title: Synthesis and structure-activity relationship of 2-arylamino-4-aryl-pyrimidines as potent PAK1 inhibitors.
abstract: 2-Arylamino-4-aryl-pyrimidines were found to be potent inhibitors of PAK1 kinase. The synthesis and SAR are described. The incorporation of a bromide at the 5-position of the pyrimidine core and in combination with a 1,2-dimethylpiperazine pendant domain yielded a lead compound with potent PAK1 inhibition and anti-proliferative activity in various colon cancer cell lines.
authors.affiliation: Astex Pharmaceuticals, Inc., 4140 Dublin Boulevard, Suite 200, Dublin, CA 94568, USA. yxu22@hotmail.com
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Jason M
authors.initials: JM
authors.lastname: Foulks
authors.forename: Adrianne
authors.initials: A
authors.lastname: Clifford
authors.forename: Benjamin
authors.initials: B
authors.lastname: Brenning
authors.forename: Shuping
authors.initials: S
authors.lastname: Lai
authors.forename: Bai
authors.initials: B
authors.lastname: Luo
authors.forename: K Mark
authors.initials: KM
authors.lastname: Parnell
authors.forename: Shannon
authors.initials: S
authors.lastname: Merx
authors.forename: Michael V
authors.initials: MV
authors.lastname: McCullar
authors.forename: Steven B
authors.initials: SB
authors.lastname: Kanner
authors.forename: Koc-Kan
authors.initials: KK
authors.lastname: Ho
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013329:Structure-Activity Relationship; D054462:p21-Activated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D047428:Protein Kinase Inhibitors; D011744:Pyrimidinones; D054462:p21-Activated Kinases