Tricyclic azepine derivatives as selective brain penetrant 5-HT 6 receptor antagonists

…, NJ Deeks, CN Johnson, AA Khazragi, TL Mead…

Index: Trani, Giancarlo; Baddeley, Stuart M.; Briggs, Michael A.; Chuang, Tsu T.; Deeks, Nigel J.; Johnson, Christopher N.; Khazragi, Abir A.; Mead, Tania L.; Medhurst, Andrew D.; Milner, Peter H.; Quinn, Leann P.; Ray, Alison M.; Rivers, Dean A.; Stean, Tania O.; Stemp, Geoffrey; Trail, Brenda K.; Witty, David R. Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 20 p. 5698 - 5700

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Citation Number: 17

Abstract

Starting from a benzazepine sulfonamide 5-HT6 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-HT6 receptor affinity and excellent brain: blood ratios.

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