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    Multivalent ligand for myotonic dystrophy
    1.
    发明授权
    Multivalent ligand for myotonic dystrophy 有权

    公开(公告)号：US11242326B2

    公开(公告)日：2022-02-08

    申请号：US16641450

    申请日：2018-08-23

    申请人： The Board of Trustees of the University of Illinois

    发明人： Yugang Bai ,  Steven C. Zimmerman ,  Auinash Kalsotra

    IPC分类号： C07D251/64 ,  A61K9/00 ,  A61K9/06 ,  A61K9/20 ,  A61K9/48

    摘要： Abnormally long r(CUG)n repeat expansion is believed to be the major cause of Myotonic dystrophy type 1 (DM1) because it binds to muscleblind-like 1 (MBNL 1) protein which regulates RNA splicing, leading to the mis-splicing of more than 100 pre-mRNAs. The rational design of oligomers with alternating bisamidine and melamine structure resulted in good binding affinity to the RNA target because of a multivalent effect. The oligomers also showed excellent activity in disrupting nuclear foci, reversing the mis-splicing of IR minigene, and sabotaging the toxic RNA biosynthesis. Excellent activity in Drosophila based DM1 models was also observed for the oligomers, rescuing the climbing ability of the flies upon oral treatment.

    Process for the preparation of partially etherified methylolmelamines
    6.
    发明授权
    Process for the preparation of partially etherified methylolmelamines 失效
    制备部分醚化羟甲基三聚氰胺的方法

    公开(公告)号：US4408045A

    公开(公告)日：1983-10-04

    申请号：US361308

    申请日：1982-03-23

    申请人： Wilhelm Dobramysl ,  Gerhard Stern ,  Walter Raml

    发明人： Wilhelm Dobramysl ,  Gerhard Stern ,  Walter Raml

    IPC分类号： C07D251/64 ,  C07D251/70

    CPC分类号： C07D251/64

    摘要： Process for the preparation of monomeric methylolmelamine which is partially etherified with methanol or ethanol and which contains at least 4 moles of formaldehyde per mole of melamine, by reacting melamine, paraformaldehyde and methanol or ethanol in a single stage reaction, the molar ratio of melamine to formaldehyde to alcohol being 1:5 to 10:6 to 20, in a virtually anhydrous medium, under a nitrogen atmosphere, at a pH of 7 to 8 and a temperature from 50.degree. to 90.degree. C. and with a reaction time of from 3 to 30 hours.

    摘要翻译： 制备单体羟甲基三聚氰胺的方法，该单体羟甲基三聚氰胺与甲醇或乙醇部分醚化，每摩尔三聚氰胺含有至少4摩尔甲醛，通过在单阶段反应中使三聚氰胺，多聚甲醛和甲醇或乙醇反应，三聚氰胺与 甲醛至醇的比例为1:5至10：6至20，在几乎无水的介质中，在氮气氛下，pH为7至8，温度为50至90℃，反应时间为 3至30小时。

    Alkoxyalkylaminotriazine trans-etherification products
    7.
    发明授权
    Alkoxyalkylaminotriazine trans-etherification products 失效
    烷氧基烷基氨基三嗪反醚化产物

    公开(公告)号：US4393207A

    公开(公告)日：1983-07-12

    申请号：US279586

    申请日：1981-07-01

    申请人： Rainer Hummerich ,  Wolfram Weiss ,  Franz Merger ,  Guenther Immel ,  Hans-Joachim Kraus ,  Karl-Clemens Peters

    发明人： Rainer Hummerich ,  Wolfram Weiss ,  Franz Merger ,  Guenther Immel ,  Hans-Joachim Kraus ,  Karl-Clemens Peters

    IPC分类号： C07D251/18 ,  C07D251/64 ,  C08G12/42 ,  C09D161/32 ,  C07D251/70

    CPC分类号： C09D161/32 ,  C07D251/18 ,  C07D251/64 ,  C08G12/425

    摘要： Alkoxyalkylaminotriazine trans-etherification products are obtained by reacting an alkoxyalkylaminotriazine of the general formula ##STR1## where X is hydrogen, alkyl, phenyl, alkylphenyl or ##STR2## A and B are hydrogen, alkyl, alkenyl or ##STR3## and R and R' are hydrogen or alkyl, with from 0.1 to 6 moles, per mole of alkoxyalkylaminotriazine, of a .beta.-hydroxyaldehyde of the general formula ##STR4## where R", R"' and R"" are identical or different and each is hydrogen or alkyl or R"' and R"" together with the .alpha.-carbon atom form a cyclopentane or cyclohexane ring, and R"' and/or R"" can also be hydroxyalkyl and R"" can also be phenyl, in the presence of an acidic catalyst, and removing the alcohol resulting from the trans-etherification. The alkoxyalkylaminotriazine trans-etherification products may be used in baking finishes and acid-hardening surface coatings.

    摘要翻译： 烷氧基烷基氨基三嗪反醚化产物是通过使通式（I）的烷氧基​​烷基氨基三嗪（X）为氢，烷基，苯基，烷基苯基或者A，B为氢，烷基，链烯基或者R 和R'是氢或烷基，每摩尔烷氧基烷基氨基三嗪具有0.1至6摩尔的通式为“IMAGE”的β-羟基醛，其中R“，R”和R“”相同或 不同的是氢或烷基或R“和R”与α-碳原子一起形成环戊烷或环己烷环，R“和/或R”'也可以是羟烷基和 在酸性催化剂的存在下，R“也可以是苯基，并除去由反式醚化产生的醇。 烷氧基烷基氨基三嗪反醚化产物可用于烘烤整理剂和酸硬化表面涂料。

    Continuous process for manufacturing substantially fully methylated substantially fully methylolated melamine compositions
    8.
    发明授权
    Continuous process for manufacturing substantially fully methylated substantially fully methylolated melamine compositions 失效
    用于制造基本上完全甲基化的基本上完全羟甲基化的三聚氰胺组合物的连续方法

    公开(公告)号：US4293692A

    公开(公告)日：1981-10-06

    申请号：US852380

    申请日：1977-11-17

    申请人： Venkatrao K. Pai ,  Joseph F. Skrivan

    发明人： Venkatrao K. Pai ,  Joseph F. Skrivan

    IPC分类号： C08G12/00 ,  C07D251/64 ,  C08G12/30 ,  C08G12/32 ,  C07D251/70

    CPC分类号： C07D251/64

    摘要： The manufacture of a substantially fully methylated, substantially fully methylolated melamine composition is carried out by a continuous process in which the methylolation of melamine is conducted in two stages, the first stage being effected at an acidic pH and the second stage being effected at an alkaline pH. The reaction mixture is then concentrated and reacted with methanol after which all of the unreacted volatiles and precipitated salts are removed to provide the product composition.

    摘要翻译： 基本完全甲基化的，基本上完全羟甲基化的三聚氰胺组合物的制造通过连续方法进行，其中三聚氰胺的羟甲基化在两个阶段中进行，第一阶段在酸性pH下进行，第二阶段在碱性条件下进行 pH值。 然后将反应混合物浓缩并与甲醇反应，然后除去所有未反应的挥发物和沉淀的盐以提供产物组合物。