The Synthesis Of Ozagrel Hydrochloride, Mercaptopurine And Dihydralazine

This paper is made up of the synthesis of Ozagrel hydrochloride, Mercaptopurine and Dihydralazine.The first part is on the synthesis of Ozagrel hydrochloride, whose chemical name is (E)-3-[4-(1H-Imidazol-1-ylmethyl)phenyl]-2-propenoic acid hydrochloride, that acts as a selective inhibitor of thromboxane A2 (TXA2). The beneficial effects of TXA2 inhibition by ozagrel include improved motor coordination after experimental stroke and antihypertensive effects in spontaneously hypertensive rats. It has been marketed in 1988 as an antithrombotic drug in Japan.A novel approach to the synthesis of ozagrel is described. The target compound is conveniently prepared from the commercially available materials, bromine and p-tolualdehyde, through the reactions of substitution, condensation and so on. The structure of the target compound was characterized by IR and'H-NMR. The preprocessing operation is simple, all materials are cheaper, less steps, mild reaction conditions and the reagents are on the less pollution to the environment, so the route is suit for the industrialization.The second part is on the synthesis of Mercaptopurine, which is a purine anti-metabolite, and it is also called 6-Mercaptopurine. It is catalyzed by hypoxanthine nucleoside pyrophosphatase (HGPRT) and changed into 6-mercaptopurine nucleotide (TIMP) in the body. It can block hypoxanthine changed into adenine nucleotides or guanine nucleotide to inhibit the synthesis of nucleic acids, and has inhibitions to many tumors special in the S-period of the cells.This paper summed up a new route that suits for industrial production through compared several formerly method:The target compound is conveniently prepared from 6-hydroxypurine as starting material through substituted reactions by chloride, sulfur, and the structure of the target compound was characterized by~1H-NMR and IR. This method has broad application prospects as it has some merits such as cheaper raw material, less steps, simple operation etc..The third part is on the synthesis of Dihydralazine, a drug for treatment the high blood pressure, which was already used in clinical trials in 70s of last century. It has the similar effects as Hydralazine, and its merit is the persistent efficacy, but there may be side-effects to restrain the application if used long-term. In recent years, medical research has revealed that Dihydralazine can be used with Reserpine and Chlorthiazide to reduce their dosage, and this way can avoid the resistance of Dihydralazine. It can also be used withβ-blocks to offset their side-effects and they have the synergistic effect on blood pressure, so it was reused in recent years.In this paper we have boldly pmproved the synthesis of Dihydralazine on the basis of the previous methods:the target compound is prepared from anhydride as starting material through aminolysis, condensation, substitution, cyclization etc., and the structre was characterized by'H-NMR and IR. It was a high-effective production route as the cheap starting material, simple steps, easy purification, high yield etc..