Anticancer Drugs Music Neanderthal Synthesis And Characterization

As a serious disease of human being, the incidence of tumor and its death rate present an ascending trend in our country. The death rate of malignancy is only inferior to that of heart-brain blood vessel ailment, which has the highest death rate among all the diseases. With complicated carcinogenesis mechanism, the incidence of tumor and its development are synthetically caused by many factors, and many malignancies cannot be healed by current therapies. The traditional therapies are known as surgery, radiotherapy and chemotherapy. Many new therapies appear with development of molecular biology and immunology, such as gene and immunologic therapies. However, all these therapies cannot provide an effective remedy to all kinds of tumors. Therefore, it's a pressing task to develop new tumor therapies.Lonidamine(LND) or 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid, a dichlorobenzene derivative of indazole acid, is a kind of heat-sensitivity anticancer drug. LND is effective against a number of tumors, including head-neck cancer, lung cancer, chronic lymphoblastic leukemia, malignant melanoma, breast cancer, encephaloma, and so on.In this paper, 2-Hydroxyimino-N-phenyl-acetamide was prepared by using aniline as starting material, which reacted with chloral hydrate, hydroxylamine hydrochloride in sodium sulfate solution. Through experiments, the yield (92.6%) was achieved under optimal reaction conditions: mole ratio of aniline, hydroxylamine hydrochloride and chloral hydrate 1:3:1.3, reaction temperature 98℃, reaction time 20 min. Then, the product was characterized by element analysis, IR, UV, ~1HNMR.In addition, after Beckmann rearrangement and cyclizing, the product of 2-Hydroxyimino-N-phenyl-acetamide reacted with sulfuric acid to synthesize 1H-indazole-3-carboxylic acid. In diazotization, the yield was improved from 51.2% to 82.3% through replacing stannous chloride by sodium dithionate. The purification of product can be implemented easily. Meanwhile, the structure of the product was confirmed by element analysis, IR, UV, and ~1HNMR. In conclusion, lonidamine was synthesized through the nucleophilic substitution of 1H-indazole-3-carboxylic acid by 2,4-dichloro-1-chloromethyl-benzene. When potassium iodide was used as catalyst under nitrogen, the yield was improved from 87.5% to 89.5%. The optimal reaction condition was found to be mole ratio of lH-indazole-3-carboxylic acid and 2,4-dichloro-1-chloromethyl-benzene 1:1.3, temperature 95℃and time 4h. Finally, the structure of lonidamine was identified by element analysis, IR, UV, and ~1HNMR.