The synthesis and characterization of BMS-204352 (MaxiPost) and related 3-fluorooxindoles as openers of maxi-K potassium channels.
3-Aryl-3-fluorooxindoles can be efficiently synthesized in two steps by the addition of an aryl Grignard to an isatin, followed by treatment with DAST. Oxindole 1 (BMS-204352; MaxiPost) can be isolated using chiral HPLC or prepared by employing chiral resolution. Cloned maxi-K channels are opened by 1, which demonstrates a brain/plasma ratio >9 in rats.
Hewawasam
Piyasena
P
Department of Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA.
Gribkoff
Valentin K
VK
Pendri
Yadagiri
Y
Dworetzky
Steven I
SI
Meanwell
Nicholas A
NA
Martinez
Eduardo
E
Boissard
Christopher G
CG
Post-Munson
Debra J
DJ
Trojnacki
Joanne T
JT
Yeleswaram
Krishnaswamy
K
Pajor
Lorraine M
LM
Knipe
Jay
J
Gao
Qi
Q
Perrone
Robert
R
Starrett
John E
JE
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D003979:Diazonium Compounds; D006801:Humans; D007211:Indoles / Q000097:blood / Q000138:chemical synthesis* / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008845:Microinjections; D009865:Oocytes / Q000187:drug effects* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014981:Xenopus
C424388:BMS204352; D003979:Diazonium Compounds; D007211:Indoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; C408750:selectfluor; D002118:Calcium