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    Phosphono-carboxylate compounds for treating amyloidosis
    4.
    发明申请
    Phosphono-carboxylate compounds for treating amyloidosis 审中-公开
    用于治疗淀粉样变性的膦酰羧酸盐化合物

    公开(公告)号：US20080004244A1

    公开(公告)日：2008-01-03

    申请号：US11888989

    申请日：2007-08-02

    申请人： Walter Szarek ,  Xianqi Kong ,  Gregory Thatcher ,  Boris Gorine

    发明人： Walter Szarek ,  Xianqi Kong ,  Gregory Thatcher ,  Boris Gorine

    IPC分类号： A61K31/662 ,  A61P25/00

    CPC分类号： A61K31/662 ,  A61K31/66 ,  A61K31/675

    摘要： Therapeutic compounds and methods for modulating amyloid deposition in a subject, whatever its clinical setting, are described. Amyloid deposition is modulated by the administration to a subject of an effective amount of a therapeutic compound comprising a phosphonate group and a carboxylate group, a congener thereof, or a pharmaceutically acceptable salt or ester thereof. In preferred embodiments, an interaction between an amyloidogenic protein and a basement membrane constituent is modulated.

    摘要翻译： 描述了治疗化合物和调节受试者淀粉样蛋白沉积的方法，无论其临床情况如何。 通过施用有效量的包含膦酸酯基和羧酸酯基的治疗化合物，其同类物或其药学上可接受的盐或酯来调节淀粉样蛋白沉积。 在优选的实施方案中，调节淀粉样蛋白形成蛋白质与基底膜成分之间的相互作用。

    Compositions and methods for treating amyloidosis
    6.
    发明申请
    Compositions and methods for treating amyloidosis 审中-公开
    治疗淀粉样变性的组合物和方法

    公开(公告)号：US20110281951A1

    公开(公告)日：2011-11-17

    申请号：US13066451

    申请日：2011-04-14

    申请人： Walter Szarek ,  Donald Weaver ,  Xianqi Kong ,  Heather Gordon

    发明人： Walter Szarek ,  Donald Weaver ,  Xianqi Kong ,  Heather Gordon

    IPC分类号： A61K31/185 ,  A61P3/10 ,  A61P25/00 ,  A61P25/28

    CPC分类号： A61K31/404 ,  A61K31/00 ,  A61K31/185 ,  A61K31/192 ,  A61K31/194 ,  A61K31/198 ,  A61K31/205 ,  A61K31/4015 ,  A61K31/403 ,  A61K31/4035 ,  A61K31/4152 ,  A61K31/428 ,  A61K31/437 ,  A61K31/44 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/4439 ,  A61K31/445 ,  A61K31/4453 ,  A61K31/465 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/472 ,  A61K31/4725 ,  A61K31/473 ,  A61K31/4741 ,  A61K31/675 ,  A61K31/706

    摘要： Therapeutic compounds and methods for modulating amyloid aggregation in a subject, whatever its clinical setting, are described. Amyloid aggregation is modulated by the administration to a subject of an effective amount of a therapeutic compound of the formula or a pharmaceutically acceptable salt or ester, such that modulation of amyloid aggregation occurs. R1 and R2 are each independently a hydrogen atom or a substituted or unsubstituted aliphatic or aryl group. Z and Q are each independently a carbonyl (C═O), thiocarbonyl (C═S), sulfonyl (SO2), or sulfoxide (S═O) group. “k” and “m” are 0 or 1, provided when k is 1, R1 is not a hydrogen atom, and when m is 1, R2 is not a hydrogen atom. In an embodiment, at least one of k or m must equal 1. “p” and “s” are each independently positive integers selected such that the biodistribution of the therapeutic compound for an intended target site is not prevented while maintaining activity of the therapeutic compound. T is a linking group and Y is a group of the formula -A X wherein A is an anionic group at physiological pH, and X is a cationic group.

    摘要翻译： 描述了治疗化合物和调节受试者淀粉样蛋白聚集的方法，无论其临床情况如何。 淀粉样蛋白聚集通过施用有效量的下式的治疗化合物或药学上可接受的盐或酯来调节，使得发生淀粉样蛋白聚集的调节。 R 1和R 2各自独立地为氢原子或取代或未取代的脂族基或芳基。 Z和Q各自独立地为羰基（C = O），硫代羰基（C = S），磺酰基（SO 2）或亚砜（S = O）。 当k为1时，“k”和“m”为0或1，R1不是氢原子，当m为1时，R2不为氢原子。 在一个实施方案中，k或m中的至少一个必须等​​于1.“p”和“s”各自独立地为正整数，使得治疗化合物对于预期靶位点的生物分布不被预防，同时维持治疗 复合。 T是连接基团，Y是式-AX的基团，其中A是生理pH下的阴离子基团，X是阳离子基团。

    Compositions and methods for treating amyloidosis
    7.
    发明申请
    Compositions and methods for treating amyloidosis 审中-公开
    治疗淀粉样变性的组合物和方法

    公开(公告)号：US20090099100A1

    公开(公告)日：2009-04-16

    申请号：US12217580

    申请日：2008-07-07

    申请人： Walter Szarek ,  Donald Weaver ,  Xianqi Kong ,  Heather Gordon

    发明人： Walter Szarek ,  Donald Weaver ,  Xianqi Kong ,  Heather Gordon

    IPC分类号： A61K31/185 ,  A61K31/7008 ,  A61P3/00

    CPC分类号： A61K31/404 ,  A61K31/00 ,  A61K31/185 ,  A61K31/192 ,  A61K31/194 ,  A61K31/198 ,  A61K31/205 ,  A61K31/4015 ,  A61K31/403 ,  A61K31/4035 ,  A61K31/4152 ,  A61K31/428 ,  A61K31/437 ,  A61K31/44 ,  A61K31/4409 ,  A61K31/4418 ,  A61K31/4439 ,  A61K31/445 ,  A61K31/4453 ,  A61K31/465 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/472 ,  A61K31/4725 ,  A61K31/473 ,  A61K31/4741 ,  A61K31/675 ,  A61K31/706

    摘要： Therapeutic compounds and methods for modulating amyloid aggregation in a subject, whatever its clinical setting, are described. Amyloid aggregation is modulated by the administration to a subject of an effective amount of a therapeutic compound of the formula or a pharmaceutically acceptable salt or ester, such that modulation of amyloid aggregation occurs. R1 and R2 are each independently a hydrogen atom or a substituted or unsubstituted aliphatic or aryl group. Z and Q are each independently a carbonyl (C═O), thiocarbonyl (C═S), sulfonyl (SO2), or sulfoxide (S═O) group. “k” and “m” are 0 or 1, provided when k is 1, R1 is not a hydrogen atom, and when m is 1, R2 is not a hydrogen atom. In an embodiment, at least one of k or m must equal 1. “p” and “s” are each independently positive integers selected such that the biodistribution of the therapeutic compound for an intended target site is not prevented while maintaining activity of the therapeutic compound. T is a linking group and Y is a group of the formula -A X wherein A is an anionic group at physiological pH, and X is a cationic group.

    摘要翻译： 描述了治疗化合物和调节受试者淀粉样蛋白聚集的方法，无论其临床情况如何。 淀粉样蛋白聚集通过施用有效量的下式的治疗化合物或药学上可接受的盐或酯来调节，使得发生淀粉样蛋白聚集的调节。 R 1和R 2各自独立地为氢原子或取代或未取代的脂族基或芳基。 Z和Q各自独立地为羰基（C-O），硫代羰基（C-S），磺酰基（SO2）或亚砜（S-O）基团。 当k为1时，“k”和“m”为0或1，R1不是氢原子，当m为1时，R2不为氢原子。 在一个实施方案中，k或m中的至少一个必须等​​于1.“p”和“s”各自独立地为正整数，使得治疗化合物对于预期靶位点的生物分布不被预防，同时维持治疗 复合。 T是连接基团，Y是式-AX的基团，其中A是生理pH下的阴离子基团，X是阳离子基团。

    Compounds for inhibiting diseases and preparing cells for transplantation
    8.
    发明申请
    Compounds for inhibiting diseases and preparing cells for transplantation 审中-公开
    用于抑制疾病和制备移植细胞的化合物

    公开(公告)号：US20070015737A1

    公开(公告)日：2007-01-18

    申请号：US11265537

    申请日：2005-11-02

    申请人： Anne Clark ,  Paul Fraser ,  Bruce Verchere ,  Ajay Gupta ,  David Migneault ,  Walter Szarek

    发明人： Anne Clark ,  Paul Fraser ,  Bruce Verchere ,  Ajay Gupta ,  David Migneault ,  Walter Szarek

    IPC分类号： A61K31/66 ,  G01N33/567 ,  A61K31/44 ,  A61K31/47 ,  A61K31/445 ,  A61K31/185 ,  C12N5/08 ,  A61K31/19 ,  G01N33/53

    CPC分类号： A61K31/662 ,  A61K31/00 ,  A61K31/185 ,  A61K31/194 ,  A61K31/44 ,  A61K31/47 ,  A61K31/472 ,  C07K14/4711

    摘要： Methods and compositions which are useful in the treatment of amyloidosis. In particular, methods and compositions are provided for inhibiting, preventing and treating amyloid depositions, e.g. in pancreatic islets, wherein the amyloidotic deposits are islet amyloid polypeptide (IAPP)-associated amyloid deposition or deposits. The methods of the invention involved administering to a subject a therapeutic compound which inhibits IAPP-associated amyloid deposits. Accordingly, the compositions and method of the invention are useful for inhibiting IAPP-associated amyloidosis in disorders in which such amyloid deposition occurs, such an diabetes. The invention also provides a process for the preparation of cells suitable for transplantation into a mammal, which cells are capable of forming fibrils, said process comprising contacting the cells with an inhibitor of fibril formation. In particular the process prepares cells for use in a method of treating diabetes. Also provided are a culture medium comprising the inhibitor and cells for transplantation.

    摘要翻译： 可用于治疗淀粉样变性的方法和组合物。 特别地，提供了用于抑制，预防和治疗淀粉样蛋白沉积的方法和组合物，例如。 在胰岛中，淀粉样蛋白沉积物是胰岛淀粉样蛋白多肽（IAPP）相关的淀粉样蛋白沉积或沉积物。 本发明的方法涉及向受试者施用抑制IAPP相关淀粉样沉积物的治疗化合物。 因此，本发明的组合物和方法可用于抑制发生这种淀粉样蛋白沉积的病症中的IAPP相关的淀粉样变性，如糖尿病。 本发明还提供了一种制备适于移植到哺乳动物中的细胞的方法，所述细胞能够形成原纤维，所述方法包括使细胞与原纤维形成抑制剂接触。 特别地，该方法准备细胞用于治疗糖尿病的方法。 还提供了包含抑制剂和用于移植的细胞的培养基。