Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10592834 | Bioorganic & Medicinal Chemistry Letters | 2014 | 6 Pages |
Abstract
In this Letter, we describe a chemical lead optimization campaign starting from a novel, weak α7 nicotinic acetylcholine receptor positive allosteric modulator (PAM) hit from a HTS screen. Exploration of the structure-activity relationships for α7 PAM potency, intrinsic hepatic clearance, the structure-property relationships for lipophilicity, and thermodynamic solubility, led to the identification of Lu AF58801: a potent, orally available, brain penetrant PAM of the α7 nicotinic acetylcholine receptor, showing efficacy in a novel object recognition task in rats treated subchronically with phencyclidine (PCP).
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Jørgen Eskildsen, John P. Redrobe, Anette G. Sams, Kim Dekermendjian, Morten Laursen, Jette B. Boll, Roger L. Papke, Christoffer Bundgaard, Kristen Frederiksen, Jesper F. Bastlund,