Synthesis Of Theanalogs Of Antileukemia Drug Pipobroman

Tumor is a common and frequently-occurring disease which has become a serious threat to human life,it is also one of the major ills which may affect people's quality of life, the mortality rate is second only to the cardiovascular disease in second place. Currently, the treatment of the tumor depend on the development of antitumor drugs. In the last decades, although some new antitumor drugs had been discovered,due to the vague idea of the antitumor mechanism, it is blind to find more effective drugs. Therefore, in order to get the new targeted antitumor drugs, it is necessary to modify and transform the structures of previous drugs, expecting to gain new drugs which have lower toxicity and better antitumor activities. Piperazine derivatives have a wide range of biological activities, there has been no less than one hundred species of clinical drugs which contain piperazine structure. So design and synthesis of piperazine derivatives is important to find a new direction in the exploitation of antitumor drugs. The piperazine compounds are composed of simple piperazine derivatives, dipiperazine diquaternary ammonium derivatives and dispirotripiperazine derivatives. Pipobroman is the representative of the first one. Pipobroman is widely used in the treatment of leukemia, particularly in the treatment of the chronic myeloid leukemia which is resistant to conventional therapy. It has been eliminated from the market due to its high toxicity which is mainly the depression of bone-marrow function.Selecting pipobroman as the leading compound, a series of piperazine derivatives were synthesized in the principle of hybridization. They include two kinds of piperazine derivatives that are symmetrical and unsymmetrical derivatives. The typical new compounds include 1,4-bis[3-(aminodithiocarboxy)propionyl]piperazine, 1,4-bis[3-(nitrooxy)propionyl]piperazine, 1,4-bis[3-(phthalimido)propionyl]piperazi -ne, 1-(4-methylbenzenesulfonyl)-4-(3-bromopropionyl)piperazine, 1-(4-methoxyph -enyl)-4-(3-bromopropionyl)piperazine, 1-benzhydryl–4-(3-bromopropionyl)piperazi -ne. They have not been found in the literature and most of their structures were confirmed by 1H-NMR and infrared spectrum.