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    Methimazole derivatives and tautomeric cyclic thiones to inhibit cell adhesion
    1.
    发明申请
    Methimazole derivatives and tautomeric cyclic thiones to inhibit cell adhesion 审中-公开
    甲基咪唑衍生物和互变异构环状硫堇以抑制细胞粘附

    公开(公告)号：US20050209295A1

    公开(公告)日：2005-09-22

    申请号：US10801986

    申请日：2004-03-16

    申请人： Leonard Kohn ,  Douglas Goetz ,  Norikazu Hari ,  Chris Lewis ,  Cesidio Giuliani ,  Giorgio Napolitano ,  Nilesh Dagia

    发明人： Leonard Kohn ,  Douglas Goetz ,  Norikazu Hari ,  Chris Lewis ,  Cesidio Giuliani ,  Giorgio Napolitano ,  Nilesh Dagia

    IPC分类号： A61K31/4166

    CPC分类号： A61K31/4166 ,  Y02A50/411

    摘要： The present invention relates to novel compounds and methods of use for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. In particular, methimazole derivatives and tautomeric cyclic thiones have the ability to inhibit the adhesion and the migration of leukocytes. In addition to being active anti-inflammatories, the methimazole derivatives and tautomeric cyclic thiones and their physiologically tolerable salts, derivatives and prodrugs are generally suitable for the treatment (i.e., for the therapy and prophylaxis) of diseases that are based on the interaction between VCAM-1 and its ligands or can be influenced by an inhibition of this interaction. In particular, the methimazole derivatives and tautomeric cyclic thiones are suitable for the treatment of diseases that are caused at least partly by an undesired extent of leukocyte adhesion and/or leukocyte migration or are connected therewith, and for whose prevention, alleviation or cure the adhesion and/or migration of leukocytes should be decreased.

    摘要翻译： 本发明涉及新型化合物和用于抑制和预防细胞粘附和细胞粘附介导的病理学的方法。 本发明还涉及包含这些化合物的药物制剂及其用于抑制和预防细胞粘附和细胞粘附介导的病理学的方法。 本发明的化合物和药物组合物可用作治疗剂或预防剂。 特别地，甲巯咪唑衍生物和互变异构环状硫堇具有抑制白细胞粘附和迁移的能力。 除了是主要的抗炎药之外，甲巯咪唑衍生物和互变异构环状硫堇及其生理上可耐受的盐，衍生物和前药通常适用于基于VCAM相互作用的疾病的治疗（即治疗和预防） -1及其配体或可能受到这种相互作用的抑制的影响。 特别地，甲巯咪唑衍生物和互变异构环状硫堇适用于治疗至少部分由不期望的白细胞粘附和/或白细胞迁移程度引起的疾病或与之相关的疾病，并且为了预防，缓解或治愈粘连 和/或白细胞迁移应减少。

    Use of phenylmethimazoles, methimazole derivatives, and tautomeric cyclic thiones for the treatment of autoimmune/inflammatory diseases associated with toll-like receptor overexpression
    2.
    发明申请
    Use of phenylmethimazoles, methimazole derivatives, and tautomeric cyclic thiones for the treatment of autoimmune/inflammatory diseases associated with toll-like receptor overexpression 审中-公开
    苯甲嘧啶，甲巯咪唑衍生物和互变异构环状硫堇用于治疗与同样受体过表达相关的自身免疫/炎性疾病

    公开(公告)号：US20060211752A1

    公开(公告)日：2006-09-21

    申请号：US11130922

    申请日：2005-05-17

    申请人： Leonard Kohn ,  Norikazu Harii ,  Uruguaysito Benavides-Peralta ,  Mariana Gonzalez-Murguiondo ,  Christopher Lewis ,  Giorgio Napolitano ,  Cesidio Giuliani ,  Ramiro Malgor ,  Douglas Goetz

    发明人： Leonard Kohn ,  Norikazu Harii ,  Uruguaysito Benavides-Peralta ,  Mariana Gonzalez-Murguiondo ,  Christopher Lewis ,  Giorgio Napolitano ,  Cesidio Giuliani ,  Ramiro Malgor ,  Douglas Goetz

    IPC分类号： A61K31/4166

    CPC分类号： A61K31/4164 ,  A61K31/4166 ,  A61K31/56 ,  A61K45/06 ,  Y02A50/411

    摘要： The present invention relates to the treatment of autoimmune and/or inflammatory diseases associated with overexpression of Toll-like receptor 3 (TLR3) as well as Toll-like receptor 4 (TLR4) and/or TLR3/TLR4 signaling in nonimmune cells, monocytes, macrophages, and/or dendritic cells in association with related pathologies. This invention also relates to the use of phenylmethimazoles, methimazole derivatives, and tautomeric cyclic thiones for the treatment of autoimmune and inflammatory diseases associated with Toll-like receptor 3 (TLR3) as well as Toll-like receptor 4 (TLR4) and/or TLR3/TLR4 signaling in nonimmune cells, monocytes, macrophages, and/or dendritic cells in association with related pathologies. This invention also relates to treating a subject having a disease or condition associated with abnormal Toll-like receptor 3 as well as Toll-like receptor 4 and/or TLR3/TLR4 signaling in nonimmune cells, monocytes, macrophages, and/or dendritic cells in association with related pathologies. The present invention also relates to the treatment of autoimmune-inflammatory pathologies and chemokine and cytokine-mediated diseases associated with TLR overexpression and signaling. This invention also relates to pharmaceutical formulations capable of inhibiting the IRF-3/Type 1 IFN/STAT/ISRE/IRF-1 pathway associated with Toll-like receptor overexpression or signaling.

    摘要翻译： 本发明涉及治疗与非免疫细胞，单核细胞中Toll样受体3（TLR3）和Toll样受体4（TLR4）和/或TLR3 / TLR4信号传导过度相关的自身免疫性和/或炎性疾病， 巨噬细胞和/或与相关病理学相关的树突状细胞。 本发明还涉及苯甲基咪唑，甲巯咪唑衍生物和互变异构环状硫堇用于治疗与Toll样受体3（TLR3）以及Toll样受体4（TLR4）和/或TLR3相关的自身免疫性和炎性疾病的用途 / TLR4信号传导在非免疫细胞，单核细胞，巨噬细胞和/或树突状细胞中，与相关病理学相关。 本发明还涉及在非免疫细胞，单核细胞，巨噬细胞和/或树突细胞中治疗具有与异常Toll样受体3以及Toll样受体4和/或TLR3 / TLR4信号传导相关的疾病或病症的受试者 与相关病理学关联。 本发明还涉及治疗与TLR过表达和信号传导相关的自身免疫性炎症病理和趋化因子和细胞因子介导的疾病。 本发明还涉及能够抑制与Toll样受体过表达或信号传导相关的IRF-3/1型IFN / STAT / ISRE / IRF-1途径的药物制剂。