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1. 发明申请

US20090258901A1 LIGANDS FOR MONOAMINE RECEPTORS AND TRANSPORTERS, AND METHODS OF USE THEREOF 有权
标题翻译：单体受体和运输商的配体及其使用方法
公开(公告)号：US20090258901A1
公开(公告)日：2009-10-15
申请号：US12403311
申请日：2009-03-12
申请人： Brian M. Aquila , Thomas D. Bannister , Gregory D. Cuny , James R. Hauske , Joanne M. Holland , Paul E. Persons , Heike Radeke , Fengjiang Wang , Liming Ahao
发明人： Brian M. Aquila , Thomas D. Bannister , Gregory D. Cuny , James R. Hauske , Joanne M. Holland , Paul E. Persons , Heike Radeke , Fengjiang Wang , Liming Ahao
IPC分类号： A61K31/445 , C07D211/22 , C07D211/20 , A61P35/00
CPC分类号： C40B40/04 , C07B2200/11 , C07C255/46 , C07C2601/04 , C07D205/02 , C07D207/06 , C07D207/08 , C07D207/09 , C07D211/12 , C07D211/16 , C07D211/18 , C07D211/20 , C07D211/26 , C07D211/32 , C07D211/40 , C07D211/42 , C07D211/60 , C07D233/04 , C07D233/10 , C07D265/30 , C07D267/10 , C07D303/08 , C07D401/06 , C07D401/12 , C07D405/06 , C07D405/12 , C07D413/06 , C40B30/04 , C40B50/14
摘要： One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including dopamine, serotonin, or norepinephrine transporters. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, schizophrenia, Parkinson's disease, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, and Tourette's syndrome. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds, and the screening of those libraries for biological activity, e.g., in assays based on dopamine transporters.
摘要翻译：本发明的一个方面涉及杂环化合物。本发明的第二方面涉及杂环化合物作为各种哺乳动物细胞受体（包括多巴胺，5-羟色胺或去甲肾上腺素转运蛋白）的配体的用途。本发明的化合物可用于治疗多种疾病，疾病，其包括但不限于成瘾，焦虑，抑郁，性功能障碍，高血压，偏头痛，阿尔茨海默病，肥胖，呕吐，精神病，精神分裂症，帕金森病，炎症性疼痛，神经性疼痛，Lesche-Nyhane病，Wilson氏病和Tourette综合征。本发明的另一方面涉及杂环化合物的组合文库的合成，以及用于生物活性的那些文库的筛选，例如在基于多巴胺转运蛋白的测定中。

2. 发明授权

US07816375B2 Ligands for monoamine receptors and transporters, and methods of use thereof 有权
标题翻译：单胺受体和转运蛋白的配体及其使用方法
公开(公告)号：US07816375B2
公开(公告)日：2010-10-19
申请号：US12403311
申请日：2009-03-12
申请人： Brian M. Aquila , Thomas D. Bannister , Gregory D. Cuny , James R. Hauske , Joanne M. Holland , Paul E. Persons , Heike Radeke , Fengjiang Wang , Liming Shao
发明人： Brian M. Aquila , Thomas D. Bannister , Gregory D. Cuny , James R. Hauske , Joanne M. Holland , Paul E. Persons , Heike Radeke , Fengjiang Wang , Liming Shao
IPC分类号： A61P25/00 , A61K31/445 , C07D211/00
CPC分类号： C40B40/04 , C07B2200/11 , C07C255/46 , C07C2601/04 , C07D205/02 , C07D207/06 , C07D207/08 , C07D207/09 , C07D211/12 , C07D211/16 , C07D211/18 , C07D211/20 , C07D211/26 , C07D211/32 , C07D211/40 , C07D211/42 , C07D211/60 , C07D233/04 , C07D233/10 , C07D265/30 , C07D267/10 , C07D303/08 , C07D401/06 , C07D401/12 , C07D405/06 , C07D405/12 , C07D413/06 , C40B30/04 , C40B50/14
摘要： One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including dopamine, serotonin, or norepinephrine transporters. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, schizophrenia, Parkinson's disease, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, and Tourette's syndrome. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds, and the screening of those libraries for biological activity, e.g., in assays based on dopamine transporters.
摘要翻译：本发明的一个方面涉及杂环化合物。本发明的第二方面涉及杂环化合物作为各种哺乳动物细胞受体（包括多巴胺，5-羟色胺或去甲肾上腺素转运蛋白）的配体的用途。本发明的化合物可用于治疗多种疾病，疾病，其包括但不限于成瘾，焦虑，抑郁，性功能障碍，高血压，偏头痛，阿尔茨海默病，肥胖，呕吐，精神病，精神分裂症，帕金森病，炎症性疼痛，神经性疼痛，Lesche-Nyhane病，Wilson氏病和Tourette综合征。本发明的另一方面涉及杂环化合物的组合文库的合成，以及用于生物活性的那些文库的筛选，例如在基于多巴胺转运蛋白的测定中。

3. 发明授权

US07517892B2 Ligands for monoamine receptors and transporters, and methods of use thereof 有权
标题翻译：单胺受体和转运蛋白的配体及其使用方法
公开(公告)号：US07517892B2
公开(公告)日：2009-04-14
申请号：US09951130
申请日：2001-09-12
申请人： Brian M. Aquila , Thomas D. Bannister , Gregory D. Cuny , James R. Hauske , Joanne M. Holland , Paul E. Persons , Heike Radeke , Fengjiang Wang , Liming Shao
发明人： Brian M. Aquila , Thomas D. Bannister , Gregory D. Cuny , James R. Hauske , Joanne M. Holland , Paul E. Persons , Heike Radeke , Fengjiang Wang , Liming Shao
IPC分类号： A61P25/00 , A61K31/445 , C07D211/00 , C07D401/00
CPC分类号： C40B40/04 , C07B2200/11 , C07C255/46 , C07C2601/04 , C07D205/02 , C07D207/06 , C07D207/08 , C07D207/09 , C07D211/12 , C07D211/16 , C07D211/18 , C07D211/20 , C07D211/26 , C07D211/32 , C07D211/40 , C07D211/42 , C07D211/60 , C07D233/04 , C07D233/10 , C07D265/30 , C07D267/10 , C07D303/08 , C07D401/06 , C07D401/12 , C07D405/06 , C07D405/12 , C07D413/06 , C40B30/04 , C40B50/14
摘要： One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including dopamine, serotonin, or norepinephrine transporters. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, schizophrenia, Parkinson's disease, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, and Tourette's syndrome. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds, and the screening of those libraries for biological activity, e.g., in assays based on dopamine transporters.
摘要翻译：本发明的一个方面涉及杂环化合物。本发明的第二方面涉及杂环化合物作为各种哺乳动物细胞受体（包括多巴胺，5-羟色胺或去甲肾上腺素转运蛋白）的配体的用途。本发明的化合物可用于治疗多种疾病，疾病，其包括但不限于成瘾，焦虑，抑郁，性功能障碍，高血压，偏头痛，阿尔茨海默病，肥胖，呕吐，精神病，精神分裂症，帕金森病，炎症性疼痛，神经性疼痛，Lesche-Nyhane病，Wilson氏病和Tourette综合征。本发明的另一方面涉及杂环化合物的组合文库的合成，以及用于生物活性的那些文库的筛选，例如在基于多巴胺转运蛋白的测定中。

4. 发明授权

US07294637B2 Method of treating addiction or dependence using a ligand for a monamine receptor or transporter 有权
标题翻译：用单胺受体或转运蛋白配体治疗成瘾或依赖的方法
公开(公告)号：US07294637B2
公开(公告)日：2007-11-13
申请号：US10771519
申请日：2004-02-04
申请人： Brian M. Aquila , Thomas D. Bannister , Gregory D. Cuny , James R. Hauske , Joanne M. Holland , Paul E. Persons , Heike S. Radeke , Fengjiang Wang , Liming Shao
发明人： Brian M. Aquila , Thomas D. Bannister , Gregory D. Cuny , James R. Hauske , Joanne M. Holland , Paul E. Persons , Heike S. Radeke , Fengjiang Wang , Liming Shao
IPC分类号： A61P25/30 , A61K31/445 , C07D211/00 , C07D401/00
CPC分类号： A61K31/397 , A61K31/40 , A61K31/445 , A61K31/55 , C07B2200/11 , C07C255/46 , C07C2601/04 , C07D205/02 , C07D207/06 , C07D207/08 , C07D207/09 , C07D211/12 , C07D211/16 , C07D211/18 , C07D211/20 , C07D211/26 , C07D211/32 , C07D211/40 , C07D211/42 , C07D211/60 , C07D233/04 , C07D233/10 , C07D265/30 , C07D267/10 , C07D303/08 , C07D401/06 , C07D401/12 , C07D405/06 , C07D405/12 , C07D413/06 , C40B40/04
摘要： One aspect of the present invention relates to a method of treating of drug addiction or drug dependence in a mammal, comprising the step of administering to a mammal in need thereof a therapuetically effective amount of a heterocyclic compound, e.g., a 3-substituted piperidine. In a preferred embodiment, the method of the present invention treats cocaine addiction or methamphetamine addiction.
摘要翻译：本发明的一个方面涉及一种治疗哺乳动物药物成瘾或药物依赖的方法，其包括向有需要的哺乳动物施用治疗有效量的杂环化合物，例如3-取代哌啶的步骤。在优选的实施方案中，本发明的方法治疗可卡因成瘾或甲基苯丙胺成瘾。

5. 发明授权

US07132551B2 Ligands for monoamine receptors and transporters, and methods of use thereof 有权
公开(公告)号：US07132551B2
公开(公告)日：2006-11-07
申请号：US10607457
申请日：2003-06-26
申请人： Brian M. Aquila , Thomas D. Bannister , Gregory D. Cuny , James R. Hauske , Joanne M. Holland , Paul E. Persons , Heike S. Radeke , Fengjiang Wang , Liming Shao
发明人： Brian M. Aquila , Thomas D. Bannister , Gregory D. Cuny , James R. Hauske , Joanne M. Holland , Paul E. Persons , Heike S. Radeke , Fengjiang Wang , Liming Shao
IPC分类号： C07D207/00
CPC分类号： C40B40/04 , C07B2200/11 , C07C255/46 , C07C2601/04 , C07D205/02 , C07D207/06 , C07D207/08 , C07D207/09 , C07D211/12 , C07D211/16 , C07D211/18 , C07D211/20 , C07D211/26 , C07D211/32 , C07D211/40 , C07D211/42 , C07D211/60 , C07D233/04 , C07D233/10 , C07D265/30 , C07D267/10 , C07D303/08 , C07D401/06 , C07D401/12 , C07D405/06 , C07D405/12 , C07D413/06 , C40B30/04 , C40B50/14
摘要： One aspect of the present invention relates to heterocyclic compounds. A second aspect of the present invention relates to the use of the heterocyclic compounds as ligands for various mammalian cellular receptors, including dopamine, serotonin, or norepinephrine transporters. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, schizophrenia, Parkinson's disease, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, and Tourette's syndrome. An additional aspect of the present invention relates to the synthesis of combinatorial libraries of the heterocyclic compounds, and the screening of those libraries for biological activity, e.g., in assays based on dopamine transporters.

6. 发明授权

US06699866B2 Thiazole and other heterocyclic ligands for mammalian dopamine, muscarinic and serotonin receptors and transporters, and methods of use thereof 有权
标题翻译：噻唑和其他哺乳动物多巴胺，毒蕈碱和5-羟色胺受体和转运蛋白的杂环配体及其使用方法
公开(公告)号：US06699866B2
公开(公告)日：2004-03-02
申请号：US10123089
申请日：2002-04-12
申请人： Gregory D. Cuny , James R. Hauske , Michele L. R. Heffernan , Joanne M. Holland , Paul E. Persons , Heike Radeke
发明人： Gregory D. Cuny , James R. Hauske , Michele L. R. Heffernan , Joanne M. Holland , Paul E. Persons , Heike Radeke
IPC分类号： A61K31535
CPC分类号： C07D271/07 , C07D277/42 , C07D413/12 , C07D417/04 , C07D417/06 , C07D417/12 , C07D417/14
摘要： One aspect of the present invention relates to novel heterocyclic compounds. A second aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for various mammalian cellular receptors, including G-protein coupled receptors. A third aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for mammalian dopamine, muscarinic or serotonin receptors or transporters. Another aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for mammalian dopamine, muscarinic or serotonin receptors. The compounds of the present invention will also find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, analgesia, schizophrenia, Parkinson's disease, restless leg syndrome, sleeping disorders, attention deficit hyperactivity disorder, irritable bowel syndrome, premature ejaculation, menstrual dysphoria syndrome, urinary incontinence, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, Tourette's syndrome, psychiatric disorders, stroke, senile dementia, peptic ulcers, pulmonary obstruction disorders, and asthma.
摘要翻译：本发明的一个方面涉及新的杂环化合物。本发明的第二方面涉及新型杂环化合物作为各种哺乳动物细胞受体（包括G蛋白偶联受体）的配体的用途。本发明的第三方面涉及新型杂环化合物作为哺乳动物多巴胺，毒蕈碱或血清素受体或转运蛋白的配体的用途。本发明的另一方面涉及新型杂环化合物作为哺乳动物多巴胺，毒蕈碱或血清素受体的配体的用途。本发明的化合物还可用于治疗影响哺乳动物的许多疾病，病症和疾病，包括但不限于成瘾，焦虑，抑郁，性功能障碍，高血压，偏头痛，阿尔茨海默病，肥胖，呕吐，精神病，镇痛，精神分裂症，帕金森病，不宁腿综合征，睡眠障碍，注意力缺陷多动障碍，肠易激综合征，早泄，月经性烦躁综合征，尿失禁，炎性疼痛，神经性疼痛，Lesche-Nyhane疾病，Wilson氏病，Tourette综合征，精神障碍，中风，老年痴呆，消化性溃疡，肺梗阻障碍和哮喘。

7. 发明授权

US07087623B2 Thiazole and other heterocyclic ligands for mammalian dopamine, muscarinic and serotonin receptors and transporters, and methods of use thereof 有权
公开(公告)号：US07087623B2
公开(公告)日：2006-08-08
申请号：US10786612
申请日：2004-02-25
申请人： Gregory D. Cuny , James R. Hauske , Michele L. R. Heffernan , Joanne M. Holland , Paul E. Persons , Heike Radeke
发明人： Gregory D. Cuny , James R. Hauske , Michele L. R. Heffernan , Joanne M. Holland , Paul E. Persons , Heike Radeke
IPC分类号： A61K31/445 , C07D401/00
CPC分类号： C07D271/07 , C07D277/42 , C07D413/12 , C07D417/04 , C07D417/06 , C07D417/12 , C07D417/14
摘要： One aspect of the present invention relates to novel heterocyclic compounds. A second aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for various mammalian cellular receptors, including G-protein coupled receptors. A third aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for mammalian dopamine, muscarinic or serotonin receptors or transporters. Another aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for mammalian dopamine, muscarinic or serotonin receptors. The compounds of the present invention will also find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, analgesia, schizophrenia, Parkinson's disease, restless leg syndrome, sleeping disorders, attention deficit hyperactivity disorder, irritable bowel syndrome, premature ejaculation, menstrual dysphoria syndrome, urinary incontinence, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, Tourette's syndrome, psychiatric disorders, stroke, senile dementia, peptic ulcers, pulmonary obstruction disorders, and asthma.

8. 发明授权

US07446115B2 Peptidomimetic ligands for cellular receptors and ion channels 有权
标题翻译：肽模拟配体的细胞受体和离子通道
公开(公告)号：US07446115B2
公开(公告)日：2008-11-04
申请号：US11512056
申请日：2006-08-29
申请人： Paul E. Persons , Joanne M. Holland , James R. Hauske
发明人： Paul E. Persons , Joanne M. Holland , James R. Hauske
IPC分类号： A61K31/40 , A61K31/4025 , A61K31/472 , C07D207/14 , C07D211/56 , C07D217/12 , C07D223/16
CPC分类号： C07D295/185 , C07B2200/07 , C07C275/26 , C07C275/28 , C07C275/30 , C07C275/34 , C07D207/14 , C07D207/16 , C07D213/56 , C07D217/26 , C07D401/12
摘要： One aspect of the present invention relates to novel peptidomometic compounds. A second aspect of the present invention relates to the use of the novel peptidomimetic compounds as ligands—agonists or antagonists—for various cellular receptors, e.g., G-protein-coupled receptors and opioid receptors, and various cellular ion channels, e.g., sodium and calcium. In certain embodiments, compounds of the present invention preferentially or selectively inhibit sodium or calcium ion channels. In certain embodiments, compounds of the present invention preferentially or selectively agonize or antagonize μ opioid receptors. In certain embodiments, compounds of the present invention preferentially or selectively inhibit sodium or calcium ion channels and agonize or antagonize μ-opioid receptors.
摘要翻译：本发明的一个方面涉及新颖的肽模拟化合物。本发明的第二方面涉及新型拟肽化合物作为配体 - 激动剂或拮抗剂 - 用于各种细胞受体，例如G-蛋白偶联受体和阿片受体，以及各种细胞离子通道（例如钠和钙。在某些实施方案中，本发明的化合物优选或选择性地抑制钠离子或钙离子通道。在某些实施方案中，本发明的化合物优选地或选择性地激动或拮抗μ阿片受体。在某些实施方案中，本发明的化合物优选地或选择性地抑制钠离子通道或钙离子通道并且激动或拮抗μ-阿片受体。

9. 发明授权

US07115664B2 Peptidomimetic ligands for cellular receptors and ion channels 有权
标题翻译：肽模拟配体的细胞受体和离子通道
公开(公告)号：US07115664B2
公开(公告)日：2006-10-03
申请号：US10203279
申请日：2001-02-27
申请人： Paul E. Persons , Joanne M. Holland , James Hauske
发明人： Paul E. Persons , Joanne M. Holland , James Hauske
IPC分类号： A61K31/17 , C07C275/26 , C07C275/28 , C07D3351/18
CPC分类号： C07D295/185 , C07B2200/07 , C07C275/26 , C07C275/28 , C07C275/30 , C07C275/34 , C07D207/14 , C07D207/16 , C07D213/56 , C07D217/26 , C07D401/12
摘要： One aspect of the present invention relates to novel peptidomimetic compounds. A second aspect of the present invention relates to the use of the novel peptidomimetic compounds as ligands—agonists or antagonists—for various cellular receptors, e.g., G-protein-coupled receptors and opioid receptors, and various cellular ion channels, e.g., sodium and calcium. In certain embodiments, compounds of the present invention preferentially or selectively inhibit sodium or calcium ion channels. In certain embodiments, compounds of the present invention preferentially or selectively agonize or antagonize $gm opioid receptors. In certain embodiments, compounds of the present invention preferentially or selectively inhibit sodium or calcium ion channels and agonize or antagonize $gm-opioid receptors
摘要翻译：本发明的一个方面涉及新的拟肽化合物。本发明的第二方面涉及新型拟肽化合物作为配体 - 激动剂或拮抗剂 - 用于各种细胞受体（例如G-蛋白偶联受体和阿片受体）和各种细胞离子通道（例如钠和钙。在某些实施方案中，本发明的化合物优选或选择性地抑制钠离子或钙离子通道。在某些实施方案中，本发明的化合物优选地或选择性地激动或拮抗$ g阿片受体。在某些实施方案中，本发明的化合物优先或选择性地抑制钠离子通道或钙离子通道，并激动或拮抗$ gm-阿片受体

10. 发明授权

US07030122B2 1,4-disubstituted piperazine ligands for neurotransmitter receptors 有权
标题翻译：用于神经递质受体的1,4-二取代哌嗪配体
公开(公告)号：US07030122B2
公开(公告)日：2006-04-18
申请号：US10401106
申请日：2003-03-27
申请人： James R. Hauske , Joanne M. Holland , Heike S. Radeke
发明人： James R. Hauske , Joanne M. Holland , Heike S. Radeke
IPC分类号： A61K31/497 , A61K31/4965 , C07D401/12 , C07D241/04
CPC分类号： C07D221/04 , A61K31/495 , C07D221/16 , C07D295/13 , C07D487/04
摘要： One aspect of the present invention relates to novel heterocyclic compounds. A second aspect of the present invention relates to the use of the novel heterocyclic compounds as ligands for various cellular receptors, including serotonin receptors and dopamine receptors. The compounds of the present invention will find use in the treatment of numerous ailments, conditions and diseases which afflict mammals, including but not limited to addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, analgesia, schizophrenia, Parkinson's disease, restless leg syndrome, sleeping disorders, attention deficit hyperactivity disorder, irritable bowel syndrome, premature ejaculation, menstrual dysphoria syndrome, urinary incontinence, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, Tourette's syndrome, psychiatric disorders, stroke, and senile dementia.
摘要翻译：本发明的一个方面涉及新的杂环化合物。本发明的第二方面涉及新型杂环化合物作为各种细胞受体（包括血清素受体和多巴胺受体）的配体的用途。本发明的化合物可用于治疗多种疾病，疾病，其包括但不限于成瘾，焦虑，抑郁，性功能障碍，高血压，偏头痛，阿尔茨海默病，肥胖，呕吐，精神病，止痛，精神分裂症，帕金森病，不宁腿综合征，睡眠障碍，注意缺陷多动障碍，肠易激综合征，早泄，月经性烦躁综合症，尿失禁，炎性疼痛，神经性疼痛，莱氏阴道炎，威尔逊病，图雷特综合征，精神障碍，中风和老年痴呆。

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