title: Omega-carboxypyridyl substituted ureas as Raf kinase inhibitors: SAR of the amide substituent.
abstract: Bis-aryl ureas have been disclosed previously as a potent class of Raf kinase inhibitors. Modifications in the amide portion led to an improvement in aqueous solubility, an important characteristic for an oral drug. Based on this finding, we hypothesize that this portion of the molecule is directed towards the solvent in Raf-1.
authors.affiliation: Department of Chemistry Research, Bayer Research Center, 400Morgan Lane, West Haven, CT 06516, USA. uday.khire.b@bayer.com
authors.forename: Uday R
authors.initials: UR
authors.lastname: Khire
authors.forename: Donald
authors.initials: D
authors.lastname: Bankston
authors.forename: James
authors.initials: J
authors.lastname: Barbosa
authors.forename: David R
authors.initials: DR
authors.lastname: Brittelli
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Caringal
authors.forename: Robert
authors.initials: R
authors.lastname: Carlson
authors.forename: Jacques
authors.initials: J
authors.lastname: Dumas
authors.forename: Todd
authors.initials: T
authors.lastname: Gane
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Heald
authors.forename: Barbara
authors.initials: B
authors.lastname: Hibner
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Johnson
authors.forename: Michael E
authors.initials: ME
authors.lastname: Katz
authors.forename: Nancy
authors.initials: N
authors.lastname: Kennure
authors.forename: Jill
authors.initials: J
authors.lastname: Kingery-Wood
authors.forename: Wendy
authors.initials: W
authors.lastname: Lee
authors.forename: Xiao-Gao
authors.initials: XG
authors.lastname: Liu
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Lowinger
authors.forename: Ian
authors.initials: I
authors.lastname: McAlexander
authors.forename: Mary-Katherine
authors.initials: MK
authors.lastname: Monahan
authors.forename: Reina
authors.initials: R
authors.lastname: Natero
authors.forename: Joel
authors.initials: J
authors.lastname: Renick
authors.forename: Bernd
authors.initials: B
authors.lastname: Riedl
authors.forename: Hong
authors.initials: H
authors.lastname: Rong
authors.forename: Robert N
authors.initials: RN
authors.lastname: Sibley
authors.forename: Roger A
authors.initials: RA
authors.lastname: Smith
authors.forename: Donald
authors.initials: D
authors.lastname: Wolanin
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D016367:Baculoviridae / Q000235:genetics; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D012995:Solubility; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D011725:Pyridines; D011994:Recombinant Proteins; D014508:Urea; D019908:Proto-Oncogene Proteins c-raf; D048728:MAP Kinase Kinase Kinase 1; D020930:MAP Kinase Kinase Kinases; C482576:MAP3K1 protein, human