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1. 发明公开

EP2892515A1 BENZOQUINONE DERIVATIVES FOR TREATING OXIDATIVE STRESS DISORDERS 审中-公开
标题翻译： BENZOCHINONDERIVATE ZUR BEHANDLUNG VON氧化应变片
公开(公告)号：EP2892515A1
公开(公告)日：2015-07-15
申请号：EP13762705.5
申请日：2013-09-06
申请人： Edison Pharmaceuticals, Inc.
发明人： SHRADER, William, D. , HINMAN, Andrew, W. , KHEIFETS, Viktoria
IPC分类号： A61K31/045 , A61K31/16 , A61K31/19 , A61K31/277 , C07C33/02 , C07C33/04 , C07C255/01 , C07C53/126 , C07C233/11 , A61P39/06
CPC分类号： A61K31/122 , A61K31/05 , A61K31/198 , C07C66/00
摘要： Disclosed herein are compounds and methods of using such compounds for treating or suppressing oxidative stress disorders, including mitochondrial disorders, impaired energy processing disorders, neurodegenerative diseases and diseases of aging, or for modulating one or more energy biomarkers, normalizing one or more energy biomarkers, or enhancing one or more energy biomarkers, wherein the compound is a compound of Formula I or Formula II: wherein: R1 and R2 are independently hydrogen, (C1-C6)alkyl or —O(C1-C6)alkyl; or R1 and R2 together represent —CH═CH—CH═CH—; R3 is (C1-C6)alkyl; X is —CH═CH— or —C≡C—; m is 1-10; n is 1-5; k is 1-3, with the proviso that when k is an integer of 2 or 3, n is independently 1-5 in each occurrence of the —X—(CH2)n— group; Y is —OR4, —CN, —C(=0)OR5, —C(=0)R5, or —C(=0)N(R6)2; R4 and R5 are independently selected from the group consisting of hydrogen, —(C1-C6)alkyl, —(C1-C6)haloalkyl, —C(=0)-(C1-C6)alkyl, —C(=0)-(C1-C6)haloalkyl, —C(=0)-NH(C1-C6)alkyl, —C(=0)-N((C1-C6)alkyl)2, —C(=0)-NH2, and phenyl, wherein the phenyl group may optionally be substituted with a substituent selected from the group consisting of —(C1-C6)alkyl, -0-(C1-C6)alkyl, —(C1-C6)haloalkyl, and halo; each R6 is independently hydrogen or —(C1-C6)alkyl; and M is —H, —C(0)—R7 or —C(0)0-R7, wherein R7 is —(C1-C6)alkyl or phenyl; or a stereoisomer, mixture of stereoisomers, pharmaceutically acceptable salt, crystalline form, non-crystalline form, hydrate or solvate thereof.
摘要翻译：本文公开了使用这些化合物治疗或抑制氧化应激障碍（包括线粒体病症，受损能量加工障碍，神经退行性疾病和衰老疾病）或用于调节一种或多种能量生物标志物，使一种或多种能量生物标志物正常化的化合物和方法，或增强一种或多种能量生物标志物，其中所述化合物是式I或式II的化合物：其中：R 1和R 2独立地是氢，（C 1 -C 6）烷基或-O（C 1 -C 6）烷基; 或者R1和R2一起表示-CH = CH-CH = CH-; R3是（C1-C6）烷基; X是-CH = CH-或-C≡C-; m为1-10; n为1-5; k为1-3，条件是当k为2或3的整数时，每个出现的-X-（CH 2）n - 基团，n独立地为1-5。 Y是-OR 4，-CN，-C（= O）OR 5，-C（= O）R 5或-C（= O）N（R 6）2; R4和R5独立地选自氢， - （C1-C6）烷基， - （C1-C6）卤代烷基，-C（= O） - （C1-C6）烷基，-C（= O）（C 1 -C 6）烷基，-C（= O）-NH（C 1 -C 6）烷基，-C（= O）-N（（C 1 -C 6）烷基）2，-C（= O）-NH 2，苯基，其中苯基可以任选被选自 - （C 1 -C 6）烷基，-O-（C 1 -C 6）烷基， - （C 1 -C 6）卤代烷基和卤素的取代基取代; 每个R 6独立地是氢或 - （C 1 -C 6）烷基; 并且M是-H，-C（O）-R 7或-C（O）O-R 7，其中R 7是 - （C 1 -C 6）烷基或苯基; 或立体异构体，立体异构体的混合物，药学上可接受的盐，结晶形式，非结晶形式，水合物或溶剂化物。

2. 发明授权

EP0748219B1 COMPOUNDS FOR THE TREATMENT OF DISORDERS RELATED TO VASCULOGENESIS AND/OR ANGIOGENESIS 失效
标题翻译：化合物与血管生成和/或血管相关疾病的治疗。
公开(公告)号：EP0748219B1
公开(公告)日：2005-04-06
申请号：EP95910239.3
申请日：1995-02-09
申请人： Sugen, Inc. , YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM
发明人： GAZIT, Aviv , LEVITZKI, Alexander , APP, Harald , TANG, Cho, Peng , MCMAHON, Gerald, M.
IPC分类号： A61K31/24 , A61K31/42 , A61K31/275 , A61K31/415 , A61K31/495 , C07C211/45 , C07C255/01 , C07D209/18 , C07D231/38 , C07D241/36 , C07C255/41 , C07D239/93
CPC分类号： C07D487/04 , A61K31/235 , A61K31/275 , A61K31/277 , A61K31/38 , A61K31/40 , A61K31/415 , A61K31/42 , A61K31/495 , A61K31/502 , A61K31/505 , A61K31/517 , A61K31/535 , A61K38/00 , C07C229/60 , C07C255/36 , C07C255/40 , C07C255/41 , C07C255/66 , C07C317/46 , C07C327/44 , C07D209/18 , C07D239/93 , C07D239/94 , C07D241/42 , C07D241/44 , C07K14/71 , C07K16/2863 , C07K2319/32 , G01N33/5008 , G01N33/5011 , G01N33/502 , G01N33/5064 , G01N33/5091 , G01N33/6893 , G01N2333/71 , G01N2500/04
摘要： The present invention relates to organic molecules capable of modulating tyrosine kinase signal transduction and particularly KDR/FLK-1 receptor signal transduction in order to regulate and/or modulate vasculogenesis and angiogenesis. The invention is based, in part, on the demonstration that KDR/FLK-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of FLK-1. These results indicate a major role for KDR/FLK-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express FLK-1 and the uses of expressed FLK-1 to evaluate and screen for drugs and analogs of VEGF involved in FLK-1 modulation by either agonist or antagonist activities is also described. The invention also relates to the use of the disclosed compounds in the treatment of disorders, including cancer, diabetes, hemangioma and Kaposi's sarcoma, which are related to vasculogenesis and angiogenesis.

3. 发明公开

EP0455826A4 SUBSTITUTED OPEN-CHAIN TERPENE COMPOUND 失效
标题翻译：取代的开链化合物
公开(公告)号：EP0455826A4
公开(公告)日：1993-10-06
申请号：EP90917539
申请日：1990-11-29
申请人： MITSUBISHI KASEI CORPORATION
发明人： TAKAYANAGI, HISAO , KITANO, YASUNORI , MORINAKA, YASUHIRO
IPC分类号： C07C33/02 , C07C43/178 , C07C43/315 , C07C45/44 , C07C45/51 , C07C45/63 , C07C45/67 , C07C47/21 , C07C47/24 , C07C47/263 , C07C47/277 , C07C49/203 , C07C49/227 , C07C49/24 , C07C49/255 , C07C49/587 , C07C69/007 , C07C69/738 , C07C255/07 , C07C255/10 , C07C255/15 , C07C255/46 , C07C309/65 , C07D309/06 , C07D309/12 , C07F7/18 , C07C33/048 , C07C43/02 , C07C47/20 , C07C69/78 , C07C255/01 , C07C309/66 , C07C309/73
CPC分类号： C07F7/1856 , C07C33/02 , C07C43/178 , C07C43/315 , C07C45/44 , C07C45/512 , C07C45/516 , C07C45/63 , C07C45/673 , C07C45/676 , C07C47/21 , C07C47/24 , C07C47/263 , C07C47/277 , C07C49/203 , C07C49/227 , C07C49/24 , C07C49/255 , C07C49/587 , C07C69/007 , C07C69/738 , C07C255/07 , C07C255/10 , C07C255/15 , C07C255/46 , C07C309/65 , C07C2601/18 , C07D309/06 , C07D309/12 , C07F7/1852
摘要： A novel substituted open-chain terpene compound of general formula (I) which is useful as an intermediate for the synthesis of sarcophytol A, wherein R is (α), (β), or (γ) (wherein R1 is cyano or formyl R2 is hydrogen or CO¿2?R?3, R3 is C¿1 to C4 alkyl, and R4 is -C=CH or -CH=CH¿2?); X is hydrogen, hydroxyl, halogen, OR?5¿ or OSO¿2R?6 (wherein R5 is hydrogen, 1-alkoxyalkyl, tetrahydrofuryl, tetrahydropyranyl, acyl, or silyl substituted by C¿1? to C5 alkyl or phenyl, and R?6 is C¿1 to C4 alkyl which may be substituted by halogen or phenyl which may be substituted by C1 to C4 alkyl); and n is an integer of 0 to 2, provided that X is OR5 and n is O when R is (β) or (γ); X is neither halogen nor OSO¿2?R?6 when R1¿ is formyl; R2 is not hydrogen when R5 is hydrogen; and R3 is not methyl when R5 is 1-ethoxyethyl.
摘要翻译： Substd。式（I）的萜烯是新的。在（I）中R = CH = CHCHR1CH（CH3）2（gp.a），CH2CHR2COR3（gp.B）或CH2CH2C（OH）（R4）CH3（gp.c）; R1 = CN或CHO; R2 = H或CO2R3; R3 = 1-4C烷基; R4 = C = CH或CH = CH2; X = H，OH，卤素，OR 5或OSO 2 R 6; R5 = H，1-烷氧基烷基，四氢呋喃基，四氢吡喃基，酰基或甲硅烷基。 1-5C烷基或苯基; R6 = 1-4C烷基选择。 substd。通过卤素或苯基取代。 substd。通过1-4C烷基; n = 0-2; 条件是（i）当R = gp时。（b）或（c）X = OR5和n = O; （ii）当R1 = CHO时，X不为卤素或OSO2R6; （iii）当R5 = H时，R2不为H; （iv）当R5 = 1-乙氧基乙基时，则R3不是Me。

6. 发明授权

EP0240121B1 Diphenyl ether derivatives 失效
标题翻译：二苯醚衍生物
公开(公告)号：EP0240121B1
公开(公告)日：1991-04-17
申请号：EP87301386.6
申请日：1987-02-18
申请人： IMPERIAL CHEMICAL INDUSTRIES PLC
发明人： Bushell, Michael John , Carr, Robin Arthur Ellis
IPC分类号： C07C43/257 , C07C43/225 , C07C255/01 , C07D213/64 , C07D317/50 , C07F9/40 , C07F9/54 , A01N31/14 , A01N37/34 , A01N43/30 , A01N43/40
CPC分类号： C07D213/643 , A01N31/14 , A01N43/30 , A01N43/40 , A01N47/02 , A01N49/00 , C07C43/225 , C07C43/29 , C07C43/295 , C07D213/46 , C07D317/46

8. 发明授权

EP0290570B1 CHIRALE ODER ACHIRALE RINGVERBINDUNGEN 失效
公开(公告)号：EP0290570B1
公开(公告)日：1992-09-23
申请号：EP87907946.5
申请日：1987-10-30
申请人： MERCK PATENT GmbH
发明人： WÄCHTLER, Andreas , KRAUSE, Joachim , PAULUTH, Detlef , GEELHAAR, Thomas
IPC分类号： C07D239/26 , C07D213/30 , C07C255/01 , C09K19/12 , C09K19/34
CPC分类号： C07D239/26 , C07C255/00 , C09K19/126 , C09K19/3444 , C09K19/3463
摘要： Chiral or achiral cyclic compounds of formula (I): R1-(A1-Z1)m-A2-Q1-C*R°X-Q2-(A3-Z2)n-(A4)o-R2, in which R1 and R2, independently of one another, represent an alkyl or perfluoralkyl group with 1 to 12 C atoms, in which also one or two non-adjacent CH2 or CF2 groups can be replaced by O atoms and/or -CO- groups and/or -CO-O- groups and/or -CH=CH- groups and/or -CHhalogen- and/or -CHCN- groups and/or -O-CO-CHhalogen- and/or -CO-O-CHCN- groups; one of the groups R1 and R2 also represents H, F, Cl, Br or CN, R1 is also -Q1-C*R°X-Q2-R2, whereby Q1, R°, X, Q2 and R2 have the same notations; A1, A2, A3 and A4, independently of each other, represent an unsubstituted 1,4 phenylene or substituted by one or two F and/or Cl atoms and/or CH3 groups and/or CN groups, wherein also one or two CH groups can be replaced by N; 1,4-cyclohexylene, wherein also one or two non-adjacent CH2 groups can be replaced by O atoms and/or S atoms; piperidine-1,4-diyl, 1,4-bicyclo(2,2,2)octylene-, 1,3,4-thiadiazol-2,5-diyl, naphthalene-2,6-diyl-, decahydronaphthalene-2,6-diyl- or 1,2,3,4-tetrahydronaphthalene-2,6-diyl-; Z1 and Z2 are individually -CO-O-, -O-CO-, -CH2CH2-, -OCH2-, -CH2O-, -C=C- or a simple bond; X is halogen, CN or CH3, R° is an alkyl group different from X (and where n= o= 0 also from R2); C* is a carbon atom combined with four different substituents; m and n each, independently of one another, are 0, 1, 2 or 3; o is 0 or 1; (m + n + o) is 1, 2, 3 or 4; and Q1 and Q2, each independently of one another, are alkylene with 1 to 4 C atoms, where also a CH2 group can be replaced by -O-, -S-, -CO-, -O-CO-, -CO-O-, -S-CO-, -CO-S-, -CH=CH-COO-, -CH=CH-, -CHhalogen- and/or -CHCN-, or a simple bond. These compounds can be used as constituents of chirally tilted smectic liquid crystal phases.
摘要翻译：式（I）的手性或非手性环状化合物：其中R 1和R 2独立地选自氢，C 1 -C 4烷基，C 1 -C 4烷基，C 1 -C 4烷基， R 2彼此独立地表示具有1至12个C原子的烷基或全氟烷基，其中一个或两个不相邻的CH 2或CF 2基团也可以被O原子和/或-CO-基团和/或 - CO-O-基团和/或-CH = CH-基团和/或-CH-卤素 - 和/或-CHCN-基团和/或-O-CO-卤代 - 和/或-CO-O-CHCN-基团; 基团R1和R2中的一个还表示H，F，Cl，Br或CN，R1也是-Q1-C * R°X-Q2-R2，其中Q1，R°，X，Q2和R2具有相同的符号 ; A1，A2，A3和A4彼此独立地表示未取代的1,4亚苯基或被一个或两个F和/或Cl原子和/或CH3基团和/或CN基团取代，其中还有一个或两个CH基团可以用N代替; 其中还有一个或两个不相邻的CH 2基团可以被O原子和/或S原子代替; 哌啶-1,4-二基，1,4-双环（2,2,2）亚辛基-1,3,4-噻二唑-2,5-二基，萘-2,6-二基，十氢萘-2， 6-二基 - 或1,2,3,4-四氢萘-2,6-二基; Z 1和Z 2分别为-CO-O - ， - O-CO-，-CH 2 CH 2 - ， - OCH 2 - ， - CH 2 O-，-C≡C-或单键; X为卤素，CN或CH 3，R 0为不同于X的烷基（并且其中n = 0 = 0也来自R 2）; C *是与四个不同取代基结合的碳原子; m和n各自彼此独立地为0,1,2或3; o是0或1; （m + n + o）是1,2,3或4; 并且Q1和Q2各自彼此独立地为具有1至4个C原子的亚烷基，其中CH2基团也可以被-O - ， - S - ， - CO - ， - O-CO - ， - CO- ，-S-CO-，-CO-S-，-CH = CH-COO - ， - CH = CH-，-CH-卤素 - 和/或-CHCN-，或简单的键。这些化合物可以用作手性倾斜近晶型液晶相的组分。

9. 发明授权

EP0306547B1 2-Hydrocarbyl-3,6-dichloropyridines and their preparation 失效转让
标题翻译： 2-油酰基-3,6-二氯吡啶及其制备方法
公开(公告)号：EP0306547B1
公开(公告)日：1992-06-10
申请号：EP87113211.4
申请日：1987-09-09
申请人： DOWELANCO
发明人： Halpern, Marc E. , Dietsche, Thomas J. , Orvik, Jon A. , Barron, Brian J.
IPC分类号： C07C255/01 , C07D213/61 , C07C253/30
CPC分类号： C07C255/00 , C07D213/61

10. 发明公开

EP0455826A1 SUBSTITUTED OPEN-CHAIN TERPENE COMPOUND 失效
标题翻译： SUBSTITUIERTE OFFENKETTIGE TERPENVERBINDUNGEN。
公开(公告)号：EP0455826A1
公开(公告)日：1991-11-13
申请号：EP90917539.0
申请日：1990-11-29
申请人： Mitsubishi Chemical Corporation
发明人： TAKAYANAGI, Hisao , KITANO, Yasunori , MORINAKA, Yasuhiro
IPC分类号： C07C33/02 , C07C33/048 , C07C43/02 , C07C47/20 , C07C49/255 , C07C69/738 , C07C69/78 , C07C255/01 , C07C309/66 , C07C309/73 , C07F7/18
CPC分类号： C07F7/1856 , C07C33/02 , C07C43/178 , C07C43/315 , C07C45/44 , C07C45/512 , C07C45/516 , C07C45/63 , C07C45/673 , C07C45/676 , C07C47/21 , C07C47/24 , C07C47/263 , C07C47/277 , C07C49/203 , C07C49/227 , C07C49/24 , C07C49/255 , C07C49/587 , C07C69/007 , C07C69/738 , C07C255/07 , C07C255/10 , C07C255/15 , C07C255/46 , C07C309/65 , C07C2601/18 , C07D309/06 , C07D309/12 , C07F7/1852
摘要： A novel substituted open-chain terpene compound of general formula (I) which is useful as an intermediate for the synthesis of sarcophytol A, wherein R is (α), (β), or (ψ) (wherein R¹ is cyano or formyl R² is hydrogen or CO₂R³, R³ is C₁ to C₄ alkyl, and R⁴ is -C=CH or -CH=CH₂); X is hydrogen, hydroxyl, halogen, OR⁵ or OSO₂R⁶ (wherein R⁵ is hydrogen, 1-alkoxyalkyl, tetrahydrofuryl, tetrahydropyranyl, acyl, or silyl substituted by C₁ to C₅ alkyl or phenyl, and R⁶ is C₁ to C₄ alkyl which may be substituted by halogen or phenyl which may be substituted by C₁ to C₄ alkyl); and n is an integer of O to 2, provided that X is OR⁵ and n is O when R is (β) or (ψ); X is neither halogen nor OSO₂R⁶ when R¹ is formyl; R² is not hydrogen when R⁵ is hydrogen; and R³ is not methyl when R⁵ is 1-ethoxyethyl.
摘要翻译： Substd。式（I）的萜烯是新的。在（I）中R = CH = CHCHR1CH（CH3）2（gp.a），CH2CHR2COR3（gp.B）或CH2CH2C（OH）（R4）CH3（gp.c）; R1 = CN或CHO; R2 = H或CO2R3; R3 = 1-4C烷基; R4 = C = CH或CH = CH2; X = H，OH，卤素，OR 5或OSO 2 R 6; R5 = H，1-烷氧基烷基，四氢呋喃基，四氢吡喃基，酰基或甲硅烷基。 1-5C烷基或苯基; R6 = 1-4C烷基选择。 substd。通过卤素或苯基取代。 substd。通过1-4C烷基; n = 0-2; 条件是（i）当R = gp时。（b）或（c）X = OR5和n = O; （ii）当R1 = CHO时，X不为卤素或OSO2R6; （iii）当R5 = H时，R2不为H; （iv）当R5 = 1-乙氧基乙基时，则R3不是Me。

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