing.