MEK (MAPKK) inhibitors. Part 2: structure-activity relationships of 4-anilino-3-cyano-6,7-dialkoxyquinolines.
A series of 4-anilino-3-cyano-6,7-dialkoxyquinolines with different substituents attached to the 4-anilino group has been prepared that are potent MEK (MAP kinase kinase) inhibitors. The best activity is obtained when a phenyl or a thienyl group is attached to the para-position of the aniline through a hydrophobic linker, such as an oxygen, a sulfur, or a methylene group. The most active compounds show low nanomolar IC(50)'s against MEK (MAP kinase kinase), and have potent growth inhibitory activity in LoVo cells (human colon tumor line).
Zhang
N
N
Chemical Sciences, Wyeth-Ayerst Research, Pearl River, NY 10965, USA. zhangn@war.wyeth.com
Wu
B
B
Eudy
N
N
Wang
Y
Y
Ye
F
F
Powell
D
D
Wissner
A
A
Feldberg
L R
LR
Kim
S C
SC
Mallon
R
R
Kovacs
E D
ED
Toral-Barza
L
L
Kohler
C A
CA
D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000814:Aniline Compounds; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011804:Quinolines; D020929:Mitogen-Activated Protein Kinase Kinases