| The drug of benzylprimidines is scarce and aged in China. The existing drugs have short eliraented half life or low bioavailability or narrow clinical use. In order to change this state and increase the utility of benzylprimidine drug in veterinary medicine, and search for better veterinary drugs, the study on the synthesis of aditoprim(ADP) was carried out. The target product was synthesized by bromination, methoxylation, methyl-methylesterlation, methyl sulfonylation, reduction, condensation, cyclization seven steps. The material in the step of condensation which is bought in difficult in the market was synthesized by ourselves.The process to the synthesis of ADP and the material is:(1) Bromination. 4-Amino-3, 5-dibromo benzoic acid (I) was obtained by bromination from initial material para-aminobenzoic acid. Melting point (m. p. ) 325℃.(2) Methoxylation. I was treated with sodium methylate and the correspond catalyst copper(I) chloride to obtained 4-amino-3, 5-dimethoxy benzoic acid(II). m. p. 204℃.(3) Methyl-methylesterlation. II was stirred with dimethylsulfate under the catalyst of absolute pottasum carbonate and then obtained 4-dimethylamino-3, 5-dimethoxy benzoic acid methyl ester (III), m. p. 70~71℃.(4) Methylsulfonylation. Ill was reacted with sodium hydride and dimethylsulfone in dimethylsulfoxide, then 4-dimethylamino-3, 5-dimethoxy-alpha -[(methyl-sulfonyl)-methyl]-benzyl acetophenone(IV) was obtained, m. p. 108 ?nor(5) Reduction. IV was reducted by sodium borohybrid in the presence of ethanol, Which was obtained 4-dimethylamino-3, 5-dimethoxy-a-[(methylsulf-fonyl-methylj-benzyl alcohol(V). m. p. 148-150℃(6) Condensation. V was condensed with P -aniline-propionitrile in the solvent of dimethylsulfoxide and afforded 4-dimethylamino-3, 5-dimethoxy-hydrocinnamicacid. (VI). m. p. 169~170℃(7) Cyclization. Under the treating of sodium ethalate, VI was cyclizated with guanidine carbonate and was obtained aditoprim(ADP). m. p. 49~50癈(8) The material of 6th step 3- aniline-propionitrile was obtained by mixing acrylonitrile with aniline under the catalyst of zinc chloride.The yield of the above reaction was 92%, 88%, 50%, 84%, 90%, 30%, 30%, 92% respectively. The intermediate products and the material was identified by 1H-Nuclear Magenetic Reasonace (1H-NMR) or Mass Spectrum(MS). The target product was identified by 1H-Nuclear Magenetic Reasonace ('H-NMR), 13C-Nuclear Magenetic Reasonace (13C-.VMRK Mass Spectrum (MS), Ultraviolet Spectra(UV), Infrared Spectra(IR). The intermediate III is a novel sunscreen. It has a potent prospect in the commodity industry and pharmaceutical industry. ADP has a long elimination half-life and high bioavailability, it can be used in many species of animal.After ADP was synthesized, its antibacterial activity to E. coli(C83828), salmonella cholerasuis(isolating from clinical), streptococcus (isolating from clinical), staphylococcus aureus (65003), pasteurella multocida (isolating from clinical), staphylococcus aureus (isolating from clinical) was measured by tube dilution method. The minimal inhibitory concentration of ADP was 5 μg/ml to 20μg/ml, whereas the contrast group of TMP was 20μ g/ml to 80μg/ml. The minimal bactericidal concentration of ADP to above six bacterial was 320μg/ml to 1280μg/ml, While the contrast group of TMP to E. coli(C83828), pasteurella multocida (isolating from clinical) staphylococcus aureus (65003) was 1280 V- g/ml, to other three strains ofbacterial was >1280μg/ml.The result indicated the in vitro antibacterial activity of ADP was superior to TMP. In combination with the reference of foreign, its in vivo activity would be more superior to IMP. Therefore it is worth to be further research and developing.It is concluded that the benzylprimidine drug ADP used exclusively for animals was firstly synthesized in China. This changed the state of scarce and aged in this varity. The key intermediate 4-dimethylamino-3, 5-dimethoxy benzoic acid methyl ester was a novel sunscreen, it was al...
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