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1. 发明授权

US06683061B1 Enzyme catalyzed therapeutic activation 失效
标题翻译：酶催化治疗激活
公开(公告)号：US06683061B1
公开(公告)日：2004-01-27
申请号：US09856127
申请日：2001-10-10
申请人： H. Michael Shepard , Ming Fai Chan , Michael P. Groziak
发明人： H. Michael Shepard , Ming Fai Chan , Michael P. Groziak
IPC分类号： A01N4304
CPC分类号： C07H19/06
摘要： This invention provides novel substrate compounds that selectively inhibit the proliferation of pathological cells, for example, pathological calls that endogenously overexpress a target enzyme that confers resistance to biologic and chemotherapeutic agents. The enzyme acts on a substrate compound to 1) convert it to a cellular toxin and/or 2) release a toxic byproduct. In one embodiment, the activity of the target enzyme has been greatly enhanced in a target cell as a result of loss of tumor suppressor function and/or selection resulting from previous exposure to chemotherapy. In another embodiment, the pathological cell contains a target enzyme that is an expression product of an infectious agent in the cell. Further provided by this invention is a method for treating a subject by delivering to the subject a prodrug as described herein. The prodrugs of this invention may be used alone or in combination with other chemotherapeutics or alternative anti-cancer therapies such as radiation.
摘要翻译：本发明提供了选择性抑制病理细胞增殖的新型底物化合物，例如内源性过度表达赋予生物和化学治疗剂抗性的靶酶的病理学调节。该酶作用于底物化合物以1）将其转化为细胞毒素和/或2）释放有毒副产物。在一个实施方案中，由于先前暴露于化学疗法导致的肿瘤抑制功能和/或选择的丧失，靶细胞的活性已大大增强。在另一个实施方案中，病理细胞含有作为细胞中感染因子的表达产物的靶酶。本发明进一步提供的是通过向受试者递送本文所述的前药来治疗受试者的方法。本发明的前药可以单独使用或与其它化学治疗剂或替代的抗癌疗法如辐射一起使用。

2. 发明授权

US6083936A Boron heterocycle steroid mimics and associated pharmaceutical compositions and methods of use 失效
标题翻译：硼杂环类固醇模拟物和相关药物组合物和使用方法
公开(公告)号：US6083936A
公开(公告)日：2000-07-04
申请号：US236948
申请日：1999-01-25
申请人： Michael P. Groziak
发明人： Michael P. Groziak
IPC分类号： A61K51/00 , A61K31/69 , A61K49/00 , A61P5/30 , A61P11/00 , A61P15/00 , A61P19/10 , A61P35/00 , C07F5/02 , A01N55/58 , C07C69/96 , C07F5/04
CPC分类号： C07F5/025 , C07F5/02
摘要： Boron heterocycle steroid mimics are provided that are useful as pharmaceutical agents, particularly in the treatment of estrogen-dependent disorders such as estrogen-dependent cancers. The compounds are also useful in diagnostic techniques such as magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), in boron neutron capture therapy, and in fluorescence emission-based modalities. Pharmaceutical formulations and methods of using the novel compounds are provided as well.
摘要翻译：提供硼杂环类固醇模拟物，其可用作药剂，特别是用于治疗雌激素依赖性疾病如雌激素依赖性癌症。该化合物也可用于诊断技术，例如磁共振成像（MRI）和磁共振光谱（MRS），硼中子捕获治疗和基于荧光发射的模式。还提供了药物制剂和使用新化合物的方法。

3. 发明授权

US07601703B2 Enzyme catalyzed therapeutic agents 有权
公开(公告)号：US07601703B2
公开(公告)日：2009-10-13
申请号：US09782721
申请日：2001-02-12
申请人： H. Michael Shepard , Michael P. Groziak
发明人： H. Michael Shepard , Michael P. Groziak
IPC分类号： A61K31/70 , C07H19/10
CPC分类号： C07H19/20 , A61K47/54 , A61K47/555 , A61K47/556 , A61K47/67 , B82Y5/00 , C07F9/6512 , C07H19/06 , C07H19/10
摘要： This invention provides a method for identifying potential therapeutic agents by contacting a target cell with a candidate therapeutic agent which is a selective substrate for an endogenous, intracellular enzyme in the cell which is enhanced in its expression as a result of selection by biologic or chemotherapy. This invention also provides methods and examples of molecules for selectively killing a pathological cell by contacting the cell with a prodrug that is a selective substrate for an endogenous, intracellular enzyme. The prodrug is subsequently converted to a cellular toxin. Further provided by this invention is a method for treating a pathology characterized by pathological, hyperproliferative cells in a subject by administering to the subject a prodrug that is a selective substrate for an endogenous, overexpressed, intracellular enzyme, and converted by the enzyme to a cellular toxin in the hyperproliferative cell.

4. 发明授权

US06339151B1 Enzyme catalyzed therapeutic agents 有权
标题翻译：酶催化治疗剂
公开(公告)号：US06339151B1
公开(公告)日：2002-01-15
申请号：US09235961
申请日：1999-01-22
申请人： H. Michael Shepard , Michael P. Groziak
发明人： H. Michael Shepard , Michael P. Groziak
IPC分类号： C07H19073
CPC分类号： C07H19/20 , A61K47/54 , A61K47/555 , A61K47/556 , A61K47/67 , B82Y5/00 , C07F9/6512 , C07H19/06 , C07H19/10
摘要： This invention provides a method for identifying potential therapeutic agents by contacting a target cell with a candidate therapeutic agent which is a selective substrate for an endogenous, intracellular enzyme in the cell which is enhanced in its expression as a result of selection by biologic or chemotherapy. This invention also provides methods and examples of molecules for selectively killing a pathological cell by contacting the cell with a prodrug that is a selective substrate for an endogenous, intracellular enzyme. The prodrug is subsequently converted to a cellular toxin. Further provided by this invention is a method for treating a pathology characterized by pathological, hyperproliferative cells in a subject by administering to the subject a prodrug that is a selective substrate for an endogenous, overexpressed, intracellular enzyme, and converted by the enzyme to a cellular toxin in the hyperproliferative cell.
摘要翻译：本发明提供了一种通过使靶细胞与候选治疗剂接触来鉴定潜在治疗剂的方法，所述候选治疗剂是细胞中的内源性细胞内酶的选择性底物，其作为通过生物或化疗选择的结果而增强其表达。本发明还提供了通过使细胞与作为内源性细胞内酶的选择性底物的前药接触来选择性杀死病理细胞的分子的方法和实施例。随后将前药转化为细胞毒素。本发明进一步提供的是通过向受试者施用作为内源性，过表达的细胞内酶的选择性底物并由酶转化成细胞的前体药物来治疗受试者中病理学，过度增殖细胞特征的病理学的方法毒素在过度增殖细胞中。

5. 发明授权

US07605144B2 Enzyme catalyzed therapeutic compounds 失效
标题翻译：酶催化治疗化合物
公开(公告)号：US07605144B2
公开(公告)日：2009-10-20
申请号：US10681418
申请日：2003-10-07
申请人： H. Michael Shepard , Ming Fai Chan , Michael P. Groziak
发明人： H. Michael Shepard , Ming Fai Chan , Michael P. Groziak
IPC分类号： A61K31/70 , C07H19/10 , C12Q1/66 , C12P29/00 , C12P31/00
CPC分类号： C07H19/06
摘要： This invention provides novel compounds selected from the group consisting of a 1,5-substituted pyrimidine derivative or analog and substituted furano-pyrimidone analogs. The compounds are useful to treat or prevent diseases such as cancer.
摘要翻译：本发明提供了选自1,5-取代的嘧啶衍生物或类似物和取代的呋喃 - 嘧啶酮类似物的新化合物。该化合物可用于治疗或预防诸如癌症的疾病。

6. 发明授权

US06248305B1 Boron heterocycle steroid mimics and associated pharmaceutical compositions and methods of use 失效
标题翻译：硼杂环类固醇模拟物和相关药物组合物和使用方法
公开(公告)号：US06248305B1
公开(公告)日：2001-06-19
申请号：US09490601
申请日：2000-01-25
申请人： Michael P. Groziak
发明人： Michael P. Groziak
IPC分类号： A61K5100
CPC分类号： C07F5/025 , C07F5/02
摘要： Boron heterocycle steroid mimics are provided that are useful as pharmaceutical agents, particularly in the treatment of estrogen-dependent disorders such as estrogen-dependent cancers. The compounds are also useful in diagnostic techniques such as magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), in boron neutron capture therapy, and in fluorescence emission-based modalities. Pharmaceutical formulations and methods of using the novel compounds are provided as well.
摘要翻译：提供硼杂环类固醇模拟物，其可用作药剂，特别是用于治疗雌激素依赖性疾病如雌激素依赖性癌症。该化合物也可用于诊断技术，例如磁共振成像（MRI）和磁共振光谱（MRS），硼中子捕获治疗和基于荧光发射的模式。还提供了药物制剂和使用新化合物的方法。

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