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.
Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA. curt.d.haffner@gsk.com
Curt D
CD
Haffner
Stephen A
SA
Thomson
Yu
Y
Guo
Kimberly
K
Petrov
Andrew
A
Larkin
Pierette
P
Banker
Gregory
G
Schaaf
Scott
S
Dickerson
Jeff
J
Gobel
Dan
D
Gillie
J Patrick
JP
Condreay
Chuck
C
Poole
Tiffany
T
Carpenter
John
J
Ulrich
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