5-HT(6) receptor antagonists: lead optimisation and biological evaluation of N-aryl and N-heteroaryl 4-amino-benzene sulfonamides

M Bös; A J Sleight; T Godel; J R Martin; C Riemer; H Stadler

doi:10.1016/s0223-5234(00)01209-5

5-HT(6) receptor antagonists: lead optimisation and biological evaluation of N-aryl and N-heteroaryl 4-amino-benzene sulfonamides

Eur J Med Chem. 2001 Feb;36(2):165-78. doi: 10.1016/s0223-5234(00)01209-5.

Authors

M Bös¹, A J Sleight, T Godel, J R Martin, C Riemer, H Stadler

Affiliation

¹ Boehringer Ingelheim (Canada) Ltd, Research & Development, 2100 Cunard Street, Laval, H7S 2G5, Québec, Canada. [email protected]

PMID: 11311747
DOI: 10.1016/s0223-5234(00)01209-5

Abstract

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.

MeSH terms

Animals
Binding, Competitive
Biological Availability
Humans
Memory Disorders / chemically induced
Memory Disorders / drug therapy
Protein Binding
Pyrimidines
Rats
Receptors, Serotonin / metabolism*
Scopolamine
Serotonin Antagonists / chemical synthesis*
Serotonin Antagonists / pharmacokinetics
Serotonin Antagonists / pharmacology*
Sulfanilamide
Sulfanilamides / chemical synthesis
Sulfanilamides / pharmacokinetics
Sulfanilamides / pharmacology

Substances

Pyrimidines
Receptors, Serotonin
Ro 4-6790
Serotonin Antagonists
Sulfanilamides
serotonin 6 receptor
Sulfanilamide
Scopolamine