Tricyclic azepine derivatives as selective brain penetrant 5-HT6 receptor antagonists.

Authors: Trani G, Baddeley SM, Briggs MA, Chuang TT, Deeks NJ, Johnson CN, Khazragi AA, Mead TL, Medhurst AD, Milner PH, Quinn LP, Ray AM, Rivers DA, Stean TO, Stemp G, Trail BK, Witty DR.
Publisher/Year: Bioorg Med Chem Lett. 2008 Oct 15;18(20):5698-700. Epub 2008 Aug 7.
Pub Med ID/Journal ID: PMID:18793848


Starting from a benzazepine sulfonamide 5-HT(6) receptor antagonist lead with limited brain penetration, application of a strategy of conformational constraint and reduction of hydrogen bond donor count led to a novel series of tricyclic derivatives with high 5-HT(6) receptor affinity and excellent brain:blood