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1. 发明申请

WO2008067002A8 AZOLE NUCLEOSIDES AND USE AS INHIBITORS OF RNA AND DNA VARIAL POLYMERASES 审中-公开
标题翻译： AZOLE核苷及其作为RNA和DNA变异聚合物的抑制剂的应用
公开(公告)号：WO2008067002A8
公开(公告)日：2008-09-12
申请号：PCT/US2007078139
申请日：2007-09-11
申请人： SOUTHERN RES INST , UNIV NEW MEXICO , ARTERBURN JEFFREY B , JONSSON COLLEEN B , PARKER WILLIAM B
发明人： ARTERBURN JEFFREY B , JONSSON COLLEEN B , PARKER WILLIAM B
IPC分类号： A01N43/04 , A61K31/70 , C07H5/04 , C07H5/06 , C07H19/044 , C07H19/056
CPC分类号： C07H5/04 , C07H5/06 , C07H19/044 , C07H19/056
摘要： Azole nucleosides represented by the formulae (I) and (II); wherein A = C or N B = C or N X = H; C 1 -C 6 alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, heterocyclo, halogen such as F, C1, Br and I; OH, NH 2 , NH-(C 1 -C 6 alkyl, cycloalkyl, aryl, or heterocyclo); Z = H; C 1 -C 6 alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, heterocyclo, halogen such as F, Cl, Br, I; OH, NH 2 , NH-(C 1 -C 6 alkyl, cycloalkyl, aryl, or heterocyclo; E= (CH 2 )HONHR 1 ; n is an integer from 0-6 and more typically 0-3; R 1 = aryl or heterocyclo; each of W, Y, R is individually selected from the group consisting of H; C 1 -C 6 alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, heterocyclo; halogen such as F, Cl, Br, and I; O, OH, Oalkyl, Oaryl, NH 2 , NH-(C 1 -C 6 alkyl, cycloalkyl, aryl, or heterocyclo); provided that at least one of W, Y, and R is other than H and wherein both W and Y together can be =O; and each D individually is OH, Oalkyl, Oaryl, Fl and H;pharmaceutically acceptable salts thereof, prodrugs thereof and mixtures thereof are provided. Compounds of this disclosure are useful as inhibitors of viral RNA and DNA polymerases such as, but not limited to, Influenza, Hantaan Virus, Crimean Congo hemorrhagic fever virus, hepatitis B, hepatitis C, Polio, Coxsackie A and B, Rhino, Echo, orthopoxvirus (small pox), HIV, Ebola, and West Nile virus polymerases; and especially orthopoxvirus, HIV, and hepatitis B.
摘要翻译：由式（I）和（II）表示的唑核苷; 其中A = C或N B = C或N X = H; C 1-6烷基，环烷基，链烯基，环烯基，炔基，芳基，杂环基，卤素如F，Cl，Br和I; OH，NH 2，NH-（C 1 -C 6烷基，环烷基，芳基或杂环）。 Z = H; C 1-6烷基，环烷基，烯基，环烯基，炔基，芳基，杂环基，卤素如F，Cl，Br，I; OH，NH 2，NH-（C 1 -C 6）烷基，环烷基，芳基或杂环; E =（CH 2） 2）HONHR 1 1; n是0-6的整数，更典型的是0-3; R 1 =芳基或杂环; W，Y R独立地选自H，C 1 -C 6烷基，环烷基，烯基，环烯基，炔基，芳基，杂环基;卤素如F， Cl，Br和I; O，OH，O烷基，O芳基，NH 2，NH-（C 1 -C 6烷基，环烷基，芳基或杂环）;条件是W，Y和R中的至少一个不是H，并且其中W和Y一起可以是= O;并且每个D独立地是OH，O烷基，O芳基，F1和H; 本公开的化合物可用作病毒RNA和DNA聚合酶的抑制剂，例如但不限于流感病毒，汉坦病毒，克里米亚刚果出血热病毒，乙型肝炎，肝炎 C，小儿麻痹症，柯萨奇A和B，犀牛，回声，正痘病毒（小痘），HIV，埃博拉病毒和西尼罗河病毒聚合酶; 特别是正痘病毒，艾滋病毒和乙型肝炎。

2. 发明申请

WO2008067002A3 AZOLE NUCLEOSIDES AND USE AS INHIBITORS OF RNA AND DNA VARIAL POLYMERASES 审中-公开
标题翻译：单核苷酸和用作RNA和DNA多肽的抑制剂
公开(公告)号：WO2008067002A3
公开(公告)日：2008-11-06
申请号：PCT/US2007078139
申请日：2007-09-11
申请人： SOUTHERN RES INST , UNIV NEW MEXICO , ARTERBURN JEFFREY B , JONSSON COLLEEN B , PARKER WILLIAM B
发明人： ARTERBURN JEFFREY B , JONSSON COLLEEN B , PARKER WILLIAM B
IPC分类号： A01N43/04 , A61K31/70 , C07H5/04 , C07H5/06 , C07H19/044 , C07H19/056
CPC分类号： C07H5/04 , C07H5/06 , C07H19/044 , C07H19/056
摘要： Azole nucleosides represented by the formulae (I) and (II); wherein A = C or N B = C or N X = H; C 1 -C 6 alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, heterocyclo, halogen such as F, C1, Br and I; OH, NH 2 , NH-(C 1 -C 6 alkyl, cycloalkyl, aryl, or heterocyclo); Z = H; C 1 -C 6 alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, heterocyclo, halogen such as F, Cl, Br, I; OH, NH 2 , NH-(C 1 -C 6 alkyl, cycloalkyl, aryl, or heterocyclo; E= (CH 2 )HONHR 1 ; n is an integer from 0-6 and more typically 0-3; R 1 = aryl or heterocyclo; each of W, Y, R is individually selected from the group consisting of H; C 1 -C 6 alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, heterocyclo; halogen such as F, Cl, Br, and I; O, OH, Oalkyl, Oaryl, NH 2 , NH-(C 1 -C 6 alkyl, cycloalkyl, aryl, or heterocyclo); provided that at least one of W, Y, and R is other than H and wherein both W and Y together can be =O; and each D individually is OH, Oalkyl, Oaryl, Fl and H;pharmaceutically acceptable salts thereof, prodrugs thereof and mixtures thereof are provided. Compounds of this disclosure are useful as inhibitors of viral RNA and DNA polymerases such as, but not limited to, Influenza, Hantaan Virus, Crimean Congo hemorrhagic fever virus, hepatitis B, hepatitis C, Polio, Coxsackie A and B, Rhino, Echo, orthopoxvirus (small pox), HIV, Ebola, and West Nile virus polymerases; and especially orthopoxvirus, HIV, and hepatitis B.
摘要翻译：由式（I）和（II）表示的唑类核苷; 其中A = C或N B = C或N X = H; C 1 -C 6烷基，环烷基，烯基，环烯基，炔基，芳基，杂环基，卤素如F，Cl，Br和I; OH，NH 2，NH-（C 1 -C 6烷基，环烷基，芳基或杂环）; Z = H; C 1 -C 6烷基，环烷基，烯基，环烯基，炔基，芳基，杂环基，卤素如F，Cl，Br，I; OH，NH 2，NH-（C 1 -C 6烷基，环烷基，芳基或杂环; E =（CH 3） 2 HONHR 1; n是0-6，更典型地0-3的整数; R 1 =芳基或杂环; W，Y R 1独立地选自H; C 1 -C 6烷基，环烷基，烯基，环烯基，炔基，芳基，杂环;卤素如F， Cl，Br和I; O，OH，O烷基，芳基，NH 2，NH-（C 1 -C 6烷基，环烷基，芳基或杂环基）;条件是W，Y和R中的至少一个不是H，并且其中W和Y一起可以是= O;并且每个D分别是OH，O烷基，芳基，F 1和H; 本公开的化合物可用作病毒RNA和DNA聚合酶的抑制剂，例如但不限于流感，汉坦病毒，克里米亚刚果出血热病毒，乙型肝炎，肝炎 C，脊髓灰质炎，柯萨奇A和B，犀牛，回声，正痘病毒（小痘），HIV，埃博拉和西尼罗病毒聚合酶; 尤其是正痘病毒，艾滋病毒和乙型肝炎。

3. 发明申请

WO2010019954A2 PURINE NUCLEOSIDE PHOSPHORYLASE AS ENZYMATIC ACTIVATOR OF NUCLEOSIDE PRODRUGS 审中-公开
标题翻译：磷酸核苷酸磷酸酶作为核苷酸酶的酶促活化剂
公开(公告)号：WO2010019954A2
公开(公告)日：2010-02-18
申请号：PCT/US2009054058
申请日：2009-08-17
申请人： UAB RESEARCH FOUNDATION , SOUTHERN RES INST , PARKER WILLIAM B , SORSCHER ERIC J
发明人： PARKER WILLIAM B , SORSCHER ERIC J
IPC分类号： A61K38/43 , A61K39/21 , A61P35/00
CPC分类号： A61K38/45 , A61K31/7076 , A61K35/12 , A61K48/00 , A61K48/005 , C12N9/1077 , C12N2799/022 , C12N2799/027 , C12N2799/04 , C12P17/182 , C12Y204/02001 , A61K2300/00
摘要： A process for inhibiting a mammalian cancerous cell or virally infected cell includes providing a Trichomonas vaginalis purine nucleoside phosphorylase enzyme or a tail mutant purine nucleoside phosphorylase enzyme in proximity to the mammalian cancerous cell or the virally infected cell and exposing the enzyme to a purine nucleoside phosphorylase enzyme cleavable substrate to yield a cytotoxic purine analog. The process includes introducing to the cell a vector containing the phosphorylase enzyme, or a DNA sequence coding for the same and delivering to the cell an effective amount of the substrate such as 9-(ß-D-arabinofuranosyl)-2- fluoroadenine (F-araA).
摘要翻译：抑制哺乳动物癌细胞或病毒感染细胞的方法包括在哺乳动物癌细胞或病毒感染细胞附近提供阴道毛滴虫嘌呤核苷磷酸化酶或尾突变体嘌呤核苷磷酸化酶，并将该酶暴露于嘌呤核苷磷酸化酶酶切割底物产生细胞毒性嘌呤类似物。该方法包括向细胞中引入含有磷酸化酶的载体或编码该载体的DNA序列，并向细胞递送有效量的底物，例如9-（ß-D-阿拉伯呋喃糖基）-2-氟腺嘌呤（F -araA）。

4. 发明申请

WO2010019954A9 PURINE NUCLEOSIDE PHOSPHORYLASE AS ENZYMATIC ACTIVATOR OF NUCLEOSIDE PRODRUGS 审中-公开
标题翻译：嘌呤核苷磷酸化酶作为核苷酸前药的酶促激活剂
公开(公告)号：WO2010019954A9
公开(公告)日：2010-08-12
申请号：PCT/US2009054058
申请日：2009-08-17
申请人： UAB RESEARCH FOUNDATION , SOUTHERN RES INST , PARKER WILLIAM B , SORSCHER ERIC J
发明人： PARKER WILLIAM B , SORSCHER ERIC J
IPC分类号： A61K38/43 , A61K39/21 , A61P35/00
CPC分类号： A61K38/45 , A61K31/7076 , A61K35/12 , A61K48/00 , A61K48/005 , C12N9/1077 , C12N2799/022 , C12N2799/027 , C12N2799/04 , C12P17/182 , C12Y204/02001 , A61K2300/00
摘要： A process for inhibiting a mammalian cancerous cell or virally infected cell includes providing a Trichomonas vaginalis purine nucleoside phosphorylase enzyme or a tail mutant purine nucleoside phosphorylase enzyme in proximity to the mammalian cancerous cell or the virally infected cell and exposing the enzyme to a purine nucleoside phosphorylase enzyme cleavable substrate to yield a cytotoxic purine analog. The process includes introducing to the cell a vector containing the phosphorylase enzyme, or a DNA sequence coding for the same and delivering to the cell an effective amount of the substrate such as 9-(ß-D-arabinofuranosyl)-2- fluoroadenine (F-araA).
摘要翻译：抑制哺乳动物癌细胞或病毒感染细胞的方法包括在哺乳动物癌细胞或病毒感染细胞附近提供阴道毛滴虫嘌呤核苷磷酸化酶或尾突变嘌呤核苷磷酸化酶，并将该酶暴露于嘌呤核苷磷酸化酶酶可切割底物以产生细胞毒性嘌呤类似物。该方法包括向细胞中导入含有磷酸化酶的载体或编码该载体的DNA序列，并将有效量的底物如9-（β-D-阿拉伯呋喃糖基）-2-氟腺嘌呤（F -araA）。

5. 发明申请

WO2012112984A2 ENHANCED THERAPEUTIC USAGE OF A PURINE NUCLEOSIDE PHOSPHORYLASE OR NUCLEOSIDE HYDROLASE PRODRUG RELATED APPLICATIONS 审中-公开
标题翻译：嘌呤核苷酸磷酸酶或核苷酸水解酶的增强治疗应用相关应用
公开(公告)号：WO2012112984A2
公开(公告)日：2012-08-23
申请号：PCT/US2012025816
申请日：2012-02-20
申请人： UAB RESEARCH FOUNDATION , SOUTHERN RES INST , PARKER WILLIAM B , SORSCHER ERIC J
发明人： PARKER WILLIAM B , SORSCHER ERIC J
CPC分类号： A61K38/47 , A61K9/06 , A61K9/1641 , A61K9/1647 , A61K31/7076 , A61K38/45 , A61K38/465 , A61K48/00 , A61K2300/00
摘要： The use of a purine nucleoside phosphorylase or nucleoside hydrolase or a vector encoding expression of one of these enzymes is detailed along with the use of a prodrug cleaved by the purine nucleoside phosphorylase or nucleoside hydrolase for the preparation of a direct injection inhibition of replicating or non-replicating targeted cells. The targeted cells do not normally express the introduced purine nucleoside phosphorylase or nucleoside hydrolase. The enzyme and prodrug are amenable to intermixing and injection as a single dose or as separate injection or administration to the targeted cells. The substance and prodrug efficacy are enhanced through exposure of the targeted cells to X-ray radiation. Administration of a prodrug regardless of administration route to the targeted cells is effective in combination with X-ray radiation therapy to kill or inhibit function of the targeted cells.
摘要翻译：使用嘌呤核苷磷酸化酶或核苷水解酶或编码这些酶之一的载体的载体以及由嘌呤核苷磷酸化酶或核苷水解酶切割的前体药物的用途，用于制备直接注射抑制复制或非 - - 复制靶细胞。目标细胞通常不表达引入的嘌呤核苷磷酸化酶或核苷水解酶。酶和前药可以作为单一剂量混合和注射，或者作为单独的注射或给予靶细胞。通过将靶细胞暴露于X射线辐射来增强物质和前药功效。无论向目标细胞的施用途径如何，前药的施用与X射线辐射治疗组合是有效的，以杀死或抑制靶细胞的功能。

6. 发明申请

WO02088323A3 GENE DELIVERY COMPOUNDS 审中-公开
标题翻译：基因递送化合物
公开(公告)号：WO02088323A3
公开(公告)日：2003-02-20
申请号：PCT/US0213895
申请日：2002-05-02
申请人： UAB RESEARCH FOUNDATION , SOUTHERN RES INST , SORSCHER ERIC J , HONG JEONG S , HARRIS JENNIFER E , CURLEE KIMBERLY V , MADDRY JOSEPH A , PARKER WILLIAM B , WAUD WILLIAM R
发明人： SORSCHER ERIC J , HONG JEONG S , HARRIS JENNIFER E , CURLEE KIMBERLY V , MADDRY JOSEPH A , PARKER WILLIAM B , WAUD WILLIAM R
IPC分类号： A61K31/15 , A61K31/7076 , A61K45/06 , A61K48/00 , C07D213/53 , C12N15/87 , A61K31/33
CPC分类号： C07D213/53 , A61K31/15 , A61K31/7076 , A61K45/06 , A61K48/0008 , A61K2300/00
摘要： Compounds having the structure (I) wherein R1, R2 and R3 are each independently a CO-12 substituent selected from the group consisting of: hydrogen, a heteroatom, alkyl, alkenyl, alkynyl, heteroatom substituted alkyl, heteroatom substituted alkenyl, heteroatom substituted alkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl; where the heteroatom is selected from the group consisting of: N, O and S; and where (A) is a single or double bond between N and R3. Further the CO-12 substituent is linear, branched or cyclic and optionally includes a pendant moiety selected from the group consisting of: carbonyl, hydroxyl, carboxyl, amine, thiol, thioester, thioether, phosphate, alkoxy, aryl, arylalkyl, sulfonamide and alkyl halide. Further, compounds (6883, 6898, 6975, 7036, 7064 and 8496) are provided. A process is provided for activating gene transfer in a subject by administering a pharmaceutically effective amount of a gene transfer activating compound to a subject and delivering pharmaceutically effective amount of a vector containing a nucleic so that the nucleic acid is transcribed in a target cell of the subject. A process for activating gene transfer to a cell is provided. A kit for activating gene transfer is provided.
摘要翻译：具有结构（I）的化合物，其中R 1，R 2和R 3各自独立地是选自以下的CO-12取代基：氢，杂原子，烷基，烯基，炔基，杂原子取代的烷基，杂原子取代的烯基，杂原子取代的炔基，芳基，芳基烷基，芳基烯基，芳基炔基; 其中杂原子选自：N，O和S; 其中（A）是N和R3之间的单键或双键。此外，CO-12取代基是直链，支链或环状的，并且任选地包括选自羰基，羟基，羧基，胺，硫醇，硫酯，硫醚，磷酸酯，烷氧基，芳基，芳基烷基，磺酰胺和烷基卤化物。此外，提供了化合物（6883,6898,6975,7036,7064和8496）。提供了通过向受试者施用药学有效量的基因转移活化化合物并递送药学有效量的含有核酸的载体以使得核酸被转录到靶细胞的靶细胞中来激活受试者中的基因转移的方法学科。提供了一种激活基因转移至细胞的方法。提供用于激活基因转移的试剂盒。

7. 发明申请

WO9507718A3 PURINE NUCLEOSIDE PHOSPHORYLASE GENE THERAPY FOR HUMAN MALIGNANCY 审中-公开
标题翻译：嘌呤核苷酸磷酸酶基因治疗人类恶性肿瘤
公开(公告)号：WO9507718A3
公开(公告)日：1995-04-13
申请号：PCT/US9410130
申请日：1994-09-14
申请人： UAB RESEARCH FOUNDATION , SOUTHERN RES INST
发明人： SORSCHER ERIC J , PARKER WILLIAM B , BENNETT LEONARD L JR
IPC分类号： C12N15/09 , A61K9/127 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/7076 , A61K38/45 , A61K39/395 , A61K47/48 , A61K48/00 , A61P31/12 , A61P35/00 , C07H19/16 , C07H21/04 , C12N9/10 , C12N15/54 , C12Q1/48 , A61K38/46 , A61K47/42
CPC分类号： B82Y5/00 , A61K38/45 , A61K47/665 , A61K47/6899 , A61K48/00 , C12N9/1077
摘要： Methods and compositions for killing replicating or non-replicating, targeted mammalian cells and bystander cells, comprising: (a) transfecting or transducing mammalian cells with a nucleic acid encoding a purine analog nucleoside cleavage enzyme, or providing the targeted cells directly with the enzyme; and (b) contacting the targeted cells with a purine analog nucleoside substrate for the enzyme to produce a toxic purine base analog thereby killing the targeted cells and bystander cells. In the present method of killing cells, the enzyme can be an E. coli purine analog nucleoside phosphorylase.

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