Synthesis and biological evaluation of pyrrolopyridazine derivatives as novel HER-2 tyrosine kinase inhibitors.
A series of novel pyrrolopyridazine derivatives have been discovered to be HER-2 inhibitors. These compounds selectively inhibited HER-2 kinase activity at low nanomolar concentrations. Compound 7d was identified as a potent HER-2 inhibitor with an IC(50) of 4 nM.
Tang
Peng Cho
PC
Shanghai Hengrui Pharmaceuticals Co., Ltd., 279 Wenjing Road, Shanghai 200245, China. tangpc@shhrp.com
Feng
Jun
J
Huang
Li
L
Xu
Zhe
Z
Cheng
Ling
L
Zhang
Xu
X
Zhang
Lei
L
Hu
Bing
B
D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D008958:Models, Molecular; D011724:Pyridazines / Q000138:chemical synthesis / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D053634:TYK2 Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D011724:Pyridazines; D011758:Pyrroles; C508945:Pyrrolopyridazine; D053634:TYK2 Kinase