- Preparation method of apremilast impurity
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The invention discloses a preparation method of an apremilast impurity, and belongs to the technical field of apremilast impurity synthesis, the method comprises the following steps: taking 3-halogenated-2-methyl benzoic acid as a starting raw material to prepare an intermediate M1 through oxidation reaction, and performing dehydration condensation on the intermediate M1 to prepare an intermediate M2; taking 3, 4-dihydroxybenzonitrile as an initial raw material, carrying out an oxygen methylation reaction to prepare an intermediate M3, sequentially carrying out nucleophilic addition, a reduction reaction and alkaline hydrolysis on the intermediate M3 to prepare an intermediate M4, carrying out an amide exchange reaction on the intermediate M2 and the intermediate M4 to prepare an intermediate M5, and carrying out a coupling reaction and acid treatment on the intermediate M5 to obtain a target product. The method has the characteristics of reasonable synthetic route, easily available raw materials, simple and easy operation, high yield and high purity, and the prepared apremilast impurity can be used as a reference substance for qualitative and quantitative research of impurities in apremilast quality research, controls the content of related substances in bulk drugs, and ensures the quality of the bulk drugs.
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Paragraph 0031-0035
(2021/06/02)
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- FUSED-GLUTARIMIDE CRBN LIGANDS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same. The present invention also relates to compounds and methods useful for binding and modulating the activity of cereblon (CRBN), especially for the inhibition of CRBN, and the treatment of CRBN-mediated disorders.
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Paragraph 00384
(2021/02/12)
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- HETEROCYCLIC DERIVATIVES
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Compounds of the formula (I): Q1-Q2-Q3, in which Q1, Q2 and Q3 have the meanings indicated in Claim 1, degrade target proteins, and can be employed, inter alia, for the treatment of diseases such as cancer, multiple sclerosis, cardiovascular diseases, central nervous system injury and different forms of inflammation.
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Page/Page column 52; 88-89
(2020/08/13)
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- BIFUNCTIONAL COMPOUNDS FOR DEGRADING BTK VIA UBIQUITIN PROTEOSOME PATHWAY
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The present invention relates to compounds useful for degrading BTK via a ubiquitin proteolytic pathway. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
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- Enhanced fluorescence of phthalimide compounds induced by the incorporation of electron-donating alicyclic amino groups
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Due to their high thermal and environmental stability, polyimides (PIs) are one of the most attractive candidates for novel highly fluorescent polymers, though photophysical studies of PIs are challenging owing to their poor solubility in common solvents. To overcome these problems, we have synthesized and examined a series of low molecular weight model imide compounds: substituted N-cyclohexylphthalimides with alicyclic amino groups at the 3 or 4-positions of the benzene rings (x-NHPIs). Their photophysical properties were systematically investigated by steady-state UV/Visible absorption, fluorescence, and time-resolved fluorescence techniques. In solution, unsubstituted N-cyclohexylphthalimide (NHPI) showed almost no emission, while x-NHPIs exhibited enhanced fluorescence emission depending on the solvent polarity. Analysis of the solvatochromism of the x-NHPIs via Lippert-Mataga plots indicated the generation of large dipole moments in the excited singlet states originating from the intramolecular charge-transfer (ICT) states. The significant difference in the fluorescence quantum yields (Φ) between the 3-substituted (3Pi and 3Pyr) and 4-substituted NHPIs (4Pi and 4Pyr) strongly suggests that the former form a twisted ICT (TICT) state, whereas the latter form a planar ICT (PICT) state when excited. 4-Substituted NHPIs also show high fluorescence yields in the crystalline state. A particularly large Φ value was obtained for the 4Pi crystal, which we explain by the large intermolecular distances and the arrangement of molecules minimizing intermolecular interactions as well as the small non-radiative deactivation rate. These facts clearly demonstrate that the introduction of an alicyclic amino group into NHPI at the 4-position enhances the fluorescence quantum yields significantly, which suggests a new pathway for the development of novel, highly fluorescent PIs.
- Orita, Ryoji,Franckevi?ius, Marius,Vy?niauskas, Aurimas,Gulbinas, Vidmantas,Sugiyama, Haruki,Uekusa, Hidehiro,Kanosue, Kenta,Ishige, Ryohei,Ando, Shinji
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p. 16033 - 16044
(2018/06/20)
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- NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A
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The present invention relates to novel carboxamide compounds, pharmaceutical compositions containing them, and their use in therapy. The compounds possess valuable therapeutic properties and are particularly suitable for treating or controlling medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders
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- Synthesis and biological activity of n-butylphthalide derivatives
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A series of n-butylphthalide derivatives were designed and synthesized. The in vitro activities of these compounds were evaluated by a resting tension of isolated rat thoracic aorta ring assay. Compounds 4g and 4i were found to be more active than n-butylphthalide.
- Wang, Wei,Cha, Xue-Xiang,Reiner, John,Gao, Yuan,Qiao, Hai-Ling,Shen, Jia-Xiang,Chang, Jun-Biao
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experimental part
p. 1941 - 1946
(2010/06/19)
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- Isoindole-imide compounds and compositions comprising and methods of using the same
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This invention relates to isoindole-imide compounds, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.
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Page/Page column 70
(2010/11/26)
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- On the regioselectivity of metal hydride reductions of 3-substituted phthalic anhydrides
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A problem of 3-methoxyphthalide reduction by metal hydrides was reinvestigated. Various effects controlling selectivity of reductions in 3-substituted phthalides were studied, and a qualitative interpretation of the results is now proposed. Methods for obtaining enhanced yields of one or the other lactonic product were developed.
- Soucy,Favreau,Kayser
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p. 129 - 134
(2007/10/02)
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