3-Aryl-4-hydroxyquinolin-2(1H)-one derivatives as type I fatty acid synthase inhibitors.
A series of 3-aryl-4-hydroxyquinolin-2(1H)-ones with fatty acid synthase inhibitory activity was prepared. Starting from a derivative with an IC(50) = 1.4 microM, SAR studies led to compounds with more than 70-fold increase in potency (IC(50) < 20 nM).
Rivkin
Alexey
A
Department of Chemistry, Merck Research Laboratories, Boston, MA 02115, USA. alexey_rivkin@merck.com
Kim
Yoona R
YR
Goulet
Mark T
MT
Bays
Nathan
N
Hill
Armetta D
AD
Kariv
Ilona
I
Krauss
Stefan
S
Ginanni
Nicole
N
Strack
Peter R
PR
Kohl
Nancy E
NE
Chung
Christine C
CC
Varnerin
Jeffrey P
JP
Goudreau
Paul N
PN
Chang
Amy
A
Tota
Michael R
MR
Munoz
Benito
B
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D006912:Hydroxyquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008314:Malonates / Q000737:chemistry; D008872:Microwaves; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D006912:Hydroxyquinolines; D008314:Malonates; D011804:Quinolines; D064429:Fatty Acid Synthases