Synthesis of Aryl-pyridazinone Acid and Curcumin Ester / 中国药房

OBJECTIVE:To synthesize the aryl-pyridazinone acid and curcumin ester. METHODS:With the raw material of 5-methyl-2-(3-chloro-4-fluorophenyl)-2-oxo-pyridazine acid (compound 1) and curcumin,there was ester-forming in the two sides of a phenolic hydroxyl and pyridazin-6-one carboxyl in curcumin by the catalysis of N,N-dicyclohexyl carbodiimide(DCC)/4- dimethylaminopyridine (DMAP). The targeted product,MS and NMR characterization of the structure were obtained through column chromatographic separation. Single factor was adopted to detect the effect of mixture ratio of curcumin and compound 1,re-action temperature and time and catalyst on the reactions. RESULTS:The productivity of targeted product (aryl-pyridazinone acid and curcumin ester)was 56.3%(in curcumin),the content by HPLC was 98.1%. The optimum conditions were as follows as the mixture ratio of curcumin and compound 1 was 1∶3,reaction temperature was 50 ℃,reaction time was 10 h and the catalyst was DCC/DMAP. CONCLUSIONS:The aryl-pyridazinone acid and curcumin ester is successfully synthesized with stable process.

Analgesic and anti-inflammatory activities of several 4-substituted-6-(3'-nitrophenyl)pyridazin-(2H)-3-one derivatives

Several 6-aryl-4-substituted benzylidene/furfurylidene pyridazin(2H)-3-one derivatives (4a-f) were synthesized and evaluated as analgesic and anti-inflammatory agents in mice and rats, respectively. All compounds were tested by using Eddy's hot plate and the carrageenan-induced hind paw oedema method for the evaluation of analgesic and anti-inflammatory activities, respectively. Results showed that compounds 4f, 4b, 4d, and 4e exhibited higher analgesic and anti-inflammatory activities than other remaining compounds. All title compounds (4a-f) were characterized by IR, NMR and Mass spectroscopy.

Diversos derivados benzilideno/furfurilideno piridazin(2H)-3-ona 6-aril-4-substituídos (4a-f) foram sintetizados e avaliados como analgésicos e anti-inflamatórios em camundongos e ratos, respectivamente. Todos os compostos foram testados utilizando-se o método de placa quente de Eddy e o de edema de pata induzido por carragenana para a avaliação das atividades analgésica e anti-inflamatória, respectivamente. Os resultados mostraram que os compostos 4f, 4b, 4d e 4e exibiram atividade analgésica e anti-inflamatória mais alta do que os compostos restantes. Todos os compostos (4a-f) foram caracterizados por IV, RMN e espectrometria de massas.

Bleaching of photosynthetic pigments in Chlorella protothecoides grown in the presence of SANDOZ 9785 (4-chloro-5-dimethylamino-2-phenyl-3 (2H) pyridazinone).

The unicellular green alga Chlorella protothecoides was grown in the presence of various concentrations (30–300 μΜ) of the herbicide SANDOZ 9785 (4-chloro-5-(dimethylamino)- 2-phenyl-3 (2H) pyridazinone). When the cells were grown autotrophically in the presence of the herbicide, there was a decrease in chlorophylls and carotenoids estimated on culture volume basis compared to the control. The absorption spectra of carotenes and colourless precursors extracted from photosynthetic particles showed that there was a higher carotenoid precursors/carotene ratio in the treated cells. Similarly the carotenoid precursors/xanthophyll ratio was increased by SANDOZ 9785 treatment. Chlorophyll a synthesis appeared to be inhibited more than chlorophyll b synthesis in SANDOZ 9785 treated cells resulting in a decrease in the chlorophyll a/b ratio.

Immediate effects of pyridazinone herbicides on photosynthetic electron transport in algal systems.

Pyridazinone herbicides, SANDOZ 9785 (4-chloro-5-dimethylamino2-phenyl- 3-(2H) pyridazinone), SANDOZ 9789 (4-chloro-5 (methylamino)-2-(α, α, α-trifluoro-m-tolyl- 3-(2H) pyridazinone) and SANDOZ 6706 (4-chloro-5-(methylamino)-2-(α, α, α-trifluoro-mtolyl- 3-(2H) pyridazinone) inhibited photosystem II electron transport in Chlorella protothecoides, when the herbicides were added to the assay medium. The inhibitory eficiency varied with the algal species and the nature of substitution of pyridazinones. Using 3 algal systems viz., Chlorella, Scenedesmus and Anacystis, the I50 value of for the inhibition of photosynthesis of 3 substituted pyridazinones (SANDOZ 9785, SANDOZ 6706 and SANDOZ 9789) were determined. SANDOZ 9789 was found to be the weakest inhibitor of photosystem II electron transport (H2Ο→ benzoquinone) as compared to SANDOZ 9785 and SANDOZ 6706. In general, the order of inhibition could be given as SANDOZ 6706 > SANDOZ 9785 > SANDOZ 9789. The I50 value of photosynthetic particles obtained from Chlorella cells was similar to that of whole cells, suggesting that the cell wall of Chlorella did not act as a barrier for the herbicide action. Studies on the light intensity dependence of SANDOZ 9785 inhibition of electron transport (H2O→ benzoquinone) showed that the light-dependent portion of the curve was more sensitive than the light independent portion of the curve. It is suggested that the site of action was on the reducing side of photosystem II.