- Isolation, synthesis, and cytotoxicity evaluation of two impurities in nomegestrol acetate
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Nomegestrol acetate (NOMAc) is a synthetic progesterone analog and classified as a fourth-generation progestin. It has been approved in many countries for oral contraception, hormonal replacement therapy (HRT), and treatment of various gynecological disorders. There are several synthetic routes reported for the synthesis of NOMAc and they all share the very similar last three to five steps toward the conversion of 6-methylene to 6-methyl-6,7-unsaturated structure. Therefore the final product from different processing routes may have similar impurity profiles. In the analysis of NOMAc, we identified two impurities, impurity A (listed in EP 8.0) and impurity B (not specified in EP 8.0). Both impurities were further confirmed by synthesis. In addition, both impurities and NOMAc were evaluated for their in vitro cytotoxicities against L02 liver cells, mesenchymal stem cells, MCF-7 breast cancer cells, and C33A cervical cancer cells. These three analogs are not cytotoxic to the four cell lines at low concentrations (20 μM). NOMAc and impurity A showed cytotoxicity to L02, MCF-7, and C33A cells at high concentrations, while impurity B did not show significant cytotoxicity to any of the cell lines tested.
- Xie, Bao-Cheng,Song, Shu-Yong,Xie, Xiao-Yang,Sun, Yu-Tong,Zhang, Xiao-Yuan,Xu, Dao-Hua,Huang, Yun-Sheng
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- Synthesis method of 6 alpha-methyl-17 alpha-acetoxyl-19- methylestra-4-en-3,20-dione
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The invention provides a synthesis method of 6 alpha-methyl-17 alpha-acetoxyl-19-methylestra-4-en-3,20-dione. The synthesis method comprises the following steps: 1, adding palladium/carbon into ethanol-water-cyclohexene, stirring and heating to be reflux; and 2, adding NO MAc into a palladium/carbon- ethanol-water-cyclohexene mixed solution in the step 1, heating to 75-85DEG C, immediately filtering after the reaction is finished, cooling and crystalizing to obtain a 6alpha-methyl-17alpha-acetoxyl-19- methylestra-4-en-3,20-dione crude product, and furthering purifying to obtain the product with the purity of 99.5. The invention provides a bran-new preparation method of 6 alpha-methyl-17 alpha-acetoxyl-19-methylestra-4-en-3,20-dione. The synthesis technology is simple, the cost is low, the operation is simple and convenient, the conversion rate is up to 89%, the yield is up to 71%, and the purity of the product is 99.5%.
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Paragraph 0011-0014
(2017/08/29)
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- New substituted 19-nor-pregnane derivatives
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The invention relates to compounds of the formula : wherein : each of R1and R2is hydrogen or a (C1-C6)alkyl, R1and R2being not simultaneously hydrogen ; R3is hydrogen, a (C1-C6)alkyl or a (C1-C6)alkoxy ; R4is hydrogen, a (C1-C6)alkyl or a group -COR6where R6is a (C1-C6)alkyl ; R5is hydrogen or a (C1-C6)alkyl ; n is zero or one ; X is oxygen or an hydroxyimino group ; and the dotted line may represent a double bond ; provided that when n = 0, R3is hydrogen only if both R1and R2are a (C1-C6)alkyl, and to pharmaceutical compositions containing them. These compounds are potent progestogens which are devoid of residual androgenic activity.
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