公开(公告)号：US07498340B2

公开(公告)日：2009-03-03

申请号：US11783495

申请日：2007-04-10

申请人： Mauro Marzi ,  Domenico Alloatti ,  Claudio Pisano ,  Maria Ornella Tinti ,  Loredana Vesci ,  Franco Zunino

发明人： Mauro Marzi ,  Domenico Alloatti ,  Claudio Pisano ,  Maria Ornella Tinti ,  Loredana Vesci ,  Franco Zunino

IPC分类号： A61K31/4745 ,  C07D491/22

CPC分类号： C07D491/22

摘要： Formula (I) compounds are described: (I) where the groups are as defined in the description here below, the racemic mixtures, their individual enantiomers, their individual diastereoisomers, their mixtures, and their pharmaceutically acceptable salts. Said compounds are topoisomerase I inhibitors.

摘要翻译： 描述了式（I）化合物：其中基团如下文所述的定义，外消旋混合物，其各自的对映异构体，其各自的非对映异构体，它们的混合物及其药学上可接受的盐。 所述化合物是拓扑异构酶I抑制剂。

公开(公告)号：US07705012B2

公开(公告)日：2010-04-27

申请号：US11596015

申请日：2005-05-04

申请人： Claudio Pisano ,  Giuseppe Giannini ,  Maria Ornella Tinti ,  Loredana Vesci ,  Domenico Alloatti ,  Sergio Penco ,  Alma Dal Pozzo ,  Ni Minghong ,  Sabrina Dallavalle ,  Lucio Merlini ,  Franco Zunino

发明人： Claudio Pisano ,  Giuseppe Giannini ,  Maria Ornella Tinti ,  Loredana Vesci ,  Domenico Alloatti ,  Sergio Penco ,  Alma Dal Pozzo ,  Ni Minghong ,  Sabrina Dallavalle ,  Lucio Merlini ,  Franco Zunino

IPC分类号： A61K31/4745 ,  C07D491/22

CPC分类号： C07K7/52 ,  A61K38/00

摘要： Compounds of Formula (I) are described in which the R1 group is as defined in the specification and includes the condensation of the camptothecin molecule in position 7 with a cyclopeptide containing the RGD sequence. Said compounds are endowed both with high affinity for integrin receptors αvβ3 and αvβ5 and with selective cytotoxic activity on human tumour cell lines at micromolar concentrations.

摘要翻译： 描述了式（I）的化合物，其中R 1基团如说明书中所定义，并且包括7位的喜树碱分子与含有RGD序列的环肽的缩合。 所述化合物对整联蛋白受体αv＆bgr 3和αv＆bgr 5具有高亲和力，并且在微摩尔浓度下对人肿瘤细胞系具有选择性细胞毒性活性。

公开(公告)号：US20070232639A1

公开(公告)日：2007-10-04

申请号：US11596189

申请日：2005-05-04

申请人： Claudio Pisano ,  Giuseppe Giannini ,  Maria Ornella Tinti ,  Loredana Vesci ,  Domenico Alloatti ,  Sergio Penco ,  Alma Dal Pozzo ,  Ni Minghong ,  Sabrina Dallavalle ,  Lucio Merlini ,  Franco Zunino

发明人： Claudio Pisano ,  Giuseppe Giannini ,  Maria Ornella Tinti ,  Loredana Vesci ,  Domenico Alloatti ,  Sergio Penco ,  Alma Dal Pozzo ,  Ni Minghong ,  Sabrina Dallavalle ,  Lucio Merlini ,  Franco Zunino

IPC分类号： A61K31/437 ,  A61K31/4375 ,  C07D405/14

CPC分类号： A61K47/64

摘要： Compounds or formula (I) are described, in which the R and R1 groups are as defined here below and include the condensation of the camptothecin molecule in position 20 with a cyclopeptide containing the RGD sequence. Said compounds are endowed both with high affinity for integrin receptors αvβ3 and αvβ5 and with selective cytotoxic activity on human tumour cell lines at micromolar concentrations.

摘要翻译： 描述了化合物或式（I），其中R和R 1个基团如下文所定义，并且包括20位的喜树碱分子与含有RGD序列的环肽的缩合。 所述化合物赋予对整联蛋白受体α和β5β5的高亲和力，并与 在微摩尔浓度下对人肿瘤细胞系的选择性细胞毒活性。

公开(公告)号：US07589099B2

公开(公告)日：2009-09-15

申请号：US11596016

申请日：2005-04-28

申请人： Claudio Pisano ,  Giuseppe Giannini ,  Loredana Vesci ,  Domenico Alloatti ,  Sergio Penco ,  Alma Dal Pozzo ,  Ni Ming Hong ,  Sabrina Dallavalle ,  Lucio Merlini ,  Maria Ornella Tinti ,  Franco Zunino

发明人： Claudio Pisano ,  Giuseppe Giannini ,  Loredana Vesci ,  Domenico Alloatti ,  Sergio Penco ,  Alma Dal Pozzo ,  Ni Ming Hong ,  Sabrina Dallavalle ,  Lucio Merlini ,  Maria Ornella Tinti ,  Franco Zunino

IPC分类号： A61K31/4745 ,  C07D491/22

CPC分类号： A61K47/64

摘要： Compounds of Formula (I) are described: in which the R1 group is as defined in the specification and includes the condensation of 7-t-butoxyiminomethylcamptothecin in position 20 with a cyclopeptide containing the RGD sequence. Said compounds are endowed both with high affinity for integrin receptors αvβ3 and αvβ5 and with selective cytotoxic activity on human tumour cell lines at micromolar concentrations.

摘要翻译： 描述式（I）的化合物：其中R 1基团如本说明书中所定义，并且包括位置20上的7-叔丁氧基亚氨基甲基喜树碱与含有RGD序列的环肽的缩合。 所述化合物赋予对整联蛋白受体alphavbeta3和alphavbeta5的高亲和力，并且在微摩尔浓度下对人肿瘤细胞系具有选择性细胞毒性活性。

公开(公告)号：US20070213353A1

公开(公告)日：2007-09-13

申请号：US11783495

申请日：2007-04-10

申请人： Mauro Marzi ,  Domenico Alloatti ,  Claudio Pisano ,  Maria Tinti ,  Loredana Vesci ,  Franco Zunino

发明人： Mauro Marzi ,  Domenico Alloatti ,  Claudio Pisano ,  Maria Tinti ,  Loredana Vesci ,  Franco Zunino

IPC分类号： A61K31/4745 ,  C07D491/14

CPC分类号： C07D491/22

摘要： Formula (I) compounds are described: (I) where the groups are as defined in the description here below, the racemic mixtures, their individual enantiomers, their individual diastereoisomers, their mixtures, and their pharmaceutically acceptable salts. Said compounds are topoisomerase I inhibitors.

摘要翻译： 描述了式（I）化合物：其中基团如下文所述的定义，外消旋混合物，其各自的对映异构体，其各自的非对映异构体，它们的混合物及其药学上可接受的盐。 所述化合物是拓扑异构酶I抑制剂。

公开(公告)号：US20080033003A1

公开(公告)日：2008-02-07

申请号：US11596015

申请日：2005-05-04

申请人： Claudio Pisano ,  Giuseppe Giannini ,  Maria Omella Tinti ,  Loredana Vesci ,  Domenico Alloatti ,  Sergio Penco ,  Alma Dal Pozzo ,  Ni Minghong ,  Sabrina Dallavalle ,  Lucio Merlini ,  Franco Zunino

发明人： Claudio Pisano ,  Giuseppe Giannini ,  Maria Omella Tinti ,  Loredana Vesci ,  Domenico Alloatti ,  Sergio Penco ,  Alma Dal Pozzo ,  Ni Minghong ,  Sabrina Dallavalle ,  Lucio Merlini ,  Franco Zunino

IPC分类号： A61K31/436 ,  A61P31/12 ,  A61P33/00 ,  A61P35/00 ,  A61P35/04

CPC分类号： C07K7/52 ,  A61K38/00

摘要： Compounds of Formula (I) are described in which the R1 group is as defined in the specification and includes the condensation of the camptothecin molecule in position 7 with a cyclopeptide containing the RGD sequence. Said compounds are endowed both with high affinity for integrin receptors αvβ3 and αvβ5 and with selective cytotoxic activity on human tumour cell lines at micromolar concentrations.

摘要翻译： 描述了式（I）的化合物，其中R 1 H 1基团如说明书中所定义，并且包括位置7上的喜树碱分子与含有RGD序列的环肽的缩合。 所述化合物赋予对整联蛋白受体α和β5β5的高亲和力，并与 在微摩尔浓度下对人肿瘤细胞系的选择性细胞毒活性。

公开(公告)号：US07452900B2

公开(公告)日：2008-11-18

申请号：US10512094

申请日：2003-05-28

申请人： Mauro Marzi ,  Domenico Alloatti ,  Caludio Pisano ,  Maria Ornella Tinti ,  Vesci Loredana ,  Zunino Franco

发明人： Mauro Marzi ,  Domenico Alloatti ,  Caludio Pisano ,  Maria Ornella Tinti ,  Vesci Loredana ,  Zunino Franco

IPC分类号： A61K31/4738 ,  C07D491/22

CPC分类号： C07D491/22

摘要： Formula (I) compounds are described: (I) where the groups are as defined in the description here below, the racemic mixtures, their individual enantiomers, their individual diastereoisomers, their mixtures, and their pharmaceutically acceptable salts. Said compounds are topoisomerase I inhibitors.

摘要翻译： 描述了式（I）化合物：其中基团如下文所述的定义，外消旋混合物，其各自的对映异构体，其各自的非对映异构体，它们的混合物及其药学上可接受的盐。 所述化合物是拓扑异构酶I抑制剂。

公开(公告)号：US07572778B2

公开(公告)日：2009-08-11

申请号：US10563480

申请日：2004-07-06

申请人： Giuseppe Giannini ,  Domenico Alloatti ,  Marcella Marcellini ,  Mauro Marzi ,  Teresa Riccioni ,  Maria Ornella Tinti

发明人： Giuseppe Giannini ,  Domenico Alloatti ,  Marcella Marcellini ,  Mauro Marzi ,  Teresa Riccioni ,  Maria Ornella Tinti

IPC分类号： A61K31/66 ,  C07F9/02

CPC分类号： C07C217/84 ,  C07C43/23 ,  C07F9/12

摘要： The present invention is related to new derivatives of Combretastatin, of Formula obtained by total synthesis. The strategy developed for each of the compounds is to i) replace a halogen (i.e. fluorine atom) to hydrogen on olefinic bound; ii) replace an aromatic ring in a natural product with an amino-aromatic ring. Said compounds recognize and bind the tubulin site: are useful for treating pathological states which arise from or are exacerbated by cell proliferation—as anticancer and/or antiangiogenic activity, in a mammal—to pharmaceutical compositions comprising these compounds.

摘要翻译： 本发明涉及通过全合成获得的配方的Combretastatin的新衍生物。 为每种化合物开发的策略是i）在烯属结合物上取代卤素（即氟原子）至氢; ii）用天然产物中的芳族环与氨基 - 芳香环取代。 所述化合物识别并结合微管蛋白部位：可用于治疗在哺乳动物中由包含这些化合物的药物组合物中由细胞增殖引起或加剧的病理状态 - 作为抗癌和/或抗血管生成活性。

公开(公告)号：US20070225311A1

公开(公告)日：2007-09-27

申请号：US11596016

申请日：2005-04-28

申请人： Claudio Pisano ,  Giuseppe Giannini ,  Loredana Vesci ,  Domenico Alloatti ,  Sergio Penco ,  Alma Dal Pozzo ,  Ni Minghong ,  Sabrina Dallavalle ,  Lucio Merlini

发明人： Claudio Pisano ,  Giuseppe Giannini ,  Loredana Vesci ,  Domenico Alloatti ,  Sergio Penco ,  Alma Dal Pozzo ,  Ni Minghong ,  Sabrina Dallavalle ,  Lucio Merlini

IPC分类号： A61K31/435 ,  C07D405/14

CPC分类号： A61K47/64

摘要： Compounds of Formula (I) are described: in which the R1 group is as defined in the specification and includes the condensation of 7-t-butoxyiminomethylcamptothecin in position 20 with a cyclopeptide containing the RGD sequence. Said compounds are endowed both with high affinity for integrin receptors αvβ3 and αvβ5 and with selective cytotoxic activity on human tumour cell lines at micromolar concentrations.

摘要翻译： 描述了式（I）的化合物：其中R 1 H 1基团如说明书中所定义，并且包括位置20上的7-叔丁氧基亚氨基甲基喜树碱与含有RGD序列的环肽的缩合。 所述化合物赋予对整联蛋白受体α和β5β5的高亲和力，并与 在微摩尔浓度下对人肿瘤细胞系的选择性细胞毒活性。

公开(公告)号：US20060160778A1

公开(公告)日：2006-07-20

申请号：US10563480

申请日：2004-07-06

申请人： Giuseppe Giannini ,  Domenico Alloatti ,  Marcella Marcellini ,  Mauro Marzi ,  Teresa Riccioni ,  Maria Tinti

发明人： Giuseppe Giannini ,  Domenico Alloatti ,  Marcella Marcellini ,  Mauro Marzi ,  Teresa Riccioni ,  Maria Tinti

IPC分类号： A61K31/66 ,  C07F9/02 ,  A61K31/135

CPC分类号： C07C217/84 ,  C07C43/23 ,  C07F9/12

摘要： The present invention is related to new derivatives of Combretastatin, of Formula obtained by total synthesis. The strategy developed for each of the compounds is to i) replace a halogen (i.e. fluorine atom) to hydrogen on olefinic bound; ii) replace an aromatic ring in a natural product with an amino-aromatic ring. Said compounds recognize and bind the tubulin site: are useful for treating pathological states which arise from or are exacerbated by cell proliferation—as anticancer and/or antiangiogenic activity, in a mammal—to pharmaceutical compositions comprising these compounds.