5-HT(6) receptor antagonists: lead optimisation and biological evaluation of N-aryl and N-heteroaryl 4-amino-benzene sulfonamides.
RO-04-6790 (6a) has been identified in a random screen for 5-HT(6) receptor antagonists. In a medicinal chemistry optimisation program a series of analogs comprising N-heteroaryl- and N-arylbenzenesulfonamides have been synthesised and investigated for their binding affinity. Compounds with a logD profile indicative of brain penetration have been subjected to in vivo testing for reversal of a scopolamine-induced retention deficit in a passive avoidance paradigm.
Bös
M
M
Boehringer Ingelheim (Canada) Ltd, Research & Development, 2100 Cunard Street, Laval, H7S 2G5, Québec, Canada. mboes@lav.boehringer-ingelheim.com
Sleight
A J
AJ
Godel
T
T
Martin
J R
JR
Riemer
C
C
Stadler
H
H
D000818:Animals; D001667:Binding, Competitive; D001682:Biological Availability; D006801:Humans; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy; D011485:Protein Binding; D011743:Pyrimidines; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D012601:Scopolamine; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077145:Sulfanilamide; D013424:Sulfanilamides / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D000096926:Benzenesulfonamides
D011743:Pyrimidines; D011985:Receptors, Serotonin; D012601:Scopolamine; D012702:Serotonin Antagonists; D000077145:Sulfanilamide; D013424:Sulfanilamides; C114163:Ro 4-6790; D000096926:Benzenesulfonamides; C097216:serotonin 6 receptor