SB-224289-a novel selective (human) 5-HT_1B receptor antagonist with negative intrinsic activity

摘要

Human 5-HT_1B(h5-TH_1B) and human 5-HT_1D (h5-HT_1D)receptors show remarkably similar pharmacology with few compounds discriminating the receptors. We report here on a novel compound, SB-224289(1'-Methyl-5-[[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2, 3, 6,7-tetra- Hydrospiro[furo[2,3-f]indole-3,4'-piperidine] oxalate), which has high affinity for h5-HT_1B receptors (pK_1=8.16±0.06) and displays over 75 fold selectivity for the h5-HT_1B receptor over all other 5-HT receptors including the h5-HT_1D receptor and all other receptors tested thus far.