Interaction of chiral MS-245 analogs at h5-HT6 receptors

Optically active pyrrolidinylmethylindole analogs related in structure to the benzenesulfonyltryptamine 5-HT6 receptor antagonist MS-245 were evaluated and their R-isomers were found to bind with affinity higher than their S-enantiomers.

Chiral analogs of the 5-HT6 ligand MS-245 (Ki ca. 2 nM) were examined; for example, 5d (Ki = 0.3 nM) binds with higher affinity than its S-enantiomer (Ki = 1.7 nM), and with 30 times greater affinity than its counterpart lacking the benzenesulfonyl group.Figure optionsDownload as PowerPoint slide