1217181-38-8Relevant articles and documents
Synthesis and in vitro screening of phenylbipyridinylpyrazole derivatives as potential antiproliferative agents
Al -Sanea, Mohammad M.,Elkamhawy, Ahmed,Zakaria, Ahmed,Park, Byung Sun,Kwon, Youngjoo,Lee, So Ha,Lee, Sang Woo,Kim, In Tae
, p. 1031 - 1045 (2015)
A series of phenylbipyridinylpyrazoles was synthesized through the reaction of 2-(4-(2-chloropyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl)acetonitrile (4) with different 6-substituted pyridine-3-ylboronic acids. The final compounds 5a-j were screened at 10 μM against over 60 tumor cell lines at the U.S. National Cancer Institute (NCI). In light of the NCI results, compounds 5c and 5h showed a broad spectrum of activity against NCI cell lines with mean growth of 53% and 58%, respectively. Compound 5e behaved differently as it showed high degree of selectivity and potency by inhibiting 96% of growth of leukemia SR cell line at 10 μM. Standard COMPARE analyses were performed at the GI 50 level and the results exhibit high correlation in the form of pairwise correlation coefficient (PCC) of more than 0.6 between three of the current compounds and three standard known anticancer agents. Compound 5e demonstrated high correlation levels with merbarone (NSC S336628) with a PCC value of 0.631. Compound 5h showed a considerably high PCC value of 0.626 with dichloroallyl lawsone, while compound 5i, showed PCC values of 0.601 and 0.604 with both dichloroallyl lawsone and N,N-dibenzyldaunomycin (NSC S268242), respectively. These three standard agents have anticancer activity via two major mechanism of actions, inhibition of topoisomerase II and inhibition of biosynthesis of pyrimidine nucleotides, therefore, compounds 5a-j are promising therapeutic agents for targeting different human malignancies. Prediction of drug-likeness and toxicity of these newly synthesized derivatives were also considered.
Design and synthesis of novel phenylaminopyrimidines with antiproliferative activity against colorectal cancer
Henidi, Hanan A.,Al-Abd, Ahmed M.,Al-Abbasi, Fahad A.,Binmahfouz, Hawazen A.,El-Deeb, Ibrahim M.
, p. 21578 - 21586 (2019)
New phenylaminopyrimidine (PAP) derivatives have been designed and synthesised as potential tyrosine kinase inhibitors for the treatment of cancer. The synthesized compounds share a general structure and vary in the substitution pattern at position-2 of t
PYRAZOLE COMPOUNDS WITH INHIBITORY ACTIVITY AGAINST ROS KINASE
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, (2011/02/18)
Disclosed herein are novel pyrazole compounds, pharmaceutically acceptable salts thereof, a method for preparing the same, and uses thereof as anticancer agents.
Design and synthesis of new potent anticancer pyrazoles with high FLT3 kinase inhibitory selectivity
El-Deeb, Ibrahim Mustafa,Lee, So Ha
experimental part, p. 3961 - 3973 (2010/08/06)
A new series of 1H- and 2H-pyrazole derivatives (35 final compounds) has been designed and synthesized in this study. A selected group (13 compounds) was then tested over a panel of 60 cancer cell lines at a single dose concentration of 10 μM. At this concentration, six compounds have showed moderate to strong mean inhibitions, and were further tested at five-dose testing mode to determine their IC50 over the 60 cell lines. The IC50 values of the tested compounds indicated high potency (as for compound 10f) as well as high efficacy (as for compound 11e). Accordingly, compound 10f was then tested at a single dose concentration of 10 μM over a panel of 54 kinases to determine its kinase inhibitory profile. The compound has showed good selectivity towards FLT3 kinase, associated with a moderate potency, with an IC50 value of 1.74 μM.
Design, synthesis, screening, and molecular modeling study of a new series of ROS1 receptor tyrosine kinase inhibitors
El-Deeb, Ibrahim M.,Park, Byung Sun,Jung, Su Jin,Yoo, Kyung Ho,Oh, Chang-Hyun,Cho, Seung Joo,Han, Dong Keun,Lee, Jae Yeol,Lee, So Ha
scheme or table, p. 5622 - 5626 (2010/04/30)
A series of rationally designed ROS1 tyrosine kinase inhibitors was synthesized and screened. Compound 12b has showed good potency with IC50 value of 209 nM, which is comparable with that of the reference lead compound 1. Molecular modeling studies have been performed, that is, a homology model for ROS1 was built, and the screened inhibitors were docked into its major identified binding site. The docked poses along with the activity data have revealed a group of the essential features for activity. Overall, simplification of the lead compound 1 into compound 12b has maintained the activity, while facilitated the synthetic advantages. A molecular interaction model for ROS1 kinase and inhibitors has been proposed.
