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。

公开(公告)号：US20060058365A1

公开(公告)日：2006-03-16

申请号：US10912948

申请日：2004-08-06

申请人： Leonard Kohn ,  Douglas Goetz ,  Uruguaysito Benavides-Peralta ,  Mariana Gonzalez-Murguiondo ,  Norikazu Harii ,  Christopher Lewis ,  Giorgio Napolitano ,  Nilesh Dagia

发明人： Leonard Kohn ,  Douglas Goetz ,  Uruguaysito Benavides-Peralta ,  Mariana Gonzalez-Murguiondo ,  Norikazu Harii ,  Christopher Lewis ,  Giorgio Napolitano ,  Nilesh Dagia

IPC分类号： A61K31/4166

CPC分类号： A61K31/4164 ,  Y02A50/402 ,  Y02A50/411

摘要： The present invention relates to the treatment of inflammatory bowel disease (IBD) and related gastrointestinal pathologies. This invention also relates to the treatment of cytokine-mediated diseases, including tumor necrosis factor-α (TNFα)-induced diseases and/or chemokine-mediated diseases. This invention also relates to treating an animal having a disease or condition associated with Toll-like receptor 4. Specifically, the present invention relates to the treatment of inflammatory bowel disease (IBD) and related gastrointestinal pathologies that are cytokine-mediated or associated with Toll-like receptor 4. More specifically, this invention is directed to methods for treating or preventing IBD and related gastrointestinal pathologies using methimazole derivatives and tautomeric cyclic thiones. This invention is also directed to pharmaceutical compositions containing methimazole derivatives and tautomeric cyclic thiones, which are useful for the treatment or prophylaxis of IBD and related gastrointestinal pathologies. This invention also relates to pharmaceutical formulations capable of inhibiting tumor necrosis factor-α (TNFα)-induced vascular cell adhesion molecule-1 (VCAM-1) expression and the resulting leukocyte-endothelial cell adhesion for the inhibition and prevention of inflammatory bowel syndrome and related gastrointestinal pathologies.

摘要翻译： 本发明涉及炎症性肠病（IBD）和相关胃肠道病理学的治疗。 本发明还涉及细胞因子介导的疾病的治疗，包括肿瘤坏死因子-α（TNFα）诱导的疾病和/或趋化因子介导的疾病。 本发明还涉及治疗具有与Toll样受体4相关的疾病或病症的动物。具体而言，本发明涉及炎症性肠病（IBD）的治疗以及细胞因子介导或与Toll相关的相关胃肠病理 类似受体4.更具体地，本发明涉及使用甲巯咪唑衍生物和互变异构环状硫堇治疗或预防IBD和相关胃肠道病理学的方法。 本发明还涉及含有甲巯咪唑衍生物和互变异构环状硫堇的药物组合物，其可用于治疗或预防IBD和相关的胃肠道病理。 本发明还涉及能够抑制肿瘤坏死因子-α（TNFα）诱导的血管细胞粘附分子-1（VCAM-1）表达的药物制剂以及由此产生的白细胞内皮细胞粘附以抑制和预防炎症性肠综合征和 相关的胃肠道病变。

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。

公开(公告)号：US20050186264A1

公开(公告)日：2005-08-25

申请号：US10993825

申请日：2004-11-19

申请人： Mohammad Kiani ,  Douglas Goetz

发明人： Mohammad Kiani ,  Douglas Goetz

IPC分类号： A61K9/51 ,  A61K47/48 ,  C07K16/18 ,  C07K16/28 ,  A61K39/395 ,  A61K9/127

CPC分类号： A61K9/5153 ,  A61K47/6843 ,  A61K47/6849 ,  A61K2039/505 ,  C07K16/18 ,  C07K16/2821

摘要： The present invention provides targeted delivery systems to deliver pharmaceuticals to irradiated tissue comprising a biomolecule carrier, a targeting moiety to cellular adhesion molecules and a pharmaceutical. The present invention also provides methods of selectively targeting endothelial tissue for delivery of a pharmaceutical thereto and of treating a pathophysiological state in an individual using the targeted delivery systems disclosed herein. Further provided is a method of optimizing an immunoliposome for specific targeting of a pharmaceutical encapsulated therein to irradiated tissue by selecting a liposome that has a greater rate of adhesion to the irradiated tissue than a rate of uptake by the reticuloendothelial system.

摘要翻译： 本发明提供了靶向递送系统，以将药物递送到包含生物分子载体，靶向部分到细胞粘附分子和药物的辐照组织。 本发明还提供了选择性靶向内皮组织以递送其药物并使用本文公开的靶向递送系统治疗个体的病理生理状态的方法。 还提供了一种优化免疫脂质体的方法，用于通过选择与被照射的组织具有更大的粘附速率的脂质体比通过网状内皮系统摄取的速率，将包封在其中的药物的特异靶向特异性靶向给照射的组织。