Identification of a potent and selective 5-HT1B receptor antagonist

An SAR study around the mixed 5-HT1ABD receptor antagonist SB-272183 found that introduction of cis-2,6-dimethyl substitution onto the piperazine ring was a key structural change, which imparted a combination of both excellent selectivity over the 5-HT1A and 5-HT1D receptors and low intrinsic activity. This led to the identification of the selective 5-HT1B receptor antagonist SB-616234.

Graphical abstractIntroduction of cis-2,6-dimethyl substitution onto the piperazine ring of a mixed 5-HT1ABD receptor antagonist offers a combination of both excellent selectivity over 5-HT1A and 5-HT1D receptors and low intrinsic activity.Figure optionsDownload full-size imageDownload as PowerPoint slide