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.
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.
Noronha
Glenn
G
TargeGen, Inc., 9380 Judicial Drive, San Diego, CA 92121, USA. noronha@targegen.com
Barrett
Kathy
K
Boccia
Antonio
A
Brodhag
Tessa
T
Cao
Jianguo
J
Chow
Chun P
CP
Dneprovskaia
Elena
E
Doukas
John
J
Fine
Richard
R
Gong
Xianchang
X
Gritzen
Colleen
C
Gu
Hong
H
Hanna
Ehab
E
Hood
John D
JD
Hu
Steven
S
Kang
Xinshan
X
Key
Jann
J
Klebansky
Boris
B
Kousba
Ahmed
A
Li
Ge
G
Lohse
Dan
D
Mak
Chi Ching
CC
McPherson
Andrew
A
Palanki
Moorthy S S
MS
Pathak
Ved P
VP
Renick
Joel
J
Shi
Feng
F
Soll
Richard
R
Splittgerber
Ute
U
Stoughton
Silva
S
Tang
Suhan
S
Yee
Shiyin
S
Zeng
Binqi
B
Zhao
Ningning
N
Zhu
Hong
H
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*
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