The Design And Synthesis Of Amino-aiyl Compounds And Their Preliminary Study Related To Anti-tumor Activity

Chronic myeloid leukemia （CML） was the first malignant tumors to have fixedcytogenetic abnormalities, the current study agreed that the abnormally high levels ofthe activity of Bcr-Abl protein tyrosine is the main reason leading to CML. Tyrosinekinase inhibitors （TPKI） applied CML therapy research deepened. Currently researchabout multi-target receptor tyrosine kinase inhibitors is very active, there are somenew drugs, and some have made significant breakthrough, opens the door of hope forcancer treatment, such as, Bcr-Abl kinase small molecule inhibitors imatinib. In thispaper, I have been analysised the structure of small molecule protein tyrosine kinaseinhibitor such as dasatinib, in order to put forword arylamino group as apharmacophore, connectioning hydroxyproline as a carrier group, designed andsynthesized a series of new compounds, analysis structural characterization andevaluate their anti-k562cell activity and found three leading compounds with certainactivity for further research foundation. This paper mainly includes the followingaspects of the research:1. The synthesis of phosphoric acid two isopropyl ester substituted L-hydroxyproline: with sodium hypochlorite and phosphoric acid two isopropyl esterreaction, chlorine substitut on hydrogen phosphate, increased electropositivephosphorus atoms and react nucleophilic reactions with L-hydroxyproline, adjustingpH value with sodium hydroxide, this paper adopts the one-pot synthesis, the yield ofaround54%.2. The synthesis of heterocyclic thiazole: the reaction of NBS with ethylacetoacetate into bromo ethyl acetoacetate, and then reacts with thiourea to producethiazole.3. The synthesis of amide bond: phosphoric acid two isopropyl ester substitutedL-hydroxyproline and some amino aromatic, heteroaromatic bond together throughamino amide, with DCC as dehydrating agent, reacting to obtain the final product atnormal atmospheric temperature. 4. We evaluate ten new synthetic compounds activation through the MTTmethod, active research evaluate ten compounds’ killing effect on K562cells in the10^-5mol/L、（1/2）×10^-5mol/L、（1/2）²Ã—10^-5mol/L、（1/2）³Ã—10^-5mol/L vitroconcentration.Nine new compounds were synthesized. Several new compounds was foundwith activity in preliminary research. Further research activities are underway.