N-{3-[(1,1-dioxido-1,2-benzothiazol-3-yl)(phenyl)amino]propyl}benzamide analogs as potent Kv1.3 inhibitors. Part 1

Curt D Haffner; Stephen A Thomson; Yu Guo; Lee T Schaller; Sharon Boggs; Scott Dickerson; Jeff Gobel; Dan Gillie; J Patrick Condreay

doi:10.1016/j.bmcl.2010.09.132

N-{3-[(1,1-dioxido-1,2-benzothiazol-3-yl)(phenyl)amino]propyl}benzamide analogs as potent Kv1.3 inhibitors. Part 1

Bioorg Med Chem Lett. 2010 Dec 1;20(23):6983-8. doi: 10.1016/j.bmcl.2010.09.132. Epub 2010 Oct 7.

Authors

Curt D Haffner¹, Stephen A Thomson, Yu Guo, Lee T Schaller, Sharon Boggs, Scott Dickerson, Jeff Gobel, Dan Gillie, J Patrick Condreay

Affiliation

¹ Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA. [email protected]

PMID: 20971642
DOI: 10.1016/j.bmcl.2010.09.132

Abstract

We report the synthesis and in vitro activity of a series of novel N-{3-[(1,1-dioxido-1,2-benzothiazol-3-yl)(phenyl)amino]propyl}benzamide analogs. These analogs showed potent inhibitory activity against Kv1.3. Several compounds, including compound 8b, showed similar potency to the known Kv1.3 inhibitor PAP-1 when tested under the IonWorks patch clamp assay conditions.

MeSH terms

Amides
Animals
Benzamides / chemistry*
Benzamides / pharmacology
Benzothiazoles / chemistry*
Benzothiazoles / pharmacology
Cell Line
Humans
Kv1.3 Potassium Channel / antagonists & inhibitors*
Pancreatitis-Associated Proteins
Patch-Clamp Techniques
Structure-Activity Relationship
Sulfonamides
Urea / analogs & derivatives

Substances

Amides
Benzamides
Benzothiazoles
Kv1.3 Potassium Channel
Pancreatitis-Associated Proteins
REG3A protein, human
Sulfonamides
Urea