Synthesis And Biological Activities Of Novel Bis-heterocyclic Modified Amide/Mannich Base Derivatives

Compounds containing pyridyl unit generally have excellent biological activities,which play an important role in medicines and agricultures.Thirty-two new types of target products containing 1,2,4-triazole schiff base skeleton and introducing active groups such as pyridine were first designed and synthesized.The structures and some biological activities of the target molecules were characterized and evaluated.1?Forty new molecules were designed and synthesized for the first time through simple and efficient methods,including thirty-two two kinds of target molecules and eight important intermediates.Their structures were characterized by IR,NMR and HRMS.In the synthesis of the first series,sixteen new bis-heterocyclic amides(PTSA 1-16)were first generated using 3-(pyridin-4-yl)-1H-1?2,4-triazole-4-amino-5(4H)-thiol(PT)as starting material,which 1,2,4-triazole and 1,3,4-thiadiazole skeleton were docking through the-S-CH2-CONH-bridge,In the synthesis of the second series,sixteen new target molecules(CTM 1-16)were first synthesized by the formation of schiff-bases and Mannich reactions respectively using 3-(4-chlorophenyl)-4-amino-1H-1,2,4-triazole-5(4H)-thiol(CT)as starting material.2?The optimum reaction conditions including solvents,bases,reaction temperature and reaction time were explored in the synthesis of the first series of target molecules PTSA 1-16 The result showed that the solvent was acetone,base was K2CO3,reaction temperature was 55?,reaction time was 6 h,and the best isolated yield was up to 72.7%.3?The plant growth regulatory and herbicidal activities of thirty-two target molecules were studied by classic test methods.The results of cytokinin activity showed that the two series of the target products exhibited excellent activities,wherein CTM 5 showed the most obvious effect of promoting with the rate of up to 93.5%.In the tests of auxin activity,PTSA 12 and CTM 9 promoted better,up to 87.2%and 65.1%.In test results of herbicidal activity,the two series of target molecules were showed as level A or B,and PTSA 16 and CTM 5 had the highest rate of inhibitory,inhibition rate up to 90.7%and 87.2%.It can be seen,all of the molecules of the plant growth regulating activity and herbicidal effects are more ideal,it is expected to become excellent plant growth regulators and herbicides.4?The inhibitory activities of PTSA 1-16 and CTM 1-16 against PTP1B and Cdc25B were screened.Eighteen molecules showed excellent inhibitory activity against PTPIB,especially PTSA 15 and PTSA 12,their IC50 values were 1.19±0.22 ?g/mL,1.08 ± 0.09?g/mL respectively,which were better than the contrast oleanolic acid(IC50=1.27±0.19?g/mL).Seventeen molecules showed good the inhibitory activity against Cdc25B which the inhibition rates were above 50%.Nine compounds PTSA 4,PTSA 12,PTSA 13,PTSA 15,CTM 9,CTM 10,CTM 11,CTM 12 and CTM 15 showed better inhibitory activities,their IC50 values were 0.97±0.05 ?g/mL,1.06±0.03 ?g/mL,1.34±0.1 ?g/mL,0.94±0.11 ?g/mL,0.21 ±0.01 ?g/mL,1.01 ±0.10 ?g/mL,0.24±0.02 pg/mL,0.66±0.08 ?g/mL and 1.05±0.15 pg/mL respectively,which were lower than the reference sodium vanadate(IC50=1.86±0.24?g/mL).As a result,the target molecules are expected to be potential inhibitors of PTP1B and Cdc25B.