- Discovery of thienopyrimidine-based FLT3 inhibitors from the structural modification of known IKKβ inhibitors
-
Inactivation of the NF-κB signaling pathway by inhibition of IKKβ is a well-known approach to treat inflammatory diseases such as rheumatoid arthritis and cancer. Thienopyrimidine-based analogues were designed through modification of the known IKKβ inhibitor, SPC-839, and then biologically evaluated. The resulting analogues had good inhibitory activity against both nitric oxide and TNF-α, which are well-known inflammatory responses generated by activated NF-κB. However, no inhibitory activity against IKKβ was observed with these compounds. The thienopyrimidine-based analogues were subsequently screened for a target kinase, and FLT3, which is a potential target for acute myeloid leukemia (AML), was identified. Thienopyrimidine-based FLT3 inhibitors showed good inhibition profiles against FLT3 under 1 μM. Overall, these compounds represent a promising family of inhibitors for future development of a treatment for AML.
- Park, Chun-Ho,Lee, Chulho,Yang, Jee Sun,Joe, Bo-Young,Chun, Kwangwoo,Kim, Hyuntae,Kim, Hye Yun,Kang, Jong Soon,Lee, Jangik I.,Kim, Myung-Hwa,Han, Gyoonhee
-
p. 2655 - 2660
(2014/06/09)
-
- Discovery of thienopyrimidine-based FLT3 inhibitors from the structural modification of known IKKβ inhibitors
-
Inactivation of the NF-κB signaling pathway by inhibition of IKKβ is a well-known approach to treat inflammatory diseases such as rheumatoid arthritis and cancer. Thienopyrimidine-based analogues were designed through modification of the known IKKβ inhibitor, SPC-839, and then biologically evaluated. The resulting analogues had good inhibitory activity against both nitric oxide and TNF-α, which are well-known inflammatory responses generated by activated NF-κB. However, no inhibitory activity against IKKβ was observed with these compounds. The thienopyrimidine-based analogues were subsequently screened for a target kinase, and FLT3, which is a potential target for acute myeloid leukemia (AML), was identified. Thienopyrimidine-based FLT3 inhibitors showed good inhibition profiles against FLT3 under 1 μM. Overall, these compounds represent a promising family of inhibitors for future development of a treatment for AML.
- Park, Chun-Ho,Lee, Chulho,Yang, Jee Sun,Joe, Bo-Young,Chun, Kwangwoo,Kim, Hyuntae,Kim, Hye Yun,Kang, Jong Soon,Lee, Jangik I.,Kim, Myung-Hwa,Han, Gyoonhee
-
p. 2655 - 2660
(2015/02/19)
-
- NOVEL THIENOPYRIMIDINE DERIVATIVES OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
-
The present invention relates to a novel thienopyrimidine derivative having an excellent anti? inflammatory and anti-cancer activity, or a pharmaceutically acceptable salt thereof, a process for the preparation thereof and a pharmaceutical composition comprising the same. The compound according to the present invention strongly inhibits IKB kinase-β (IKK-β) involved in the activation of a transcriptional factor, NF-κB, which is associated with inducing various immune and inflammatory diseases, whereby a composition comprising the compound is a useful therapeutic agent against inflammatory diseases, in particular, arthritis and cancer.
- -
-
-
- THIENOPYRIMIDINE DERIVATIVES AS POTASSIUM CHANNEL INHIBITORS
-
The present invention provides thienopyrimidine compounds which are potasium channels inhibitors. Pharmaceutical compositions comprising the compounds and their use in the treatment of arrhythmia are also provided.
- -
-
-