title: Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinase inhibitor with anti-tumor activity in preclinical assays.
abstract: We describe the identification of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine (3), a potent, orally active Src inhibitor with desirable PK properties, demonstrated activity in human tumor cell lines and in animal models of tumor growth.
authors.affiliation: TargeGen, Inc., 9380 Judicial Drive, San Diego, CA 92121, USA. noronha@targegen.com
authors.forename: Glenn
authors.initials: G
authors.lastname: Noronha
authors.forename: Kathy
authors.initials: K
authors.lastname: Barrett
authors.forename: Antonio
authors.initials: A
authors.lastname: Boccia
authors.forename: Tessa
authors.initials: T
authors.lastname: Brodhag
authors.forename: Jianguo
authors.initials: J
authors.lastname: Cao
authors.forename: Chun P
authors.initials: CP
authors.lastname: Chow
authors.forename: Elena
authors.initials: E
authors.lastname: Dneprovskaia
authors.forename: John
authors.initials: J
authors.lastname: Doukas
authors.forename: Richard
authors.initials: R
authors.lastname: Fine
authors.forename: Xianchang
authors.initials: X
authors.lastname: Gong
authors.forename: Colleen
authors.initials: C
authors.lastname: Gritzen
authors.forename: Hong
authors.initials: H
authors.lastname: Gu
authors.forename: Ehab
authors.initials: E
authors.lastname: Hanna
authors.forename: John D
authors.initials: JD
authors.lastname: Hood
authors.forename: Steven
authors.initials: S
authors.lastname: Hu
authors.forename: Xinshan
authors.initials: X
authors.lastname: Kang
authors.forename: Jann
authors.initials: J
authors.lastname: Key
authors.forename: Boris
authors.initials: B
authors.lastname: Klebansky
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kousba
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Lohse
authors.forename: Chi Ching
authors.initials: CC
authors.lastname: Mak
authors.forename: Andrew
authors.initials: A
authors.lastname: McPherson
authors.forename: Moorthy S S
authors.initials: MS
authors.lastname: Palanki
authors.forename: Ved P
authors.initials: VP
authors.lastname: Pathak
authors.forename: Joel
authors.initials: J
authors.lastname: Renick
authors.forename: Feng
authors.initials: F
authors.lastname: Shi
authors.forename: Richard
authors.initials: R
authors.lastname: Soll
authors.forename: Ute
authors.initials: U
authors.lastname: Splittgerber
authors.forename: Silva
authors.initials: S
authors.lastname: Stoughton
authors.forename: Suhan
authors.initials: S
authors.lastname: Tang
authors.forename: Shiyin
authors.initials: S
authors.lastname: Yee
authors.forename: Binqi
authors.initials: B
authors.lastname: Zeng
authors.forename: Ningning
authors.initials: N
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D065607:Cytochrome P-450 Enzyme Inhibitors; D004285:Dogs; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D008968:Molecular Conformation; D009368:Neoplasm Transplantation; D011485:Protein Binding; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis* / Q000494:pharmacology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
chemical_list: C522499:(7-(2,6-dichlorophenyl)-5-methylbenzo(1,2,4)triazin-3-yl)-(4-(2-pyrrolidin-1-ylethoxy)phenyl)amine; D000970:Antineoplastic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011759:Pyrrolidines; D014227:Triazines; D019061:src-Family Kinases