title: Synthesis and SAR of 4-(3-hydroxyphenylamino)pyrrolo[2,1-f][1,2,4]triazine based VEGFR-2 kinase inhibitors.
abstract: A versatile synthesis of the suitably functionalized pyrrolo[2,1-f][1,2,4]triazine nucleus is described. SAR at the C-5 and C-6 positions of the 4-(3-hydroxy-4-methylphenylamino)pyrrolo[2,1-f][1,2,4]triazine template led to compounds with good in vitro potency against VEGFR-2 kinase. Glucuronidation of the phenol group is mitigated by incorporation of a basic amino group on the C-6 side chain of the pyrrolotriazine nucleus.
authors.affiliation: Department of Oncology Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Borzilleri
authors.forename: Zhen-Wei
authors.initials: ZW
authors.lastname: Cai
authors.forename: Christopher
authors.initials: C
authors.lastname: Ellis
authors.forename: Joseph
authors.initials: J
authors.lastname: Fargnoli
authors.forename: Aberra
authors.initials: A
authors.lastname: Fura
authors.forename: Tracy
authors.initials: T
authors.lastname: Gerhardt
authors.forename: Bindu
authors.initials: B
authors.lastname: Goyal
authors.forename: John T
authors.initials: JT
authors.lastname: Hunt
authors.forename: Steven
authors.initials: S
authors.lastname: Mortillo
authors.forename: Ligang
authors.initials: L
authors.lastname: Qian
authors.forename: John
authors.initials: J
authors.lastname: Tokarski
authors.forename: Viral
authors.initials: V
authors.lastname: Vyas
authors.forename: Barri
authors.initials: B
authors.lastname: Wautlet
authors.forename: Xioping
authors.initials: X
authors.lastname: Zheng
authors.forename: Rajeev S
authors.initials: RS
authors.lastname: Bhide
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D014227:Triazines; D040301:Vascular Endothelial Growth Factor Receptor-2