Design And Synthesis Of Sinomenine N-heterocyclic Derivatives

The structure of the natural product sinomenine is similar to morphine,which is a class of drugs composed of four rings and mainly used in the treatment of rheumatoid arthritis(RA).The sinomenine used in the treatment of RA has various pharmacological activities,such as antiarrhythmia,anti-tumor,analgesia and immunomodulation.And it has been found to have better effects in the treatment of rheumatoid arthritis with 85% rate total effective.However,some side effects of sinomenine itself,such as slower duration of action and allergies,have limited the application of sinomenine in some diseases.Hence structural modification research is inevitable as a preferred means to obtain sinomenine derivatives with higher biological activity and lower side effects.In order to solve these problems,our work modified the structure of sinomenine via 1,3-dipolar cycloaddition reaction in click chemistry.The specific process is as follows:(1)The pyrazole structure was modified at the 4-OH position on the A-ring of sinomenine.Pyrazole is a five-membered N-heterocyclic ring,and its derivatives have pharmacological activities in the treatment to many kinds of diseases,such as antineoplastic,germicidal,bacteriostatic,antiphlogistic,analgesic effects,and it has become a hot research in medicinal chemistry.In this work,13 novel sinomenine derivatives were synthesized on this design route.(2)The quinoxaline substitution structure was modified at the C6 and C7 positions on C-ring of sinomenine,and then the pyrazole structure was modified at the 4-OH position on the A-ring.Quinoxaline is a six-membered benzo N-heterocyclic ring,and pyrazine it contains can be used as a synthetic hypoglycemic drug for the treatment of non-insulin-dependent(II)diabetes.Compounds containing these N-heterocyclic structures often exhibit well pharmacological activities.In this work,8 novel sinomenine derivatives were synthesized on this design route.(3)The quinoxaline substitution structure was modified at the C6 and C7 positions on C-ring of sinomenine,and then the 1,2,3-triazole structure was modified at the 4-OH position on the A-ring.The 1,2,3-triazole heterocyclic derivatives highlights its important role in many aspects,especially in medicine,it has been developed because of its well biological activity,such as germicidal and antineoplastic effects.In this work,16 novel sinomenine derivatives were synthesized on this design route.Figure [15] Table [6] Reference [80]...