- Plinabulin compound polycrystalline type and preparation method thereof
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The invention provides a plinabulin compound polycrystalline type and a preparation method thereof, and particularly relates to a polycrystalline type of (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl) methylene)piperazidine-2,5-diketone and a preparation method thereof. Three kinds of crystalline types beta, gamma and delta are developed on the basis of the crystalline type alpha of (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl) methylene)piperazidine-2,5-diketone, wherein the three kinds of crystalline types beta, gamma and delta can be prepared into monocrystallines; the three kinds of crystalline types have the advantages of clear conformation, high purity and high method repeatability; the important significance is realized on implementation of plinabulin biological effectiveness study and dosage form variety development.
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- Preparation and purification method of high-purity Plinabulin compound
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The invention provides a preparation and purification method of high-purity Plinabulin compound, which aims at mainly removing a trans-isomer. The preparation and purification method has the advantages that (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl)methylene)piperazine-2,5-diketone monohydrate and (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl)deuterated methylene)piperazine-2,5-diketone monohydrate are prepared; the purity of the prepared product is higher than 99.5%, and the content of the trans-isomer is smaller than 0.1%. The invention also relates to the preparation and purification of important intermediates, such as 5-(tert-butyl)-1H-imidazole-4-ethyl formate and 1,4-diacetylpiperazine-2,5-diketone. The preparation and purification method has the advantages that the production cost is reduced, the pos-treatment difficulty is decreased, and the technology more meets the requirements of industrialized production.
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- Acid addition salt of deuteration dehydrogenation phenyl plinabulin compound and application thereof to anti-tumor medicine preparation
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The invention discloses and provides an acid addition salt of a deuteration dehydrogenation phenyl plinabulin compound and application thereof to anti-tumor medicine preparation. The invention discloses and provides a preparation process of (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl)deuteration methylene) piperazidine-2,5-diketone compound acid addition salt. The salifying compound aims at obviously improving the solubility and the bioavailability of the active ingredients of the compound; further, the sufficient embodiment and application are achieved in aspects of curative effect and dosage form selection of the anti-tumor medicine.
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Paragraph 0036; 0037
(2017/10/31)
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- PLINABULIN PRODRUG ANALOGS AND THERAPEUTIC USES THEREOF
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Compounds of Formula (I) and (I') are disclosed, as are methods for making such compounds. Compositions and methods for treating various disease conditions including cancer and non-cancer diseases associated with vascular proliferation are also disclosed.
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- Prodrug study of plinabulin using a click strategy focused on the effects of a replaceable water-solubilizing moiety
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Plinabulin (1) is a potent anti-microtubule agent, however, its low water solubility has to be improved for the advantage in pharmacokinetics and chemotherapy. In this report, the replaceable water-solubilizing moiety of the water-soluble prodrug of plina
- Yakushiji, Fumika,Tanaka, Hironari,Muguruma, Kyohei,Iwahashi, Takahiro,Yamazaki, Yuri,Hayashi, Yoshio
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experimental part
p. 877 - 881
(2012/08/08)
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- ANALOGS OF DEHYDROPHENYLAHISTINS
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Analogs of dehydrophenylahistins are disclosed as are methods for making such compounds. Compositions and methods for treating various disease conditions including cancer and non-cancer diseases associated with vascular proliferation are also disclosed.
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- ANALOGS OF DEHYDROPHENYLAHISTINS AND THEIR THEAPEUTIC USE
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Compounds represented by the following structure (II) are disclosed: as are methods for making such compounds. Compositions and methods for treating various disease conditions including cancer and non-cancer diseases associated with vascular proliferation are also disclosed.
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