Benzamide derivatives as blockers of Kv1.3 ion channel.
The voltage-gated potassium channel, Kv1.3, is present in human T-lymphocytes. Blockade of Kv1.3 results in T-cell depolarization, inhibition of T-cell activation, and attenuation of immune responses in vivo. A class of benzamide Kv1.3 channel inhibitors has been identified. The structure-activity relationship within this class of compounds in two functional assays, Rb_Kv and T-cell proliferation, is presented. In in vitro assays, trans isomers display moderate selectivity for binding to Kv1.3 over other Kv1.x channels present in human brain.
Miao
Shouwu
S
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. bao_jianming@merck.com
Bao
Jianming
J
Garcia
Maria L
ML
Goulet
Joung L
JL
Hong
Xingfang J
XJ
Kaczorowski
Gregory J
GJ
Kayser
Frank
F
Koo
Gloria C
GC
Kotliar
Andrew
A
Schmalhofer
William A
WA
Shah
Kashmira
K
Sinclair
Peter J
PJ
Slaughter
Robert S
RS
Springer
Marty S
MS
Staruch
Mary Jo
MJ
Tsou
Nancy N
NN
Wong
Frederick
F
Parsons
William H
WH
Rupprecht
Kathleen M
KM
D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated; D012414:Rubidium Radioisotopes; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
D001549:Benzamides; C496973:KCNA3 protein, human; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012414:Rubidium Radioisotopes