- An improved procedure for the preparation of 3-carbomethoxy-4-oxotetrahydrothiopyran, 2- and 4-carbomethoxy-3-oxotetrahydrothiophene
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An improved procedure for the preparation of the title compounds 1-3 has been developed.Direct condensation of methyl 3-mercaptopropionate with methyl acrylate using sodium hydride as a base gave compound 1 in good yield.The reaction of methyl thioglycolate and methyl acrylate at 0 degC gave compound 2 as the major product whereas at lower temperature (-40 degC) isomer 3 was found as the major product.The condensation reactions of methyl thioglycolate with methyl metacrylate and crotonate were also carried out.
- Liu, Hsing-Jang,Ngooi, Teng Ko
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Read Online
- HALOGENATED-HETEROARYL AND OTHER HETEROCYCLIC KINASE INHIBITORS, AND USES THEREOF
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The invention relates to kinase inhibitors, in particular inhibitors of protein kinases including the SIK-family CSF1R, ABL/BCR-ABL, SRC, HCK, PDGFR, KIT and/or their mutants. Although structurally similar to dasatinib, the kinase inhibitors of the invention are distinctive; possessing a particular class of halogenated heteroaryls. Such kinase inhibitors can display one or more certain properties distinct to dasatinib and other structurally similar kinase inhibitors. The kinase inhibitors of the invention or pharmaceutical compositions comprising them may be used in the treatment of a disorder or condition, such as a proliferative disorder, for example, a leukaemia or solid tumour. In particular, these and other structurally similar kinase inhibitors may be used in the treatment of a proliferative disorder - such as a mixed phenotype acute leukaemia (MPAL) - characterised by (inter-alia) the presence of MEF2C protein, a human chromosomal translocation at 11q23, and/or a KMT2A fusion oncoprotein. The kinase inhibitors or pharmaceutical compositions disclosed herein may be used topically to modulate skin pigmentation in a subject, for example to impart UV protection and reduce skin cancer risk.
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Paragraph 0598; 0636; 0640-0642
(2021/11/04)
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- The novel method to synthesis of cantharidin intermediate
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Sulfur-containing dehydrocantharidin(SD) was yielded (76% to 96%) by Diels-Alder reaction in an ionic-liquid system under ordinary pressure and temperature. We explored the influences of different ionic-liquid types, reaction temperatures, and reaction times in this reaction. We found that the optimal reaction temperature was about 35°C, the reaction time was 20 h, and the most suitable ionic liquid was 1-butyl-3-methylimidazolium tetrafluoroborate. Furthermore, in the recycling process of ionic liquid, we found that CH3CN was the most suitable extraction solvent. We explored four steps in the synthetic route to SD and achieved a good yield of 38% in total. We envisage that this process could be further developed at an industrial scale for the synthesis of Cantharidin and is destined to be an environmentally friendly way to solve the lack of cantharis as a natural resource.
- Tan, Chunbin,Liu, Xiaoling,Du, Hongfei
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p. 271 - 276
(2019/07/31)
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- SYNTHESIS OF CANTHARIDIN
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The invention provides synthetic methods for the preparation of cantharidin and analogs thereof. In one aspect, the invention provides an improved Diels-Alder cycloaddition to generate a key intermediate en route to cantharidin and analogs thereof. In certain embodiments, the new Diels-Alder reaction involves reacting Compound (2) in the presence of furan, and in the absence of acid or increased pressure, in an aprotic polar solvent with slight warming, to yield Compound (1) in favorable yield and exo-endo ratio. In another aspect, the invention also provides a new Diels-Alder reaction between compounds of Formula (III) and furan to yield compounds of Formula (IV), which can then be transformed into cantharidin or analogs thereof. In yet another aspect, the invention describes a new palladium-mediated carbonylation providing another key intermediate en route to cantharidin and analogs thereof. In addition to synthetic methods, present invention also provides compounds {i.e., intermediates) useful in the synthesis of cantharidin and analogs thereof. Compounds provided herein may have biological activity, and therefore may be used in the treatment of diseases or conditions {e.g., infectious diseases and skin conditions).
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- Development of a Practical Process for the Synthesis of PDE4 Inhibitors
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A practical, safe, and efficient process for the synthesis of PDE4 (phosphodiesterase type 4) inhibitors represented by 1 and 2 was developed and demonstrated on a multi-kilogram scale. Key aspects of the process include the regioselective synthesis of dihydrothieno[3,2-d]pyrimidine-2,4-diol 9 and the asymmetric sulfur oxidation of intermediate 11.
- Frutos, Rogelio P.,Tampone, Thomas G.,Mulder, Jason A.,Rodriguez, Sonia,Yee, Nathan K.,Yang, Bing-Shiou,Senanayake, Chris H.
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p. 982 - 988
(2016/06/09)
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- SEMICONDUCTING POLYMERS AND TERNARY BLENDS THEREOF
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Semiconducting photovoltaic polymers and compositions are disclosed. The polymers and compositions exhibit increased power conversion efficiency in solar cells and other applications.
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Paragraph 0084; 0089
(2016/08/17)
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- Scaffold Diversity Inspired by the Natural Product Evodiamine: Discovery of Highly Potent and Multitargeting Antitumor Agents
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A critical question in natural product-based drug discovery is how to translate the product into drug-like molecules with optimal pharmacological properties. The generation of natural product-inspired scaffold diversity is an effective but challenging strategy to investigate the broader chemical space and identify promising drug leads. Extending our efforts to the natural product evodiamine, a diverse library containing 11 evodiamine-inspired novel scaffolds and their derivatives were designed and synthesized. Most of them showed good to excellent antitumor activity against various human cancer cell lines. In particular, 3-chloro-10-hydroxyl thio-evodiamine (66c) showed excellent in vitro and in vivo antitumor efficacy with good tolerability and low toxicity. Antitumor mechanism and target profiling studies indicate that compound 66c is the first-in-class triple topoisomerase I/topoisomerase II/tubulin inhibitor. Overall, this study provided an effective strategy for natural product-based drug discovery. (Figure Presented).
- Wang, Shengzheng,Fang, Kun,Dong, Guoqiang,Chen, Shuqiang,Liu, Na,Miao, Zhenyuan,Yao, Jianzhong,Li, Jian,Zhang, Wannian,Sheng, Chunquan
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p. 6678 - 6696
(2015/09/07)
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- MORPHOLINO SUBSTITUTED BICYCLIC PYRIMIDINE UREA OR CARBAMATE DERIVATIVES AS MTOR INHIBITORS
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The invention relates to compounds of formula (I) wherein m, o, Ra, Rb, R1 and T1 have the meaning as cited in the description and the claims. Said compounds are useful as inhibitors of mTOR for the treatment or prophylaxis of mTOR related diseases and disorders. The invention also relates to pharmaceutical compositions including said compounds, the preparation of such compounds as well as the use as medicaments
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Page/Page column 42; 55
(2013/04/24)
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- ANTI-CANCER DRUGS AND USES RELATING THERETO FOR METASTATIC MALIGNANT MELANOMA AND OTHER CANCERS
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The present invention discloses triazene analogs of the general formula (I) and formula (II), their tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, and pharmaceutically acceptable salts thereof for the metastatic malignant melanoma and other cancers including but not limited to lymphomas, sarcomas, carcinomas, and gliomas. The invention further discloses a process for the preparation of the above said triazene analogs of formula (I) and formula (II), and their pharmaceutically acceptable compositions.
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Page/Page column 41
(2010/04/06)
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- ANTI-CANCER DRUGS AND USES RELATING THERETO FOR METASTATIC MALIGNANT MELANOMA AND OTHER CANCERS
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The present invention discloses triazene analogs of the general formula (I) and formula (II), their tautomeric forms, stereoisomers, polymorphs, hydrates, solvates, and pharmaceutically acceptable salts thereof for the metastatic malignant melanoma and other cancers including but not limited to lymphomas, sarcomas, carcinomas, and gliomas. The invention further discloses a process for the preparation of the above said triazene analogs of formula (I) and formula (II), and their pharmaceutically acceptable compositions.
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Page/Page column 17
(2010/04/23)
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- N-Hydroxyamides Omege-Substituted with Tricyclic Groups as Histone Deacetylase Inhibitors, Their Preparation and Use in Pharmaceutical Formulations
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New N-hydroxyamides of n-alkyl carboxylic acids omega substituted with suitable tricyclic systems characterised by a central 7-membered ring, having activity as inhibitors of histone deacetylase (HDAC).
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Page/Page column 9
(2008/12/08)
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- N-HYDROXYAMIDES OMEGA-SUBSTITUTED WITH TRICYCLIC GROUPS AS HISTONE DEACETYLASE INHIBITORS, THEIR PREPARATION AND USE IN PHARMACEUTICAL FORMULATIONS
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New N-hydroxyamides of n-alkyl carboxylic acids omega substituted with suitable tricyclic systems characterised by a central 7-membered ring, having activity as inhibitors of histone deacetylase (HDAC).
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Page/Page column 24-25
(2010/11/23)
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- THIENOPYRIDINONE DERIVATIVES AS MACROPHAGE MIGRATION INHIBITORY FACTOR INHIBITORS
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Inhibitors of macrophage migration inhibitory factor having a thienopyridinone backbone are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with macrophage migration inhibitory factor activity. The inhibitors of macrophage migration inhibitory factor have the following structures formula (I), (II), (III) including forms such as stereoisomers, free forms, pharmaceutically acceptable salts or esters thereof, solvates, or combinations of such forms, wherein n, R1, R2, R3, X, and Y are as defined herein. Compositions comprising an inhibitor of macrophage migration inhibitory factor in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.
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Page/Page column 56; 87-88
(2010/11/24)
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- SUBSTITUTED BENZOPYRANS AS SELECTIVE ESTROGEN RECEPTOR-BETA AGONISTS
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This invention relates to novel heterocycles which are antagonists at the melanin-concentrating hormone receptor 1 (MCHR1), also referred to as 11CBy, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in medicines. Compounds of the invention have the formula: (I)
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- Free Radical Ring-Expansion Leading to Novel Six- and Seven-Membered Heterocycles
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Free radical promoted ring-expansion of nitrogen-, oxygen- and sulfur-containing heterocyclic β-keto esters is described.Treatment of the derived phenylselenomethyl derivatives with tri-n-butyltin hydride leads to smooth one-carbon ring expansion.
- Dowd, Paul,Choi, Soo-Chang
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p. 4847 - 4860
(2007/10/02)
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- Process for preparing 2- and 4-alkoxycarbonyl thiolan-3-ones
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The invention concerns a process for preparing 2- and 4-alkoxycarbonylthiolan-3-ones useful as intermediates, which process involves cyclising a 3-akloxycarbonylmethylthiopropanoic acid ester using lithium alkoxide. Novel lithium salts are also included.
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- Esters of thienobenzopyrans and thiopyranobenzopyrans
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Novel thienobenzopyran and thiopyranobenzopyran esters represented by the formula SPC1 Wherein n is 0 to 3 and m is 0 to 3 and m + n = 2 or 3, R1 is lower alkyl, R2 is alkyl or cycloalkyl-lower alkyl, R4 is hydrogen or lower alkyl, R5 is hydrogen or lower alkyl, and R3 is EQU1 wherein Y is a straight or branched chain C1 to C8 alkylene, R6 is hydrogen or a lower alkyl, a is an integer from 1 to 4, b is an integer from 1 to 4, X is CH2, O, S or NR7 wherein R7 is hydrogen or lower alkyl, with the limitation that when X is O, S or NR7, a and b each must be 2; and the acid addition salts thereof.
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