- Discovery and optimization of a series of imidazo[4,5-b]pyrazine derivatives as highly potent and exquisitely selective inhibitors of the mesenchymal–epithelial transition factor (c-Met) protein kinase
-
Aberrant c-Met activation has been implicated in multiple tumor oncogenic processes and drug resistance. In this study, a series of imidazo[4,5-b]pyrazine derivatives was designed and synthesized, and their inhibitory activities were evaluated in vitro. Structure–activity relationship (SAR) was investigated systematically and docking analysis was performed to elucidate the binding mode, leading to the identification of the most promising compound 1D-2 which exhibited significant inhibitory effect on both enzymatic (IC50?=?1.45?nM) and cellular (IC50?=?24.7?nM in H1993 cell line) assays, as well as exquisite selectivity and satisfactory metabolic stability in human and rat liver microsomes.
- Zhao, Fei,Zhang, Jing,Zhang, Leduo,Hao, Yu,Shi, Chen,Xia, Guangxin,Yu, Jianxin,Liu, Yanjun
-
supporting information
p. 4281 - 4290
(2016/08/23)
-
- HETEROCYCLIC HYDRAZONE COMPOUNDS AND THEIR USES TO TREAT CANCER AND INFLAMMATION
-
The invention relates to compounds of formula (I) and salts thereof: wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).
- -
-
-
- HETEROCYCLIC OXIME COMPOUNDS
-
The invention relates to compounds of formula (I) and salts thereof wherein the substituents are as defined in the specification; a compound of formula (I) for use in the treatment of the human or animal body, in particular with regard to c-Met tyrosine kinase mediated diseases or conditions; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharmaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner, and processes for the preparation of a compound of formula (I).
- -
-
-
- 3-HETEROARYLMETHYL-IMIDAZO[1,2-B]PYRIDAZIN-6-YL DERIVATIVES AS C-MET TYROSINE KINASE MODULATORS
-
The invention relates to compounds of formula (I) and salts thereof, wherein the substituents are as defined in the specification, the application of a compound of formula (I) in a process for the treatment of the human or animal body, in particular with
- -
-
Page/Page column 59-60
(2011/02/24)
-
- IMIDAZO [1,2-B] PYRIDAZINE DERIVATIVES FOR THE TREATMENT OF C-MET TYROSINE KINASE MEDIATED DISEASE
-
The invention relates to compounds of formula (I) and salts thereof, formula (I) wherein the substituents are as defined in the specification, the application of a compound of formula (I) in a process for the treatment of the human or animal body, in particular with regard to C-Met tyrosine kinase mediated disease; the use of a compound of formula (I) for manufacturing a medicament for the treatment of such diseases; pharamaceutical compositions comprising a compound of the formula (I), optionally in the presence of a combination partner; processes for the preparation of a compound of formula (I).
- -
-
Page/Page column 66-67
(2009/10/21)
-