Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2005 Nov 1;15(21):4780-5.

Conformationally constrained N1-arylsulfonyltryptamine derivatives as 5-HT6 receptor antagonists.

Author information

1
Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA. coledc@wyeth.com

Abstract

Several series of conformationally constrained N1-arylsulfonyltryptamine derivatives were prepared and tested for 5-HT6 receptor binding affinity and ability to modulate cAMP production in a cyclase assay. The 3-piperidin-3-yl-, 3-(1-methylpyrrolidin-2-ylmethyl)-, and 3-pyrrolidin-3-yl-1H-indole arrays (8-13) appear to be able to adopt a conformation that allows high affinity 5-HT6 receptor binding, while the beta-carboline array 14 binds with a significantly weaker (10- to 100-fold) affinity. N1-Benzenesulfonyl-3-piperidin-3-yl-1H-indole 9a is a high affinity full agonist with EC50 = 24 nM. Several of the N1-arylsulfonyl-3-(1-methylpyrrolidin-2-ylmethyl)-1H-indole derivatives behave as very potent antagonists ((S)-11r, (S)-11t; IC50 = 0.8, 1.0 nM).

PMID:
16125933
DOI:
10.1016/j.bmcl.2005.07.028
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center