title: MEK (MAPKK) inhibitors. Part 2: structure-activity relationships of 4-anilino-3-cyano-6,7-dialkoxyquinolines.
abstract: 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).
authors.affiliation: Chemical Sciences, Wyeth-Ayerst Research, Pearl River, NY 10965, USA. zhangn@war.wyeth.com
authors.forename: N
authors.initials: N
authors.lastname: Zhang
authors.forename: B
authors.initials: B
authors.lastname: Wu
authors.forename: N
authors.initials: N
authors.lastname: Eudy
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: F
authors.initials: F
authors.lastname: Ye
authors.forename: D
authors.initials: D
authors.lastname: Powell
authors.forename: A
authors.initials: A
authors.lastname: Wissner
authors.forename: L R
authors.initials: LR
authors.lastname: Feldberg
authors.forename: S C
authors.initials: SC
authors.lastname: Kim
authors.forename: R
authors.initials: R
authors.lastname: Mallon
authors.forename: E D
authors.initials: ED
authors.lastname: Kovacs
authors.forename: L
authors.initials: L
authors.lastname: Toral-Barza
authors.forename: C A
authors.initials: CA
authors.lastname: Kohler
mesh_terms: 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
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011804:Quinolines; D020929:Mitogen-Activated Protein Kinase Kinases