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41. 发明申请

WO2004060283A3 NITROSATED AND NITROSYLATED RAPAMYCIN COMPOUNDS, COMPOSITIONS AND METHODS OF USE 审中-公开
公开(公告)号：WO2004060283A3
公开(公告)日：2004-07-22
申请号：PCT/US2003/039562
申请日：2003-12-15
申请人： NITROMED, INC. , GARVEY, David, S.
发明人： GARVEY, David, S.
IPC分类号： C07D498/18
摘要： The invention describes novel nitrosated and/or nitrosylated rapamycin compounds, and novel compositions comprising at least one nitrosated and/or nitrosylated rapamycin compound, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one rapamycin compound and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The compounds and compositions of the invention can also be bound to a matrix. The invention also provides methods for treating and/or preventing cardiovascular diseases, for the prevention of platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device, for treating and/or preventing pathological conditions resulting from abnormal cell proliferation; transplantation rejections; autoimmune, inflammatory, proliferative, hyperproliferative or vascular diseases; for reducing scar tissue or for inhibiting wound contraction, particularly the prophylactic and/or therapeutic treatment of restenosis by administering nitrosated and/or nitrosylated rapamycin compounds or rapamycin compounds in combination with nitric oxide donors that are capable of releasing nitric oxide or indirectly delivering or transferring nitric oxide to targeted sites under physiological conditions.

42. 发明申请

WO2004012686A2 NITROSATED AND/OR NITROSYLATED URSODEOXYCHOLIC ACID COMPOUNDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：硝化和/或硝化的乌索二氧甲酸化合物，组合物和使用方法
公开(公告)号：WO2004012686A2
公开(公告)日：2004-02-12
申请号：PCT/US2003/024689
申请日：2003-08-06
申请人： NITROMED, INC. , GARVEY, David, S. , IYENGAR, Radha
发明人： GARVEY, David, S. , IYENGAR, Radha
IPC分类号： A61K
CPC分类号： C07J41/0055
摘要： The invention describes nitrosated and/or nitrosylated ursodeoxycholic acid compounds, or an amide or sulfate conjugate thereof, or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated ursodeoxycholic acid compounds, or an amide or sulfate conjugate thereof, or pharmaceutically acceptable salts thereof, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one ursodeoxycholic acid compound, or an made or sulfate conjugate thereof, or pharmaceutically acceptable salts thereof, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one ursodeoxycholic acid compound, that is optionally nitrosated and/or nitrosylated, and, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating and/or preventing portal hypertension, liver diseases, reflux, gastritis, inflammatory conditions of the gastrointestinal tract, coronary heart diseases, neurological or cognitive conditions or for lowering cholesterol levels.
摘要翻译：本发明描述了亚硝基化和/或亚硝基化的熊去氧胆酸化合物或其酰胺或硫酸盐缀合物或其药学上可接受的盐，以及包含至少一种亚硝基化和/或亚硝基化熊去氧胆酸化合物的新组合物，或其酰胺或硫酸酯缀合物或其药学上可接受的盐，任选地，至少一种捐赠，转移或释放一氧化氮的化合物，刺激一氧化氮的内源性合成，提高内源性内皮水平的内皮衍生的松弛因子，或是一氧化氮合酶，和/或至少一种治疗剂。本发明还提供包含至少一种熊去氧胆酸化合物或其制成或硫酸盐缀合物或其药学上可接受的盐和至少一种捐赠，转移或释放一氧化氮的化合物的新型组合物，其提高内源性内皮水平的内皮衍生的松弛因子刺激一氧化氮的内源性合成或者是一氧化氮合酶和/或至少一种治疗剂的底物。本发明还提供了新颖的试剂盒，其包含至少一种熊去氧胆酸化合物，其任选被亚硝化和/或亚硝基化，并且任选地包含至少一种一氧化氮供体和/或至少一种治疗剂。本发明还提供治疗和/或预防门静脉高压症，肝脏疾病，反流，胃炎，胃肠道炎症，冠心病，神经或认知疾病或降低胆固醇水平的方法。

43. 发明申请

WO2013082000A1 OPSIN-BINDING LIGANDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译： OPSIN-BINDING LIGANDS，COMPOSITIONS AND METHODS OF USE
公开(公告)号：WO2013082000A1
公开(公告)日：2013-06-06
申请号：PCT/US2012/066598
申请日：2012-11-27
申请人： BIKAM PHARMACEUTICALS, INC. , GARVEY, David, S. , GREENWOOD, Jeremy, R. , FRYE, Leah, L.
发明人： GARVEY, David, S. , GREENWOOD, Jeremy, R. , FRYE, Leah, L.
IPC分类号： A61K31/472
CPC分类号： A61K31/472 , C07D217/06 , C07D217/26
摘要： Compounds are disclosed that are useful for treating ophthalmic conditions caused by or related to production of toxic visual cycle products that accumulate in the eye, such as dry adult macular degeneration, as well as conditions caused by or related to the misfolding of mutant opsin proteins and/or the mis-localization of opsin proteins. Compositions of these compounds alone or in combination with other therapeutic agents are also described, along with therapeutic methods of using such compounds and/or compositions. Methods of synthesizing such agents are also disclosed.
摘要翻译：公开的化合物可用于治疗由眼睛中累积的毒性视觉循环产物引起或与其相关的眼部疾病，例如干性成人黄斑变性，以及由突变视蛋白质蛋白质错误折叠引起或与之相关的病症，以及 /或视蛋白蛋白质的错位。还描述了这些化合物单独或与其它治疗剂组合的组合物，以及使用这些化合物和/或组合物的治疗方法。还公开了合成这些试剂的方法。

44. 发明申请

WO2012134971A2 OPSIN-BINDING LIGANDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译： OPSIN-BINDING LIGANDS，COMPOSITIONS AND METHODS OF USE
公开(公告)号：WO2012134971A2
公开(公告)日：2012-10-04
申请号：PCT/US2012/030229
申请日：2012-03-23
申请人： BIKAM PHARMACEUTICALS, INC. , GARVEY, David, S. , LAROSA, Gregory, J. , GREENWOOD, Jeremy, R. , FRYE, Leah, L.
发明人： GARVEY, David, S. , LAROSA, Gregory, J. , GREENWOOD, Jeremy, R. , FRYE, Leah, L.
IPC分类号： A61K31/407
CPC分类号： C07D209/86 , C07C35/38 , C07C35/52 , C07C43/23 , C07C49/675 , C07C49/697 , C07C49/747 , C07C49/755 , C07C251/36 , C07C251/38 , C07C2603/18 , C07D213/30 , C07D307/46 , C07D307/93 , C07D333/16 , C07D333/22 , C07D333/74 , C07D333/78
摘要： Compounds and compositions of said compounds along with methods of use of compounds are disclosed for treating ophthalmic conditions related to mislocalization of opsin proteins, the misfolding of mutant opsin proteins and the production of toxic visual cycle products that accumulate in the eye. Compounds and compositions useful in the these methods, either alone or in combination with other therapeutic agents, are also described, along with methods of use.
摘要翻译：公开了所述化合物的化合物和组合物以及化合物的使用方法，用于治疗与视蛋白蛋白质错位定位相关的眼科疾病，突变视蛋白蛋白质的错误折叠和积聚在眼睛中的毒性视觉循环产物的产生。还描述了可以单独或与其它治疗剂组合的用于这些方法的化合物和组合物，以及使用方法。

45. 发明申请

WO2010147653A1 OPSIN-BINDING LIGANDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译： OPSIN-BINDING LIGANDS，COMPOSITIONS AND METHODS OF USE
公开(公告)号：WO2010147653A1
公开(公告)日：2010-12-23
申请号：PCT/US2010/001739
申请日：2010-06-16
申请人： BIKAM PHARMACEUTICALS, INC. , GARVEY, David, S. , LAROSA, Gregory, J. , GREENWOOD, Jeremy, Robert , BREWER, Mark, L. , QUACH, Tan , COTE, Jamie, B. , BERMAN, Judd
发明人： GARVEY, David, S. , LAROSA, Gregory, J. , GREENWOOD, Jeremy, Robert , BREWER, Mark, L. , QUACH, Tan , COTE, Jamie, B. , BERMAN, Judd
IPC分类号： A01N35/00 , A61K31/11
CPC分类号： C07D295/215 , C07B59/002 , C07B2200/05 , C07C233/10 , C07C275/14 , C07C2601/16 , C07D205/04 , C07D207/12 , C07D207/14 , C07D211/38 , C07D241/04 , C07D241/08 , C07D243/08 , C07D295/182 , C07D295/185 , C07D295/194 , C07D295/205 , C07D295/26 , C07D491/10 , C07D493/08
摘要： Compounds and compositions of said compounds along with methods of use of compounds are disclosed for treating ophthalmic conditions related to mislocalization of opsin proteins, the misfolding of mutant opsin proteins and the production of toxic visual cycle products that accumulate in the eye. Compounds and compositions useful in the these methods, either alone or in combination with other therapeutic agents, are also described.
摘要翻译：公开了所述化合物的化合物和组合物以及化合物的使用方法，用于治疗与视蛋白蛋白质错位定位相关的眼科疾病，突变视蛋白蛋白质的错误折叠以及积聚在眼睛中的毒性视觉循环产物的产生。还描述了可用于这些方法中的单独或与其它治疗剂组合的化合物和组合物。

46. 发明申请

WO2013081642A1 OPSIN-BINDING LIGANDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译： OPSIN-BINDING LIGANDS，COMPOSITIONS AND METHODS OF USE
公开(公告)号：WO2013081642A1
公开(公告)日：2013-06-06
申请号：PCT/US2012/000564
申请日：2012-11-29
申请人： BIKAM PHARMACEUTICALS, INC. , QUACH, Tan , BERMAN, Judd , GARVEY, David, S.
发明人： QUACH, Tan , BERMAN, Judd , GARVEY, David, S.
IPC分类号： A01N35/00
CPC分类号： C07C211/52 , C07C33/50 , C07C43/215 , C07C43/225 , C07C49/237 , C07C49/813 , C07C211/45 , C07C211/46 , C07C217/84 , C07C237/30 , C07C255/54 , C07C255/58 , C07C255/59 , C07C323/09 , C07C2601/10 , C07C2601/14 , C07C2601/16 , C07C2601/18 , C07D317/46 , C07D317/64 , C07D317/66
摘要： Compounds and compositions are disclosed that are useful for treating ophthalmic conditions caused by or related to production of toxic visual cycle products that accumulate in the eye, such as dry adult macular degeneration, as well as conditions caused by or related to the misfolding of mutant opsin proteins and/or the mis-localization of opsin proteins. Compositions of these compounds alone or in combination with other therapeutic agents are also described, along with therapeutic methods of using such compounds and/or compositions. Methods of synthesizing such agents are also disclosed.
摘要翻译：公开的化合物和组合物可用于治疗由于积累在眼睛中的毒性视觉循环产物的产生引起或与之相关的眼部疾病，例如干性成人黄斑变性，以及由突变视蛋白错误折叠引起或与之相关的病症蛋白质和/或视蛋白蛋白质的错误定位。还描述了这些化合物单独或与其它治疗剂组合的组合物，以及使用这些化合物和/或组合物的治疗方法。还公开了合成这些试剂的方法。

47. 发明申请

WO2013058809A1 OPSIN-BINDING LIGANDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译： OPSIN结合配体，组合物和使用方法
公开(公告)号：WO2013058809A1
公开(公告)日：2013-04-25
申请号：PCT/US2012/000522
申请日：2012-10-19
申请人： BIKAM PHARMACEUTICALS, INC. , GARVEY, David, S. , LAROSA, Gregory, J. , GREENWOOD, Jeremy, R. , FRYE, Leah, L. , QUACH, Tan , COTE, Jamie, B. , BERMAN, Judd
发明人： GARVEY, David, S. , LAROSA, Gregory, J. , GREENWOOD, Jeremy, R. , FRYE, Leah, L. , QUACH, Tan , COTE, Jamie, B. , BERMAN, Judd
IPC分类号： A01N43/38
CPC分类号： C07D307/83 , C07C35/32 , C07C49/443 , C07C49/553 , C07C69/75 , C07C233/58 , C07C251/44 , C07C2102/24 , C07D209/34 , C07D209/46
摘要： Compounds are disclosed that are useful for treating ophthalmic conditions caused by or related to production of toxic visual cycle products that accumulate in the eye, such as dry adult macular degeneration, as well as conditions caused by or related to the misfolding of mutant opsin proteins and/or the mis-localization of opsin proteins. Compositions of these compounds alone or in combination with other therapeutic agents are also described, along with therapeutic methods of using such compounds and/or compositions. Methods of synthesizing such agents are also disclosed.
摘要翻译：公开了用于治疗由眼部积聚的有毒视觉循环产物引起的或与眼部产生有关的眼科疾病的化合物，例如干性成人黄斑变性，以及由或由其引起的疾病涉及突变视蛋白的错误折叠和/或视蛋白蛋白的错误定位。还描述了单独或与其他治疗剂组合的这些化合物的组合物以及使用这些化合物和/或组合物的治疗方法。还公开了合成这些试剂的方法。

48. 发明申请

WO2011155983A1 OPSIN-BINDING LIGANDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译： OPSIN-BINDING LIGANDS，COMPOSITIONS AND METHODS OF USE
公开(公告)号：WO2011155983A1
公开(公告)日：2011-12-15
申请号：PCT/US2011/001028
申请日：2011-06-07
申请人： BIKAM PHARMACEUTICALS INC. , GARVEY, David, S. , LAROSA, Gregory, J. , GREENWOOD, Jeremy, R. , FRYE, Leah, L.
发明人： GARVEY, David, S. , LAROSA, Gregory, J. , GREENWOOD, Jeremy, R. , FRYE, Leah, L.
IPC分类号： A61K31/015 , A01N43/38
CPC分类号： C07D333/78 , C07B2200/05 , C07C13/28 , C07C13/567 , C07C25/22 , C07C35/52 , C07C43/168 , C07C43/176 , C07C49/697 , C07C49/798 , C07C49/813 , C07C251/48 , C07C255/53 , C07C255/56 , C07C309/65 , C07C2601/08 , C07C2601/14 , C07C2601/16 , C07C2603/18 , C07D209/88
摘要： Compounds are disclosed that are useful for treating ophthalmic conditions related to mislocalization of opsin proteins, the misfolding of mutant opsin proteins and the production of toxic visual cycle products that accumulate in the eye. Compositions of these compounds, either alone or in combination with other therapeutic agents, are also disclosed, along with thereapeutic methods of using such compositions. Methods of synthesizing such compounds are also described.
摘要翻译：公开了可用于治疗与视蛋白蛋白质错位定位相关的眼科疾病，突变视蛋白蛋白错误折叠以及积聚在眼睛中的毒性视觉循环产物的产生的化合物。单独或与其它治疗剂组合的这些化合物的组合物，以及使用这些组合物的治疗方法也被公开。还描述了合成这些化合物的方法。

49. 发明申请

WO2010074746A1 METHODS OF USE FOR OPSIN BINDING LIGANDS 审中-公开
标题翻译：用于OPSIN绑定配偶的方法
公开(公告)号：WO2010074746A1
公开(公告)日：2010-07-01
申请号：PCT/US2009/006668
申请日：2009-12-22
申请人： BIKAM PHARMACEUTICALS, INC. , GARVEY, David, S. , LAROSA, Gregory, J. , GREENWOOD, Jeremy Robert , WATTS, Karl, Shawn , FRYE, Leah, Lynn , FARID, Ramy, Samir
发明人： GARVEY, David, S. , LAROSA, Gregory, J. , GREENWOOD, Jeremy Robert , WATTS, Karl, Shawn , FRYE, Leah, Lynn , FARID, Ramy, Samir
IPC分类号： A01N57/00 , A61K31/675
CPC分类号： A61K31/675
摘要： Methods of use of compounds of the Formula I1 II, III, IV and/or V are disclosed for treating ophthalmic conditions related to the production of toxic visual cycle products that accumulate in the eye, and are associated with reactions of the visual cycle during medical procedures that expose the eye to light, most commonly the various forms of ophthalmic surgery and stabilize the proper folding of mutant opsins. Compounds and compositions useful in the these methods, either alone or in combination with other therapeutic agents, are also described, along with methods of screening for new agents useful in said treatments.
摘要翻译：公开了使用式IIII，III，IV和/或V化合物的方法用于治疗与积累在眼睛中的毒性视觉循环产物的生产有关的眼科疾病，并且与医学期间的视觉循环的反应相关使眼睛光亮的程序，最常见的是各种形式的眼科手术，并稳定突变蛋白的正确折叠。还描述了用于这些方法的化合物和组合物，单独或与其它治疗剂组合，以及筛选可用于所述治疗的新试剂的方法。

50. 发明申请

WO2012174064A1 OPSIN-BINDING LIGANDS, COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译： OPSIN-BINDING LIGANDS，COMPOSITIONS AND METHODS OF USE
公开(公告)号：WO2012174064A1
公开(公告)日：2012-12-20
申请号：PCT/US2012/042178
申请日：2012-06-13
申请人： BIKAM PHARMACEUTICALS, INC. , GARVEY, David, S.
发明人： GARVEY, David, S.
IPC分类号： A01N35/00
CPC分类号： C07D333/22 , A61K31/045 , A61K31/12 , A61K31/277 , C07C25/06 , C07C25/13 , C07C25/18 , C07C33/14 , C07C33/34 , C07C33/50 , C07C43/23 , C07C49/792 , C07C49/813 , C07C49/84 , C07C255/53 , C07C255/56 , C07C259/18 , C07C2601/14 , C07C2601/16 , C07D307/42 , C07D307/46 , C07D333/16
摘要： Compounds are disclosed that are useful for treating ophthalmic conditions caused by or related to production of toxic visual cycle products that accumulate in the eye, such as dry adult macular degeneration, as well as conditions caused by or related to the misfolding of mutant opsin proteins and/or the mis-localization of opsin proteins. Compositions of these compounds alone or in combination with other therapeutic agents are also described, along with therapeutic methods of using such compounds and/or compositions. Methods of synthesizing such agents are also disclosed.
摘要翻译：公开的化合物可用于治疗由眼睛中累积的毒性视觉循环产物引起或与其相关的眼部疾病，例如干性成人黄斑变性，以及由突变视蛋白质蛋白质错误折叠引起或与之相关的病症，以及 /或视蛋白蛋白质的错位。还描述了这些化合物单独或与其它治疗剂组合的组合物，以及使用这些化合物和/或组合物的治疗方法。还公开了合成这些试剂的方法。

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