专利号:WO-9837078-A1 优先权日:1997-02-20 标题 :Solid phase and combinatorial synthesis of substituted thiophenes and of arrays of substituted thiophenes 发明人:DOERWALD FLORENCIO ZARAGOZA 权利人:NOVO NORDISK AS 摘要:A solid phase method for the synthesis of a plurality of differently substituted thiophenes with a wide variety of side-chain substituents as compounds of potential therapeutic interest. The thiophenes are prepared by reaction of a substrate-bound primary or secondary amine with a thiophosgene equivalent and reaction of the resulting intermediate with an acceptor-substituted acetonitrile in the presence of a base. Alkylation with an appropriate alkyl halide, followed by Thorpe-Ziegler-cyclization yields differently substituted, support-bound 3-aminothiophenes. These may be screened on the substrate or cleaved from the substrate and then screened in solution. Alternatively, the resin-bound 3-amino thiophenes or the synthetic intermediates can be subjected to further synthetic transformations (N-acylation, reduction) on the support, which permits the preparation of further therapeutically interesting compounds. The efficient synthesis of a wide variety of thiophenes using automated synthesis technology of the present method makes these compounds attractive candidates for the generation and rapid screening of diverse thiophene-based libraries. The method disclosed here provides an easy and fast access to highly diverse heterocyclic compounds of therapeutic interest, amenable to automatization.
专利号:US-6136984-A 优先权日:1996-04-22 标 题 :Solid phase and combinatorial synthesis of substituted thiophenes and of arrays of substituted thiophenes 发明人:DOERWALD FLORENCIO ZARAGOZA 权利人:NOVO NORDISK AS 摘要:A solid phase method for the synthesis of a plurality of differently substituted thiophenes with a wide variety of side-chain substituents as compounds of potential therapeutic interest is disclosed. The thiophenes are prepared by acylation of a substrate-bound primary or secondary amine with cyanoacetic acid and reaction of the resulting cyanoacetamide with an isothiocyanate in the presence of a base. Alkylation with an appropriate alkyl halide, followed by Thorpe-Ziegier-cyclization yields differently substituted, support-bound 3-aminothiophenes. These may be screened on the substrate or cleaved from the substrate and then screened in solution. Alternatively, the resin-bound 3-amino thiophenes or the synthetic intermediates can be subjected to further synthetic transformations (N-acylation, reduction) on the support, which permits the preparation of further therapeutically interesting compounds. The efficient synthesis of a wide variety of thiophenes using automated synthesis technology of the present method makes these compounds attractive candidates for the generation and rapid screening of diverse thiophene-based libraries. The method disclosed here provides an easy and fast access to highly diverse heterocyclic compounds of therapeutic interest, amenable to automatization.
专利号:US-2003172398-A1 优先权日:1999-12-21 标 题 :Novel delta-12 desaturase and methods of using it for synthesis of polyunsaturated fatty acids 发明人:BROWSE JOHN A 摘要:Desaturase enzymes, and especially animal Δ 12 -desaturases, and the use of such enzymes to alter fatty acid saturation, especially fatty acid saturation in oilseeds, are disclosed. Also disclosed are nucleic acid sequences encoding animal Δ 12 -desaturase enzymes.
专利号:US-8124838-B2 优先权日:1998-12-07 标题 :Desaturases and methods of using them for synthesis of polyunsaturated fatty acids 发明人:BROWSE JOHN A; WALLIS JAMES G; WATTS JENNIFER L 权利人:BROWSE JOHN A; WALLIS JAMES G; WATTS JENNIFER L; UNIV WASHINGTON STATE RES FDN 摘要:The amino acid and nucleic acid sequences of a Δ 5 -desaturase enzyme and a Δ 8 -desaturase enzyme are disclosed. The nucleic acid sequences can be used to design recombinant DNA constructs and vectors. These vectors can then be used to transform various organisms, including for example, plants and yeast. The transformed organisms will then produce polyunsaturated fatty acids. The amino acid sequences are useful for generating enzyme-specific antibodies that are useful for identifying the desaturases.
专利号:US-9650407-B2 优先权日:2011-11-02 标 题 :Reprogramming of cellular adhesion 发明人:GARTNER ZEV JORDAN; SELDEN NICHOLAS SCOTT; TODHUNTER MICHAEL E; LIANG SAMANTHA ISABEL; WEBER ROBERT JOSEPH; JEE NOEL YOUNGHO; LIU JENNIFER S 权利人:UNIV CALIFORNIA 摘要:Disclosed are membrane-anchored polynucleotides, and compositions comprising the membrane-anchored polynucleotides. Also disclosed are the processes for the synthesis of these compounds, compositions comprising such compounds, and the use of such compounds and compositions in research and therapeutic applications.
专利号:US-9695450-B2 优先权日:1998-12-07 标题:Desaturases and methods of using them for synthesis of polyunsaturated fatty acids 发明人:BROWSE JOHN A; WALLIS JAMES G; WATTS JENNIFER L 权利人:WASHINGTON STATE UNIV RES FOUND; UNIV WASHINGTON STATE 摘要:The amino acid and nucleic acid sequences of a Δ 5 -desaturase enzyme and a Δ 8 -desaturase enzyme are disclosed. The nucleic acid sequences can be used to design recombinant DNA constructs and vectors. These vectors can then be used to transform various organisms, including for example, plants and yeast. The transformed organisms will then produce polyunsaturated fatty acids. The amino acid sequences are useful for generating enzyme-specific antibodies that are useful for identifying the desaturases.
1: Inoue K, Ochi A, Koda A, Wako Y, Kawasako K, Doi T. The 14-day repeated dose liver micronucleus test with methapyrilene hydrochloride using young adult rats. Mutat Res Genet Toxicol Environ Mutagen. 2015 Mar;780-781:123-7. doi: 10.1016/j.mrgentox.2014.04.004. Epub 2014 Apr 24. doi: 10.1007/s00204-012-0999-8. Epub 2012 Dec 29. doi: 10.1016/j.tox.2011.10.002. Epub 2011 Oct 12. Epub 2007 Jan 17. 15: Casciano DA, Talaska G, Clive D. The potent hepatocarcinogen methapyrilene induces mutations in L5178Y mouse lymphoma cells in the apparent absence of DNA adduct formation. Mutat Res. 1991 Jun;263(2):127-32.
合成参考文献
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