Tu, Yuanbiao published the artcileDesign, synthesis, and docking studies of afatinib analogs bearing cinnamamide moiety as potent EGFR inhibitors, Safety of (E)-3-(2,4-Dimethoxyphenyl)acrylic acid, the publication is Bioorganic & Medicinal Chemistry (2016), 24(7), 1495-1503, database is CAplus and MEDLINE.
Two series of afatinib derivatives bearing cinnamamide moiety (10a-n and 11a-h) were designed, synthesized and evaluated for the IC50 values against four cancer cell lines (A549, PC-3, MCF-7 and Hela). Two selected compounds (10e, 10k) were further evaluated for the inhibitory activity against EGFR and VEGFR2/KDR kinases. Seven of the compounds showed excellent cytotoxicity activity and selectivity with the IC50 values in single-digit ¦ÌM to nanomole range. Three of them are equal to more active than pos. control afatinib against one or more cell lines. The most promising compound 10k showed the best activity against A549, PC-3, MCF-7 and Hela cancer cell lines and EGFR kinase, with the IC50 values of 0.07 ¡À 0.02 ¦ÌM, 7.67 ¡À 0.97 ¦ÌM, 4.65 ¡À 0.90 ¦ÌM and 4.83 ¡À 1.28 ¦ÌM, which were equal to more active than afatinib (0.05 ¡À 0.01 ¦ÌM, 4.1 ¡À 2.47 ¦ÌM, 5.83 ¡À 1.89 ¦ÌM and 6.81 ¡À 1.77 ¦ÌM), resp. Activity of compounds 10e (IC50 9.1 nM) and 10k (IC50 3.6 nM) against EGFR kinase were equal to the reference compound afatinib (IC50 1.6 nM). Structure-activity relationships (SARs) and docking studies indicated that replacement of the aqueous solubility 4-(dimethylamino)but-2-enamide group by cinnamamide moiety didn’t decrease the antitumor activity. The results suggested that methoxy substitution had a significant impact on the activity and methoxy substituted on C-4 or C-2,3,4 position was benefit for the activity.
Bioorganic & Medicinal Chemistry published new progress about 16909-09-4. 16909-09-4 belongs to catalysis-chemistry, auxiliary class Alkenyl,Carboxylic acid,Benzene,Ether, name is (E)-3-(2,4-Dimethoxyphenyl)acrylic acid, and the molecular formula is C14H26O2, Safety of (E)-3-(2,4-Dimethoxyphenyl)acrylic acid.
Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia