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1. 发明申请

US20130123175A1 Compounds for Delivery of Therapeutic And Imaging Moieties to Nerve Cells 审中-公开
标题翻译：用于向神经细胞递送治疗和成像部位的化合物
公开(公告)号：US20130123175A1
公开(公告)日：2013-05-16
申请号：US13535187
申请日：2012-06-27
申请人： G. Craig Hill , Stephen B. Kahl , Robert R. Webb , Constance A. McKee
发明人： G. Craig Hill , Stephen B. Kahl , Robert R. Webb , Constance A. McKee
IPC分类号： C07K14/48
CPC分类号： C07K14/48 , A61K47/6425 , A61K47/6807
摘要： The invention features compounds of the general formula: B-L-M where B is a binding agent capable of selectively binding to a nerve cell surface receptor and mediating absorption of the compound by the nerve cell; M is a moiety which performs a useful non-cytotoxic function when absorbed by a nerve cell, and can be a therapeutic moiety or an imaging moiety; and L is a linker coupling B to M. The invention also features methods of use of the compounds in, for example, treating conditions such as viral infections and pain, as well as in labeling nerve cells.
摘要翻译：本发明具有以下通式的化合物：B-L-M其中B是能够选择性结合神经细胞表面受体并介导神经细胞吸收化合物的结合剂; M是当被神经细胞吸收时可以执行有用的非细胞毒性功能的部分，并且可以是治疗部分或成像部分; 并且L是将B连接到M的接头。本发明还涉及在例如治疗病症如病毒感染和疼痛以及标记神经细胞中的化合物的使用方法。

2. 发明授权

US08232251B2 Compounds for delivery of therapeutic and imaging moieties to nerve cells 有权
标题翻译：用于将治疗和成像部分递送至神经细胞的化合物
公开(公告)号：US08232251B2
公开(公告)日：2012-07-31
申请号：US12323421
申请日：2008-11-25
申请人： G. Craig Hill , Stephen B. Kahl , Robert R. Webb , Constance A. McKee
发明人： G. Craig Hill , Stephen B. Kahl , Robert R. Webb , Constance A. McKee
IPC分类号： A61K38/16 , A61K47/28
CPC分类号： C07K14/48 , A61K47/6425 , A61K47/6807
摘要： The invention features compounds of the general formula: B-L-M where B is a binding agent capable of selectively binding to a nerve cell surface receptor and mediating absorption of the compound by the nerve cell; M is a moiety which performs a useful non-cytotoxic function when absorbed by a nerve cell, and can be a therapeutic moiety or an imaging moiety; and L is a linker coupling B to M. The invention also features methods of use of the compounds in, for example, treating conditions such as viral infections and pain, as well as in labeling nerve cells.
摘要翻译：本发明具有以下通式的化合物：B-L-M其中B是能够选择性结合神经细胞表面受体并介导神经细胞吸收化合物的结合剂; M是当被神经细胞吸收时可以执行有用的非细胞毒性功能的部分，并且可以是治疗部分或成像部分; 并且L是将B连接到M的接头。本发明还涉及在例如治疗病症如病毒感染和疼痛以及标记神经细胞中的化合物的使用方法。

3. 发明申请

US20090286732A1 COMPOUNDS FOR DELIVERY OF THERAPEUTIC AND IMAGING MOIETIES TO NERVE CELLS 有权
标题翻译：用于将治疗和成像感染输送到神经细胞的化合物
公开(公告)号：US20090286732A1
公开(公告)日：2009-11-19
申请号：US12323421
申请日：2008-11-25
申请人： Gordon Craig Hill , Stephen B. Kahl , Robert R. Webb , Constance A. McKee
发明人： Gordon Craig Hill , Stephen B. Kahl , Robert R. Webb , Constance A. McKee
IPC分类号： A61K38/18 , C07K14/475 , A61P25/00
CPC分类号： C07K14/48 , A61K47/6425 , A61K47/6807
摘要： The invention features compounds of the general formula: B-L-M where B is a binding agent capable of selectively binding to a nerve cell surface receptor and mediating absorption of the compound by the nerve cell; M is a moiety which performs a useful non-cytotoxic function when absorbed by a nerve cell, and can be a therapeutic moiety or an imaging moiety; and L is a linker coupling B to M. The invention also features methods of use of the compounds in, for example, treating conditions such as viral infections and pain, as well as in labeling nerve cells.
摘要翻译：本发明具有以下通式的化合物：B-L-M其中B是能够选择性结合神经细胞表面受体并介导神经细胞吸收化合物的结合剂; M是当被神经细胞吸收时可以执行有用的非细胞毒性功能的部分，并且可以是治疗部分或成像部分; 并且L是将B连接到M的接头。本发明还涉及在例如治疗病症如病毒感染和疼痛以及标记神经细胞中的化合物的使用方法。

4. 发明授权

US06887861B1 Compounds for intracellular delivery of therapeutic moieties to nerve cells 有权
标题翻译：将治疗性部分细胞内递送给神经细胞的化合物
公开(公告)号：US06887861B1
公开(公告)日：2005-05-03
申请号：US09707730
申请日：2000-11-06
申请人： Gordon Craig Hill , Stephen B. Kahl , Robert R. Webb , Constance A. McKee
发明人： Gordon Craig Hill , Stephen B. Kahl , Robert R. Webb , Constance A. McKee
IPC分类号： A61K47/30 , A61K47/42 , A61K47/48 , A61P5/00 , A61P25/00 , A61P25/04 , A61P31/12 , A81K31/56 , A61M36/14 , G01N33/00 , A81K31/58 , A81K51/00
CPC分类号： A61K47/6807 , A61K47/6425 , Y10T436/21
摘要： A method for improving intracellular administration of a therapeutic agent is provided comprising: contacting cells with a compound comprising a charged derivative of a therapeutic agent having a therapeutic activity, the charged derivative being conjugated to a protein having a biological activity of being transported across a cell membrane into a cell; and having the cell transport the compound into the cell where the cell metabolizes at least a portion of the compound to form a charged metabolite product that possesses the therapeutic activity of the therapeutic agent, the charged metabolite product being less prone to being transported across the cell membrane out of the cell relative to the compound and less prone to being transported across the cell membrane out of the cell relative to the therapeutic agent.
摘要翻译：提供了一种用于改善细胞内施用治疗剂的方法，其包括：使细胞与包含具有治疗活性的治疗剂的带电荷的衍生物的化合物接触，所述带电荷的衍生物与具有生物活性的蛋白质缀合，膜成细胞; 并且使细胞将化合物转运到细胞中，其中细胞代谢化合物的至少一部分以形成具有治疗剂的治疗活性的带电代谢产物，所加入的代谢产物不太容易被传输通过细胞膜相对于化合物离开细胞，并且相对于治疗剂不太容易被传送通过细胞膜离开细胞。

5. 发明授权

US5654423A Boronated metalloporphyrine and therapeutic methods 失效
标题翻译：硼化金属卟啉和治疗方法
公开(公告)号：US5654423A
公开(公告)日：1997-08-05
申请号：US448225
申请日：1995-05-23
申请人： Stephen B. Kahl , Myoung-Seo Koo
发明人： Stephen B. Kahl , Myoung-Seo Koo
IPC分类号： C07F5/02 , C07F5/05 , C07D487/22
CPC分类号： B82Y5/00 , C07F5/027 , C07F5/05
摘要： Carborane substituted porphyrin compounds complexed with a metal or transition metal have a variety of therapeutic uses. These compounds have been found, for example, selectively to inhibit viral aspartyl proteases. The transition metal complexes are useful both therapeutically in BNCT (boron neutron capture therapy) as well as for MR contrast enhancement. Particularly preferred compounds in accordance with the invention use the dipotassium salt of 2,4-bis-[.alpha.,.beta.-(1,2-dicarbaclosododecaborane carboxy)ethyl]deuteroporphyrin, which is complexed with a metal or a transition metal. These compounds are well solubilized in water, and are suitable for oral administration.
摘要翻译：与金属或过渡金属络合的碳硼烷取代的卟啉化合物具有多种治疗用途。已经发现这些化合物例如选择性地抑制病毒天冬氨酰蛋白酶。过渡金属络合物在治疗上可用于BNCT（硼中子俘获治疗）以及MR对比度增强。根据本发明的特别优选的化合物使用与金属或过渡金属络合的2,4-双 - [α，β-（1,2-二十二碳十二碳十二烷羧基）乙基]氘卟啉的二钾盐。这些化合物很好地溶于水，适合于口服给药。

6. 发明授权

US5284831A Drug delivery porphyrin compositions and methods 失效
标题翻译：药物输送卟啉组合物和方法
公开(公告)号：US5284831A
公开(公告)日：1994-02-08
申请号：US869611
申请日：1992-04-16
申请人： Stephen B. Kahl , Myoung-Seo Koo
发明人： Stephen B. Kahl , Myoung-Seo Koo
IPC分类号： A61K31/69 , A61K9/127 , A61K41/00 , A61K49/00 , A61K51/00 , A61K51/04 , A61P35/00 , C07F5/02 , C07F5/05 , A61K31/40 , A61K37/00 , C07D487/22 , C07K15/16
CPC分类号： A61K51/0485 , A61K41/0071 , A61K41/0095 , A61K47/48069 , A61K9/1275 , C07F5/027 , C07F5/05 , A61K2121/00
摘要： A compound is described having the structure (* CHEMICAL STRUCTURE *) where R preferably is (* CHEMICAL STRUCTURE *) and most preferably R3 is a closo-carborane and R2 is -H, an alkyl or aryl having 1 to about 7 carbon atoms, or a physiologically acceptable salt. Compounds of the invention are useful in boron neutron capture therapy, photodynamic therapy, and other biomedical applications. One embodiment we have designated 2,4-bis-((alpha),(beta)-(1,2-dicarbaclosododecaborane carboxy) ethyl)deuteroporphyrin (x), appears not to pass through the normal blood brain barrier, has excellent water solubility, and has been shown efficacious in boron neutron capture therapy in vivo against the KHJJ mammary carcinoma.
摘要翻译：描述了具有结构的化合物，其中R优选为“IMAGE”，最优选R3为氯代碳硼烷，R2为-H，具有1至约7个碳原子的烷基或芳基或生理学上可接受的盐。本发明的化合物可用于硼中子俘获治疗，光动力疗法和其它生物医学应用。一个实施方案，我们已经指定了2,4-双 - [α，β-（1,2-二十二烷基十二碳代碳原子羧基）乙基]氘卟啉（x），似乎不通过正常的血脑屏障，具有优异的水溶性，并且已经显示在体内对KHJJ乳腺癌的硼中子捕获治疗有效。

7. 发明授权

US5149801A Boronated porphyrin compounds 失效
标题翻译：硼氢化卟啉化合物
公开(公告)号：US5149801A
公开(公告)日：1992-09-22
申请号：US616679
申请日：1990-11-21
申请人： Stephen B. Kahl , Myoung-Seo Koo
发明人： Stephen B. Kahl , Myoung-Seo Koo
IPC分类号： A61K31/69 , A61K9/127 , A61K41/00 , A61K49/00 , A61K51/00 , A61K51/04 , A61P35/00 , C07F5/02 , C07F5/05
CPC分类号： A61K51/0485 , A61K41/0071 , A61K41/0095 , A61K47/48069 , A61K9/1275 , C07F5/027 , C07F5/05 , A61K2121/00
摘要： A compound is described having the structure ##STR1## where R preferably is ##STR2## and most preferably R.sup.3 is a closo-carborane and R.sup.2 is --H, an alkyl or aryl having 1 to about 7 carbon atoms,This invention was made with Government support under NIH Grant No. CA-37961 awarded by the Department of Health and Human Services and under the Associated Universities Inc. Contract No. De-AC02-76CH00016 with the U.S. Department of Energy. The Government has rights in this invention.
摘要翻译：描述了具有结构的化合物，其中R优选为“IMAGE”，最优选R3为氯代碳硼烷，R2为-H，具有1至约7个碳原子的烷基或芳基或生理学上可接受的盐。本发明的化合物可用于硼中子俘获治疗，光动力疗法和其它生物医学应用。一个实施方案，我们已经指定了2,4-双 - [α，β-（1,2-二十二烷基十二碳代碳原子羧基）乙基]氘卟啉（x），似乎不通过正常的血脑屏障，具有优异的水溶性，并且已经显示在体内对KHJJ乳腺癌的硼中子捕获治疗有效。

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