Substituted N-{3-[(1,1-dioxido-1,2-benzothiazol-3-yl)(phenyl)amino]propyl}benzamide analogs as potent Kv1.3 ion channel blockers. Part 2.
We report the synthesis and in vitro activity of a series of novel substituted 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 demonstrated similar potency to the known Kv1.3 inhibitor PAP-1 when tested under the IonWorks patch clamp assay conditions. Two compounds 13i and 13rr were advanced further as potential tool compounds for in vivo validation studies.
Haffner
Curt D
CD
Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA. curt.d.haffner@gsk.com
Thomson
Stephen A
SA
Guo
Yu
Y
Petrov
Kimberly
K
Larkin
Andrew
A
Banker
Pierette
P
Schaaf
Gregory
G
Dickerson
Scott
S
Gobel
Jeff
J
Gillie
Dan
D
Condreay
J Patrick
JP
Poole
Chuck
C
Carpenter
Tiffany
T
Ulrich
John
J
D000577:Amides; D000818:Animals; D001549:Benzamides / Q000737:chemistry* / Q000494:pharmacology*; D052160:Benzothiazoles / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors*; D000073718:Pancreatitis-Associated Proteins; D018408:Patch-Clamp Techniques; D051381:Rats; D013329:Structure-Activity Relationship
D000577:Amides; D001549:Benzamides; D052160:Benzothiazoles; D051664:Kv1.3 Potassium Channel; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human