1188547-06-9Relevant articles and documents
Diamine-based human histamine H3 receptor antagonists: (4-Aminobutyn-1-yl)benzylamines
Dvorak, Curt A.,Apodaca, Richard,Xiao, Wei,Jablonowski, Jill A.,Bonaventure, Pascal,Dugovic, Christine,Shelton, Jonathan,Lord, Brian,Miller, Kirsten,Dvorak, Lisa K.,Lovenberg, Timothy W.,Carruthers, Nicholas I.
experimental part, p. 4098 - 4106 (2009/12/06)
A series of (4-aminobutyn-1-yl)benzylamines were prepared and the SAR around three key areas: (1) the amine attached to the butynyl linker (R3R4N-); (2) the benzylamine moiety (R1R2N-); and (3) the point of attachment of the benzylamine group (R1R2N- in the ortho, meta, or para positions) was examined. One compound, 4-[3-(4-piperidin-1-yl-but-1-ynyl)-benzyl]-morpholine (9s) was chosen for further profiling and found to be a selective histamine H3 antagonist with desirable drug-like properties. Ex vivo receptor occupancy studies established that 9s does occupy H3 binding sites in the brain of rats after oral administration. Subcutaneous doses of 9s (10 mg/kg) given during the natural sleep phase demonstrated robust wake-promoting effects.
