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1. 发明申请

US20080146580A1 Anititumoral Ecteinascidin Derivatives 有权
标题翻译：胰岛素抗坏血酸衍生物
公开(公告)号：US20080146580A1
公开(公告)日：2008-06-19
申请号：US11733606
申请日：2007-04-10
申请人： Maria Flores , Andres Francesh , Pilar Gallego , Jose Luis Chicharro , Maria Zarzuelo , Carolina Fernandez , Ignacio Manzanares
发明人： Maria Flores , Andres Francesh , Pilar Gallego , Jose Luis Chicharro , Maria Zarzuelo , Carolina Fernandez , Ignacio Manzanares
IPC分类号： A61K31/4995 , C07D267/22 , A61P35/00
CPC分类号： C07D515/22
摘要： This invention relates to antitumoral ecteinascidin derivatives.
摘要翻译：本发明涉及抗肿瘤抗坏血酸衍生物。

2. 发明授权

US07919493B2 Anititumoral ecteinascidin derivatives 有权
标题翻译：抗肿瘤抗坏血酸衍生物
公开(公告)号：US07919493B2
公开(公告)日：2011-04-05
申请号：US11733606
申请日：2007-04-10
申请人： Maria Flores , Andres Francesh , Pilar Gallego , Jose Luis Chicharro , Maria Zarzuelo , Carolina Fernandez , Ignacio Manzanares
发明人： Maria Flores , Andres Francesh , Pilar Gallego , Jose Luis Chicharro , Maria Zarzuelo , Carolina Fernandez , Ignacio Manzanares
IPC分类号： C07D241/36 , A61K31/495 , A01N43/60
CPC分类号： C07D515/22
摘要： This invention relates to antitumoral ecteinascidin derivatives that contain a fused ecteinascidin five ring system with a 1,4-bridge having the structure of formula (VIa) or (VIb) as described herein and compounds in which the —NH2 or —OH of the 1,4-bridge is derivatized, and related pharmaceutical compositions and methods. Such ecteinascidin derivatives include, but are not limited to, those compounds having formula (XVIIb): in which R1 and R4 together form a group of formula (VIa) or (VIb) as described herein, and R5, R7, R8, R14a, R14b, R15, and R21 are as defined herein.
摘要翻译：本发明涉及含有具有如本文所述的结构式（VIa）或（VIb）的1,4桥的融合的ecteinidinidin五环系统的抗肿瘤抗坏血酸衍生物，其中1或2的-NH 2或-OH的化合物，4桥衍生化，相关药物组成和方法。这样的黑皮质素衍生物包括但不限于具有式（XVIIb）的那些化合物：其中R 1和R 4一起形成本文所述的式（VIa）或（VIb）基团，并且R5，R7，R8，R14a， R14b，R15和R21如本文所定义。

3. 发明授权

US07524956B2 Hemisynthetic method and new compounds 有权
标题翻译：半合成方法和新化合物
公开(公告)号：US07524956B2
公开(公告)日：2009-04-28
申请号：US11774890
申请日：2007-07-09
申请人： Carmen Cuevas , Marta Perez , Andres Francesch , Carolina Fernandez , Jose Luis Chicharro , Pilar Gallego , Maria Zarzuelo , Fernando de Calle , Ignacio Manzanares
发明人： Carmen Cuevas , Marta Perez , Andres Francesch , Carolina Fernandez , Jose Luis Chicharro , Pilar Gallego , Maria Zarzuelo , Fernando de Calle , Ignacio Manzanares
IPC分类号： C07D471/22 , C07D487/22 , A61K31/496
CPC分类号： C07D471/18 , C07D471/22 , C07D491/22 , C07D515/22 , Y02P20/55
摘要： Methods are provided for preparing a compound with a fused ring structure of formula (XIV) which comprises one or more reactions starting from a 21-cyano compound of formula (XVI) where typically; R1 is an amidomethylene group or an acyloxymethylene group; R5 and R8 are independently chosen from —H, —OH or —OCOCH2OH, or R5 and R8 are both keto and the ring A is a p-benzoquinone ring; R14a and R14b are both —H ozone is —H and the other is —OH, —OCH3 or —OCH2CH3, or R14a and R14b together form a keto group; and R15 and R18 are independently chosen from —H or —OH, or R5 and R8 are both keto and the ring A is a p-benzoquinone ring. In modified starting materials, the 21-cyano group can be replaced by other groups introduced using nucleophilic reagents.
摘要翻译：提供了制备具有式（XIV）的稠环结构的化合物的方法，其包含一个或多个由式（XVI）的21-氰基化合物开始的反应，其中通常; R1是酰亚胺基或酰氧基亚甲基; R5和R8独立地选自-H，-OH或-OCOCH2OH，或R5和R8均为酮基，环A为对苯醌环; R14a和R14b都是-H-臭氧是-H而另一个是-OH，-OCH 3或-OCH 2 CH 3，或者R 14a和R 14b一起形成酮基; R 15和R 18独立地选自-H或-OH，或者R 5和R 8均为酮基，环A为对苯醌环。在改性原料中，21-氰基可以被其它使用亲核试剂引入的基团所取代。

4. 发明授权

US07241892B1 Hemisynthetic method and new compounds 有权
标题翻译：半合成方法和新化合物
公开(公告)号：US07241892B1
公开(公告)日：2007-07-10
申请号：US09979404
申请日：2000-05-15
申请人： Carmen Cuevas , Marta Perez , Andres Francesch , Carolina Fernandez , Jose Luis Chicharro , Pilar Gallego , Maria Zarzuelo , Fernando de la Calle , Ignacio Manzanares
发明人： Carmen Cuevas , Marta Perez , Andres Francesch , Carolina Fernandez , Jose Luis Chicharro , Pilar Gallego , Maria Zarzuelo , Fernando de la Calle , Ignacio Manzanares
IPC分类号： C07D471/14 , C07D515/22
CPC分类号： C07D471/18 , C07D471/22 , C07D491/22 , C07D515/22 , Y02P20/55
摘要： Methods are provided for preparing a compound with a fused ring structure of formula (XIV) which comprises one or more reactions starting from a 21-cyano compound of formula (XVI) where typically: R1 is an amidomethylene group or an acyloxymethylene group; R5 and R8 are independently chosen from —H, —OH or —OCOCH2OH, or R5 and R8 are both keto and the ring A is a p-benzoquinone ring; R14a and R14b are both —H ozone is —H and the other is —OH, —OCH3 or —OCH2CH3, or R14a and R14b together form a keto group; and R15 and R18 are independently chosen from —H or —OH, or R5 and R8 are both keto and the ring A is a p-benzoquinone ring. In modified starting materials, the 21-cyano group can be replaced by other groups introduced using nucleophilic reagents.
摘要翻译：提供了制备具有式（XIV）的稠环结构的化合物的方法，其包含一种或多种由式（XVI）的21-氰基化合物开始的反应，其中通常：R 1是亚氨基亚甲基基团或酰氧基亚甲基; R 5和R 8独立地选自-H，-OH或-OCOCH 2 OH，或R 5 O >和R 8均为酮，环A为对苯醌环; R 14a和R 14b都是-H臭氧是-H，另一个是-OH，-OCH 3或-OCH 3 2 3，或R 14a和R 14b共同形成酮基; R 15和R 18独立地选自-H或-OH，或R 5和R 8，都是酮基，环A是对苯醌环。在改性原料中，21-氰基可以被其它使用亲核试剂引入的基团所取代。

5. 发明授权

US07202361B2 Antitumoral ecteinascidin derivatives 有权
标题翻译：抗肿瘤抗坏血酸衍生物
公开(公告)号：US07202361B2
公开(公告)日：2007-04-10
申请号：US10240963
申请日：2001-04-12
申请人： Maria Flores , Andrés Francesch , Pilar Gallego , José Luis Chicharro , Maria Zarzuelo , Carolina Fernández , Ignacio Manzanares
发明人： Maria Flores , Andrés Francesch , Pilar Gallego , José Luis Chicharro , Maria Zarzuelo , Carolina Fernández , Ignacio Manzanares
IPC分类号： C07D515/22 , A61K31/395 , A61P35/00
CPC分类号： C07D515/22
摘要： This invention relates to compounds of the formula: wherein: the substituent groups defined by R1, R2 are each independently selected of H, C(═O)R′, C1–C18 alkyl, C2–C18 alkenyl, C2–C18 alkynyl, or aryl; each of the R′ groups is independently selected from the group consisting of H; OH; NO2; NH2; SH; CN; halogen; ═O; C(═O)H; C(═O)CH3; CO2H; or C1–C18 alkyl, C2–C18 alkenyl, C2–C18 alkynyl, or aryl, each of which, independently, may be substituted with one or more substituents selected from the group consisting of halogen, cyano, hydroxy, nitro, azido; alkanoyl, carboxamido, alkyl, alkenyl, alkynyl, aryloxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, aminoalkyl, carbocylic aryl having 6 or more carbons, and aralkyl; X2 is OX1 or N(X1)2 wherein each X1 is independently H, C(═O)R′ where R′ is as defined, C1–C18 alkyl, C2–C18 alkenyl, C2–C18 alkynyl, aryl, alkoxy, heterocyclyl, or two X1 groups together form a cyclic substituent on the nitrogen atom, or X1 is SO2CH3 when X2 is OX1, or N(X1)2 is NHCOalkylCOOH, Nilbiotin, NH(aa)y where aa is amino acid acyl andy is 1, 2 or 3 optionally with a amide terminal group, protected NHCOCH(NH2)CH2SH, NHCOalkenylaryl substituted with CF3, or m-methoxycarbonylbenzoylNH; wherein N(X1)2 is not NH2; X3 is selected of OR1 where R1 is as defined, CN, (═O), or H; X4 is—H or C1–C18 alkyl; and X5 is selected of H, or R1 where R1 is as defined; provided that the compound is not ecteinascidin 583 or 597, which are useful for treating tumors.
摘要翻译：本发明涉及下式的化合物：其中：R 1，R 2定义的取代基各自独立地选自H，C（.dbd.O）R'，C C 18 -C 18烷基，C 2 -C 18烯基，C 2 -C 18炔基或芳基; 每个R'基团独立地选自H; 哦; NO2; NH2; SH; CN; 卤素; .dbd.O; C（.dbd.O）H; C（.dbd.O）CH 3; CO 2，或C 1 -C 18烷基，C 2 -C 18烯基，C 2 -C 18炔基或芳基，其各自独立地可以被一个或多个选自卤素，氰基，羟基，硝基，叠氮基的取代基; 烷酰基，甲酰氨基，烷基，烯基，炔基，芳氧基，烷氧基，烷硫基，烷基亚磺酰基，烷基磺酰基，氨基烷基，具有6个或更多个碳的碳环芳基和芳烷基; X 2是OX 1或N（X 1）2，其中每个X 1独立地是H，C（.dbd.O）R'，其中R'如所定义，C 1 -C 18烷基，C 2 -C 18烯基，C 2 -C 18炔基，芳基，烷氧基，杂环基或两个X 1 一起在氮原子上形成环状取代基，或当X 2为O X 1或N（X 1）时，X 1为SO 2 CH 3。 sub.2是NHCO烷基COOH，NHBiotin，NH（aa），其中aa是氨基酸酰基，Y是1,2或3，任选具有酰胺末端基，保护的NHCOCH（NH 2）CH 2。 2S，被CF 3取代的NHCO烯基芳基或间甲氧基羰基苯甲酰基NH; 其中N（X 1）2不是NH 2; X 3选自OR.sub.1其中R 1如定义，CN，（.dbd.O）或H; X 4是-H或C 1 -C 18烷基; 并且X 5选自H或R 1，其中R 1如定义; 条件是该化合物不是用于治疗肿瘤的角叉菜胶583或597。

6. 发明申请

US20060111570A1 Synthetic process for the manufacture of an ecteinaschidin compound 有权
标题翻译：用于制造电球蛋白化合物的合成方法
公开(公告)号：US20060111570A1
公开(公告)日：2006-05-25
申请号：US11249172
申请日：2005-10-11
申请人： Andres Francesch , Carolina Fernandez , Jose Chicharro , Pilar Gallego , Maria Zarzuelo , Ignacio Manzanares , Marta Perez , Carmen Cuevas , Maria Martin , Simon Munt
发明人： Andres Francesch , Carolina Fernandez , Jose Chicharro , Pilar Gallego , Maria Zarzuelo , Ignacio Manzanares , Marta Perez , Carmen Cuevas , Maria Martin , Simon Munt
IPC分类号： C07D498/14
CPC分类号： C07D471/18 , C07D471/22 , C07D491/22 , C07D515/22
摘要： Processes are provided for preparing compounds with a fused ring structure of formula (XIV). Such products include ecteinascidins and have a spiroamine-1,4-bridge. The process involving forming a 1,4 bridge using a 1-labile, 10-hydroxy, 18-protected hydroxyl, di-6,8-en-5-one fused ring compound. After formation of the 1,4 brige, C-18 protection is removed before spiroamine introduction.
摘要翻译：提供了制备具有式（XIV）的稠环结构的化合物的方法。这些产品包括海马神经氨酸，并具有螺胺-1,4-桥。涉及使用1-不稳定的10-羟基，18-保护的羟基，二-6,8-烯-5-酮稠环化合物形成1,4桥的方法。形成1,4格氏之后，在引入螺环胺之前，C-18保护被去除。

7. 发明申请

US20080045713A1 Hemisynthetic Method and New Compounds 有权
标题翻译：半合成方法和新化合物
公开(公告)号：US20080045713A1
公开(公告)日：2008-02-21
申请号：US11774890
申请日：2007-07-09
申请人： Carmen Cuevas , Marta Perez , Andres Francesch , Carolina Fernandez , Jose Chicharro , Pilar Gallego , Maria Zarzuelo , Fernando Calle , Ignacio Manzanares
发明人： Carmen Cuevas , Marta Perez , Andres Francesch , Carolina Fernandez , Jose Chicharro , Pilar Gallego , Maria Zarzuelo , Fernando Calle , Ignacio Manzanares
IPC分类号： C07D471/08 , C07D491/147
CPC分类号： C07D471/18 , C07D471/22 , C07D491/22 , C07D515/22 , Y02P20/55
摘要： Methods are provided for preparing a compound with a fused ring structure of formula (XIV) which comprises one or more reactions starting from a 21-cyano compound of formula (XVI) where typically; R1 is an amidomethylene group or an aryloxymethylene group; R5 and R8 are independently chosen from —H, —OH or —OCOCH2OH, or R5 and R8 are both keto and the ring A is a p-benzoquinone ring; R14a and R14b are both —H ozone is —H and the other is —OH, —OCH3 or —OCH2CH3, or R14a and R14b together form a keto group; and R15 and R18 are independently chosen from —H or —OH, or R5 and R8 are both keto and the ring A is a p-benzoquinone ring. In modified starting materials, the 21-cyano group can be replaced by other groups introduced using nucleophilic reagents.
摘要翻译：提供了制备具有式（XIV）的稠环结构的化合物的方法，其包含一个或多个由式（XVI）的21-氰基化合物开始的反应，其中通常; R 1是酰亚胺基或芳氧基亚甲基; R 5和R 8独立地选自-H，-OH或-OCOCH 2 OH，或R 5 O >和R 8均为酮，环A为对苯醌环; R 14a和R 14b都是-H臭氧是-H，另一个是-OH，-OCH 3或-OCH 3 2 3，或R 14a和R 14b共同形成酮基; R 15和R 18独立地选自-H或-OH，或R 5和R 8，都是酮基，环A是对苯醌环。在改性原料中，21-氰基可以被其它使用亲核试剂引入的基团所取代。

8. 发明授权

US07420051B2 Synthetic process for the manufacture of an ecteinaschidin compound 有权
标题翻译：用于制造电球蛋白化合物的合成方法
公开(公告)号：US07420051B2
公开(公告)日：2008-09-02
申请号：US11249172
申请日：2005-10-11
申请人： Andrés Francesch , Carolina Fernández , José Luis Chicharro , Pilar Gallego , Maria Zarzuelo , Ignacio Manzanares , Marta Perez , Carmen Cuevas , María Jes{dot over (u)}s Martin , Simon Munt
发明人： Andrés Francesch , Carolina Fernández , José Luis Chicharro , Pilar Gallego , Maria Zarzuelo , Ignacio Manzanares , Marta Perez , Carmen Cuevas , María Jes{dot over (u)}s Martin , Simon Munt
IPC分类号： C07D267/22 , C07D281/18 , C07D291/00 , C07D337/16 , C07D487/00
CPC分类号： C07D471/18 , C07D471/22 , C07D491/22 , C07D515/22
摘要： Processes are provided for preparing compounds with a fused ring structure of formula (XIV). Such products include ecteinascidins and have a spiroamine-1,4-bridge. The process involving forming a 1,4 bridge using a 1-labile, 10-hydroxy, 18-protected hydroxyl, di-6,8-en-5-one fused ring compound. After formation of the 1,4 brige, C-18 protection is removed before spiroamine introduction.
摘要翻译：提供了制备具有式（XIV）的稠环结构的化合物的方法。这些产品包括海马神经氨酸，并具有螺胺-1,4-桥。涉及使用1-不稳定的10-羟基，18-保护的羟基，二-6,8-烯-5-酮稠环化合物形成1,4桥的方法。形成1,4格氏之后，在引入螺环胺之前，C-18保护被去除。

9. 发明申请

US20060106021A1 New antitumoral derivatives of et-743 有权
标题翻译： et-743的新抗肿瘤衍生物
公开(公告)号：US20060106021A1
公开(公告)日：2006-05-18
申请号：US10484060
申请日：2002-07-17
申请人： Valentin Martinez , Maria Flores , Pilar Gallego , Carmen Cuevas , Simon Munt , Ignacio Manzanares
发明人： Valentin Martinez , Maria Flores , Pilar Gallego , Carmen Cuevas , Simon Munt , Ignacio Manzanares
IPC分类号： A61K31/519 , C07D498/14
CPC分类号： C07D515/22
摘要： Derivatives of Et-743 or Et-770 or Et-729 are provided. The derivatives are of the general formula (Ia) wherein the substituent groups take various permitted meanings.
摘要翻译：提供Et-743或Et-770或Et-729的衍生物。衍生物具有通式（Ia），其中取代基具有各种允许的含义。

10. 发明授权

US08076337B2 Antitumoral derivatives of ET-743 有权
标题翻译： ET-743的抗肿瘤衍生物
公开(公告)号：US08076337B2
公开(公告)日：2011-12-13
申请号：US12755218
申请日：2010-04-06
申请人： Valentin Martinez , Maria Flores , Pilar Gallego , Carmen Cuevas , Simon Munt , Ignacio Manzanares
发明人： Valentin Martinez , Maria Flores , Pilar Gallego , Carmen Cuevas , Simon Munt , Ignacio Manzanares
IPC分类号： A01N43/58 , A01N43/60 , A61K31/50 , A61K31/495 , C07D241/36
CPC分类号： C07D515/22
摘要： Derivatives of Et-743 or Et-770 or Et-729 are provided. The derivatives are of the general formula Ia.: wherein the substituent groups take various permitted meanings.
摘要翻译：提供Et-743或Et-770或Et-729的衍生物。衍生物具有通式Ia：其中取代基具有各种允许的含义。

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