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1. 发明授权

US06780865B1 Compounds having selective hydrolytic potentials 失效
标题翻译：具有选择性水解电位的化合物
公开(公告)号：US06780865B1
公开(公告)日：2004-08-24
申请号：US08932834
申请日：1997-09-18
申请人： David Porubek , Anil M. Kumar , Charles R. Bredl , J. Peter Klein
发明人： David Porubek , Anil M. Kumar , Charles R. Bredl , J. Peter Klein
IPC分类号： C07D47310
CPC分类号： C07D473/04 , C07D473/10
摘要： Disclosed are compounds having selective hydrolytic potential. The disclosed compounds are useful as compounds having selective stability and are capable of undergoing programmed hydrolysis in biologic systems. The disclosed compounds have a structure of formula I:
摘要翻译：公开了具有选择性水解电位的化合物。所公开的化合物可用作具有选择性稳定性且能够在生物系统中进行程序水解的化合物。所公开的化合物具有式I的结构：

2. 发明授权

US07053096B2 Compounds having selective hydrolytic potentials 失效
公开(公告)号：US07053096B2
公开(公告)日：2006-05-30
申请号：US10838296
申请日：2004-05-05
申请人： David Porubek , Anil M. Kumar , Charles R. Bredl , J. Peter Klein
发明人： David Porubek , Anil M. Kumar , Charles R. Bredl , J. Peter Klein
IPC分类号： C07D473/10 , A61K31/522
CPC分类号： C07D473/04 , C07D473/10
摘要： Disclosed are compounds having selective hydrolytic potential. The disclosed compounds are useful as compounds having selective stability and are capable of undergoing programmed hydrolysis in biologic systems.

3. 发明授权

US06693105B1 Hydroxyl-containing compounds 失效
标题翻译：含羟基的化合物
公开(公告)号：US06693105B1
公开(公告)日：2004-02-17
申请号：US09361145
申请日：1999-07-27
申请人： Gail E. Underiner , David Porubek , J. Peter Klein , Paul Woodson , Stephen J. Klaus , Anil M. Kumar , John Tulinsky
发明人： Gail E. Underiner , David Porubek , J. Peter Klein , Paul Woodson , Stephen J. Klaus , Anil M. Kumar , John Tulinsky
IPC分类号： A61K31522
CPC分类号： C07D209/48 , A61K31/00 , A61K31/519 , A61K31/522 , C07C233/91 , C07C317/18 , C07D211/76 , C07D211/88 , C07D215/22 , C07D239/54 , C07D239/88 , C07D239/96 , C07D295/088 , C07D473/04 , C07D473/06 , C07D473/08 , C07D473/10 , C07D475/02 , C07D487/04 , C07D495/04 , C07D513/04 , Y10T436/147777
摘要： Disclosed are therapeutic compounds having the formula: (R)j—(CORE MOIETY), including resolved enantiomers, diastereomers, hydrates, salts, solvates or mixtures thereof where j is an integer from one to three. The core moiety is a bicyclic ring structure having at least one heterocyclic ring that contains five to six ring atoms and up to two nitrogen heteroatoms. R is selected from the group consisting of hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted benzyl, C1-6 alkyl or C1-6 alkenyl, and at least one R has the formula I: n is an integer from 1 to 20, at least one of X or Y is —OH. Another of X or Y, which is not —OH, is hydrogen, CH3—, CH3—CH2—, CH3—(CH2)2—or (CH3)2—CH2—, and each W1, W2, and W3 is independently hydrogen, CH3—, CH3—CH2—, CH3—(CH2)2— or (CH3)2—CH2—. The X, Y, W1, W2, or W3 alkyl groups may be unsubstituted or substituted by an hydroxyl, halo or dimethylamino group. The disclosed compounds and therapeutic compositions thereof are useful in treating individuals having a disease or treatment-induced toxicity, mediated by second messenger activity.
摘要翻译：公开了具有下式的治疗化合物：包括拆分的对映异构体，非对映异构体，水合物，盐，溶剂合物或其混合物，其中j是1至3的整数。核心部分是具有至少一个含有5至6个环原子和至多2个氮杂原子的杂环的双环结构。 R选自氢，卤素，羟基，氨基，取代或未取代的苄基，C 1-6烷基或C 1-6烯基，至少一个R具有式I：n为1至20的整数， X或Y中的至少一个是-OH。不是-OH的X或Y中的另一个是氢，CH 3 - ，CH 3 -CH 2 - ，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - ，并且每个W 1，W 2和W 3独立地是氢，CH 3 - ，CH 3 -CH 2 - ，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - 。 X，Y，W1，W2或W3烷基可以是未取代的或被羟基，卤素或二甲基氨基取代。所公开的化合物及其治疗组合物可用于治疗由第二信使活性介导的患有疾病或治疗诱导的毒性的个体。

4. 发明授权

US5521315A Olefin substituted long chain compounds 失效
标题翻译：烯烃取代的长链化合物
公开(公告)号：US5521315A
公开(公告)日：1996-05-28
申请号：US59697
申请日：1993-05-10
申请人： Gail Underiner , David Porubek , J. Peter Klein , Elisa Eiseman , Alistair Leigh , Anil Kumar , John Michnick
发明人： Gail Underiner , David Porubek , J. Peter Klein , Elisa Eiseman , Alistair Leigh , Anil Kumar , John Michnick
IPC分类号： C07D239/54 , A61K31/015 , A61K31/047 , A61K31/195 , A61K31/40 , A61K31/403 , A61K31/4035 , A61K31/505 , A61K31/52 , A61K31/522 , A61P1/00 , A61P1/02 , A61P1/16 , A61P3/00 , A61P3/08 , A61P3/10 , A61P11/00 , A61P13/02 , A61P15/00 , A61P19/10 , A61P25/28 , A61P29/00 , A61P37/00 , A61P43/00 , C07C13/08 , C07C13/16 , C07C15/40 , C07C49/20 , C07C49/647 , C07D209/48 , C07D473/06 , C07D211/88 , C07D239/80
CPC分类号： C07D473/06
摘要： There is disclosed an olefin-substituted compound having the formula:R--(core moiety),wherein R is a straignt chain hydrocarbon having at least one double bond and a carbon chain length of from about 6 to about 18 carbon atoms, wherein multiple double bonds are separated from each other by at least three carbon atoms, wherein the closest double bond to the core moiety is at least five carbon atoms from the core moiety, and wherein the hydrocarbon chain may be substituted by a hydroxyl, halo, keto or dimethylanimo group and/or interrupted by an oxygen atom and salts thereof and pharmaceutical compositions thereof.
摘要翻译：公开了具有下式的烯烃取代的化合物：R-（核心部分），其中R是具有至少一个双键且碳链长度为约6至约18个碳原子的直链烃，其中多个双键彼此分开至少三个碳原子，其中与核心部分最接近的双键是至少五个来自核心部分的碳原子，并且其中烃链可以被羟基，卤素，酮基或二甲基亚胺基取代组和/或被氧原子及其盐和其药物组合物中断。

5. 发明授权

US5780476A Hydroxyl-containing xanthine compounds 失效
标题翻译：含羟基黄嘌呤化合物
公开(公告)号：US5780476A
公开(公告)日：1998-07-14
申请号：US468660
申请日：1995-06-06
申请人： Gail E. Underiner , David Porubek , J. Peter Klein , Paul Woodson
发明人： Gail E. Underiner , David Porubek , J. Peter Klein , Paul Woodson
IPC分类号： A61K31/519 , A61K31/522 , A61K31/52 , C07D473/04
CPC分类号： A61K31/522 , A61K31/519
摘要： Disclosed are therapeutic compounds having the formula: (R)j - (core moiety), including resolved enantiomers, diastereomers, hydrates, salts, solvates and mixtures thereof. j is an integer from one to three, the core moiety is either non-cyclic or comprises at least one five- to seven-membered ring structure, R may be selected from the group consisting of hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted benzyl, C.sub.1-6 alkyl or C.sub.1-6 alkenyl, and at least one R has the formula I: ##STR1## n is an integer from seven to twenty and at least one of X or Y is --OH. The other of X or Y, which is not --OH, is hydrogen, CH.sub.3 --, CH.sub.3 --CH.sub.2 --, CH.sub.3 --(CH.sub.2).sub.2 -- or (CH.sub.3).sub.2 --CH.sub.2 --, and each W.sub.1, W.sub.2, and W.sub.3 is independently hydrogen, CH.sub.3 --, CH.sub.3 --CH.sub.2 --, CH.sub.3 --(CH.sub.2).sub.2 -- or (CH.sub.3).sub.2 --CH.sub.2 --. The X, Y, W.sub.1, W.sub.2, or W.sub.3 alkyl groups may be unsubstituted or substituted by an hydroxyl, halo or dimethylamino group. The disclosed compounds and therapeutic compositions thereof are useful in treating individuals having a disease or treatment-induced toxicity, mediated by second messenger activity.
摘要翻译：公开了具有下式的治疗化合物：（R）j-（核心部分），包括拆分的对映异构体，非对映体，水合物，盐，溶剂合物及其混合物。 j是1至3的整数，核心部分是非环状的或包含至少一个五至七元环结构，R可以选自氢，卤素，羟基，氨基，取代或未取代的苄基，C 1-6烷基或C 1-6烯基，并且至少一个R具有式I：I是7至20的整数，X或Y中的至少一个是-OH。不是-OH的X或Y中的另一个是氢，CH 3 - ，CH 3 -CH 2 - ，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - ，并且每个W 1，W 2和W 3独立地氢，CH 3 - ，CH 3 -CH 2 - ，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - 。 X，Y，W1，W2或W3烷基可以是未取代的或被羟基，卤素或二甲基氨基取代。所公开的化合物及其治疗组合物可用于治疗由第二信使活性介导的患有疾病或治疗诱导的毒性的个体。

6. 发明授权

US6133274A Hydroxyl-containing bicyclic compounds 失效
标题翻译：含羟基的双环化合物
公开(公告)号：US6133274A
公开(公告)日：2000-10-17
申请号：US756703
申请日：1996-11-26
申请人： Gail E. Underiner , David Porubek , J. Peter Klein , Paul Woodson
发明人： Gail E. Underiner , David Porubek , J. Peter Klein , Paul Woodson
IPC分类号： A61K31/519 , A61K31/522 , C07D473/04 , A61K31/52
CPC分类号： A61K31/522 , A61K31/519
摘要： Disclosed are therapeutic compounds having the formula:(R)j-(core moiety),including resolved enantiomers, diastereomers, hydrates, salts, solvates and mixtures thereof. j is an integer from one to three, the core moiety is either non-cyclic or comprises at least one five- to seven-membered ring structure, R may be selected from the group consisting of hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted benzyl, C.sub.1-6 alkyl or C.sub.1-6 alkenyl, and at least one R has the formula I: ##STR1## n is an integer from seven to twenty and at least one of X or Y is --OH. The other of X or Y, which is not --OH, is hydrogen, CH.sub.3 --, CH.sub.3 --CH.sub.2 --, CH.sub.3 --(CH.sub.2).sub.2 -- or (CH.sub.3).sub.2 --CH.sub.2 --, and each W.sub.1, W.sub.2, and W.sub.3 is independently hydrogen, CH.sub.3 --, CH.sub.3 --CH.sub.2 --, CH.sub.3 --(CH.sub.2).sub.2 -- or (CH.sub.3).sub.2 --CH.sub.2 --. The X, Y, W.sub.1, W.sub.2, or W.sub.3 alkyl groups may be unsubstituted or substituted by an hydroxyl, halo or dimethylamino group. The disclosed compounds and therapeutic compositions thereof are useful in treating individuals having a disease or treatment-induced toxicity, mediated by second messenger activity.
摘要翻译：公开了具有下式的治疗化合物：（R）j-（核心部分），包括拆分的对映异构体，非对映体，水合物，盐，溶剂合物及其混合物。 j是1至3的整数，核心部分是非环状的或包含至少一个五至七元环结构，R可以选自氢，卤素，羟基，氨基，取代或未取代的苄基，C 1-6烷基或C 1-6烯基，并且至少一个R具有式I：n是7至20的整数，X或Y中的至少一个是-OH。不是-OH的X或Y中的另一个是氢，CH 3 - ，CH 3 -CH 2 - ，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - ，并且每个W 1，W 2和W 3独立地氢，CH 3 - ，CH 3 -CH 2 - ，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - 。 X，Y，W1，W2或W3烷基可以是未取代的或被羟基，卤素或二甲基氨基取代。所公开的化合物及其治疗组合物可用于治疗由第二信使活性介导的患有疾病或治疗诱导的毒性的个体。

7. 发明授权

US5473070A Substituted long chain alcohol xanthine compounds 失效
标题翻译：取代长链醇黄嘌呤化合物
公开(公告)号：US5473070A
公开(公告)日：1995-12-05
申请号：US976353
申请日：1992-11-16
申请人： Gail Underiner , David Porubek , J. Peter Klein , Paul Woodson
发明人： Gail Underiner , David Porubek , J. Peter Klein , Paul Woodson
IPC分类号： A61K31/519 , C07C233/91 , C07C317/18 , C07D209/48 , C07D211/76 , C07D211/88 , C07D215/22 , C07D239/54 , C07D239/88 , C07D239/96 , C07D295/088 , C07D473/06 , C07D473/08 , C07D473/10 , C07D475/02 , C07D473/04 , A61K31/52
CPC分类号： C07D209/48 , A61K31/519 , C07C233/91 , C07C317/18 , C07D211/76 , C07D211/88 , C07D215/22 , C07D239/54 , C07D239/88 , C07D239/96 , C07D295/088 , C07D473/06 , C07D473/08 , C07D473/10 , C07D475/02
摘要： There is disclosed compounds and pharmaceutical compositions comprising compounds of the formula: ##STR1## wherein each of one or two R is independently ##STR2## wherein n is an integer from 7 to 20, at least one of X or Y is --OH and if one of X or Y is --OH then the other X or Y is H, CH.sub.3, CH.sub.3 --CH.sub.2, CH.sub.3 --(CH.sub.2).sub.2 --, or (CH.sub.3).sub.2 --CH.sub.2 --, and W.sub.1, W.sub.2, and W.sub.3 is independently H, CH.sub.3, CH.sub.3 --CH.sub.2, CH.sub.3 --(CH.sub.2).sub.2 --, or (CH.sub.3).sub.2 --CH.sub.2 --, and wherein the alkyl groups may be substituted by a hydroxyl, halo or dimethylamino group and/or interrupted by an oxygen atom, H or alkyl (1-4C), including resolved enantiomers and/or diastereomers, salts and mixtures thereof. In particular, the compounds lower elevated levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) derived from said PA within seconds of the primary stimulus and their contact with said cells. The modulatory effect depends on the nature of the target cell and the stimulus applied.
摘要翻译：公开了包含下式化合物的化合物和药物组合物：独立地为：其中n为7至20的整数，X或Y中的至少一个为-OH，如果X或Y中的一个为-OH，则其它X或Y是H，CH 3，CH 3 -CH 2，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - ，W 1，W 2和W 3独立地为H，CH 3，CH 3 -CH 2， CH 2）2 - 或（CH 3）2 -CH 2 - ，并且其中烷基可以被羟基，卤素或二甲基氨基取代和/或被氧原子H或烷基（1-4C）中断，包括拆分的对映异构体和/或非对映体，其盐和混合物。特别地，所述化合物在主刺激的几秒钟内与所述细胞的接触降低了源自所述PA的不饱和，非花生四烯酸磷脂酸（PA）和二酰基甘油（DAG）的升高水平。调节作用取决于靶细胞的性质和应用的刺激。

8. 发明授权

US5354756A Olefin-substituted long chain xanthine compounds 失效
标题翻译：烯烃取代的长链黄嘌呤化合物
公开(公告)号：US5354756A
公开(公告)日：1994-10-11
申请号：US3372
申请日：1993-01-12
申请人： Gail Underiner , David Porubek , J. Peter Klein
发明人： Gail Underiner , David Porubek , J. Peter Klein
IPC分类号： C07D473/06 , A61K31/52 , C07D473/02
CPC分类号： C07D473/06
摘要： There is disclosed compounds and pharmaceutical compositions having a xanthine core and one or two hydrocarbon side chains bonded to a ring nitrogen atom, wherein the hydrocarbon side chains are independently a straight chain hydrocarbon having at least one double bond in a carbon chain length of from about 4 to about 18 carbon atoms in length, wherein multiple double bonds are separated from each other by at least three carbon atoms, and wherein the hydrocarbon chain may be substituted by a hydroxyl, halo or dimethylamino group and/or interrupted by an oxygen atom. The compounds lower elevated levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) derived from said PA within seconds of the primary stimulus and their contact with cells. The modulatory effect depends on the nature of the target cell and the stimulus applied.
摘要翻译：公开了具有与环氮原子键合的黄嘌呤核和一个或两个烃侧链的化合物和药物组合物，其中烃侧链独立地为具有至少一个双键的碳链长度为约 4至约18个碳原子，其中多个双键彼此分开至少三个碳原子，并且其中烃链可以被羟基，卤素或二甲基氨基取代和/或被氧原子中断。该化合物在主要刺激的几秒钟内和与细胞接触的情况下，降低了源自所述PA的不饱和，非花生四烯酸磷脂酸（PA）和二酰基甘油（DAG）的升高水平。调节作用取决于靶细胞的性质和应用的刺激。

9. 发明授权

US5804584A Therapeutic compounds containing a monocyclic five- to six- membered ring structure having one to two nitrogen atoms 失效
标题翻译：含有1至2个氮原子的单环五至六元环结构的治疗化合物
公开(公告)号：US5804584A
公开(公告)日：1998-09-08
申请号：US468659
申请日：1995-06-06
申请人： Gail E. Underiner , David Porubek , J. Peter Klein , Paul Woodson
发明人： Gail E. Underiner , David Porubek , J. Peter Klein , Paul Woodson
IPC分类号： A61K31/519 , A61K31/522 , C07D239/54 , A61K31/52
CPC分类号： A61K31/522 , A61K31/519
摘要： Disclosed are therapeutic compounds having the formula: (R)j-(core moiety), including resolved enantiomers, diastereomers, hydrates, salts, solvates and mixtures thereof. j is an integer from one to three, the core moiety is either non-cyclic or comprises at least one five- to seven-membered ring structure, R may be selected from the group consisting of hydrogen, halogen, hydroxyl, amino, substituted or unsubstituted benzyl, C.sub.1-6 alkyl or C.sub.1-6 alkenyl, and at least one R has the formula I: ##STR1## n is an integer from seven to twenty and at least one of X or Y is --OH. The other of X or Y, which is not --OH, is hydrogen, CH.sub.3 --, CH.sub.3 --CH.sub.2 --, CH.sub.3 --(CH.sub.2).sub.2 -- or (CH.sub.3).sub.2 --CH.sub.2 --, and each W.sub.1, W.sub.2, and W.sub.3 is independently hydrogen, CH.sub.3 --, CH.sub.3 --CH.sub.2 --, CH.sub.3 --(CH.sub.2).sub.2 -- or (CH.sub.3).sub.2 --CH.sub.2 --. The X, Y, W.sub.1, W.sub.2, or W.sub.3 alkyl groups may be unsubstituted or substituted by an hydroxyl, halo or dimethylamino group. The disclosed compounds and therapeutic compositions thereof are useful in treating individuals having a disease or treatment-induced toxicity, mediated by second messenger activity.
摘要翻译：公开了具有下式的治疗化合物：（R）j-（核心部分），包括拆分的对映异构体，非对映体，水合物，盐，溶剂合物及其混合物。 j是1至3的整数，核心部分是非环状的或包含至少一个五至七元环结构，R可以选自氢，卤素，羟基，氨基，取代或未取代的苄基，C 1-6烷基或C 1-6烯基，并且至少一个R具有式I：I是7至20的整数，X或Y中的至少一个是-OH。不是-OH的X或Y中的另一个是氢，CH 3 - ，CH 3 -CH 2 - ，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - ，并且每个W 1，W 2和W 3独立地氢，CH 3 - ，CH 3 -CH 2 - ，CH 3 - （CH 2）2 - 或（CH 3）2 -CH 2 - 。 X，Y，W1，W2或W3烷基可以是未取代的或被羟基，卤素或二甲基氨基取代。所公开的化合物及其治疗组合物可用于治疗由第二信使活性介导的患有疾病或治疗诱导的毒性的个体。

10. 发明授权

US5288721A Substituted epoxyalkyl xanthines 失效
标题翻译：取代的环氧烷基黄嘌呤
公开(公告)号：US5288721A
公开(公告)日：1994-02-22
申请号：US949330
申请日：1992-09-22
申请人： J. Peter Klein , David Porubek , Glenn C. Rice , Paul Woodson
发明人： J. Peter Klein , David Porubek , Glenn C. Rice , Paul Woodson
IPC分类号： C07D473/08 , C07D473/10 , A61K31/52 , C07D473/04
CPC分类号： C07D473/08 , C07D473/10
摘要： Compounds of the formula ##STR1## including the resolved enantiomers and/or diastereomers and mixtures thereof wherein each of one or two R is independently ##STR2## wherein n is 1-16 and R' is H or alkyl(1-4C); and wherein each remaining R is independently H, alkyl(1-6C), alkenyl(1-6C) or benzyl; an wherein said alkyl or alkenyl may be substituted by a hydroxyl, halo, or dimethylamino group, and/or interrupted by an oxygen atom, are useful in modulating the effects of internal and external stimuli on cells by reversing the effects of these stimuli on the short-term secondary messenger pathways. In particular, the compounds lower elevated levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) derived from said PA within seconds of the primary stimulus and their contact with said cells. The modulatory effect depends on the nature of the target cell and the stimulus applied.
摘要翻译：式（1）的化合物包括拆分的对映体和/或非对映异构体及其混合物，其中一个或两个R R中的每一个独立地为（2），其中n为1-16且R'为H或烷基（ 1-4C）; 并且其中每个剩余的R独立地为H，烷基（1-6C），烯基（1-6C）或苄基; 其中所述烷基或烯基可以被羟基，卤素或二甲基氨基取代和/或被氧原子间隔，可用于通过将这些刺激的作用逆转到细胞上来调节内部和外部刺激对细胞的影响短期二级信使途径。特别地，所述化合物在主刺激的几秒钟内与所述细胞的接触降低了源自所述PA的不饱和，非花生四烯酸磷脂酸（PA）和二酰基甘油（DAG）的升高水平。调节作用取决于靶细胞的性质和应用的刺激。

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