公开(公告)号：US08598145B2

公开(公告)日：2013-12-03

申请号：US12922525

申请日：2009-03-16

申请人： Stephen John Ralph ,  Jiri Neuzil

发明人： Stephen John Ralph ,  Jiri Neuzil

IPC分类号： A01N57/00 ,  A61K31/665 ,  C07F9/06 ,  C12N5/00 ,  C12N5/02

CPC分类号： C07F9/65522 ,  A61K31/355 ,  A61K47/54 ,  A61K47/551 ,  C07D311/72

摘要： This invention relates to anti-cancer compounds and to methods for treating or preventing cancer. In one aspect the invention concerns mitochondrially delivered pro-oxidant anti-cancer compounds that generate reactive oxygen species and induce apoptosis of cancerous cells. The delivery moiety can be a lipophilic cation and the pro-oxidant vitamin E analogue, such as α-tocopheryl succinate, α-tocopheryl maleate, α-tocopheryl maleyl amide, or 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)-chroman-6-yloxyacetic acid (α-tocopheryloxyacetic acid).

摘要翻译： 本发明涉及抗癌化合物以及治疗或预防癌症的方法。 一方面，本发明涉及线粒体递送的促氧化剂部分可以是产生活性氧物质并诱导癌细胞凋亡的促氧化剂抗癌化合物。 递送部分可以是亲脂性阳离子和促氧化维生素E类似物，例如琥珀酸α-生育酚酯，马来酸α-生育酚酯，α-生育酚基马来酰胺酰胺或2,5,7,8-四甲基-2R-（4R ，8R，12-三甲基十三烷基） - 苯并二氢吡喃-6-基氧基乙酸（α-生育酚乙酸）。

公开(公告)号：US20110105437A1

公开(公告)日：2011-05-05

申请号：US12922525

申请日：2009-03-16

申请人： Stephen John Ralph ,  Jiri Neuzil

发明人： Stephen John Ralph ,  Jiri Neuzil

IPC分类号： A61K31/665 ,  C07F9/655 ,  C12N5/09 ,  A61P35/00

CPC分类号： C07F9/65522 ,  A61K31/355 ,  A61K47/54 ,  A61K47/551 ,  C07D311/72

摘要： This invention relates to anti-cancer compounds and to methods for treating or preventing cancer. In one aspect the invention concerns mitochondrially delivered pro-oxidant anti-cancer compounds that generate reactive oxygen species and induce apoptosis of cancerous cells. The delivery moiety can be a lipophilic cation and the pro-oxidant vitamin E analogue, such as α-tocopheryl succinate, α-tocopheryl maleate, α-tocopheryl maleyl amide, or 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)-chroman-6-yloxyacetic acid (α-tocopheryloxyacetic acid).

摘要翻译： 本发明涉及抗癌化合物以及治疗或预防癌症的方法。 一方面，本发明涉及产生活性氧物质并诱导癌细胞凋亡的线粒体递送的促氧化剂抗癌化合物。 递送部分可以是亲脂性阳离子和促氧化维生素E类似物，例如琥珀酸α-生育酚酯，马来酸α-生育酚酯，α-生育酚基马来酰胺酰胺或2,5,7,8-四甲基-2R-（4R ，8R，12-三甲基十三烷基） - 苯并二氢吡喃-6-基氧基乙酸（α-生育酚乙酸）。

公开(公告)号：US20110059898A1

公开(公告)日：2011-03-10

申请号：US12441487

申请日：2007-09-17

申请人： Stephen John Ralph ,  Jiri Neuzil

发明人： Stephen John Ralph ,  Jiri Neuzil

IPC分类号： A61K38/08 ,  A61K31/355 ,  A61P35/00 ,  G01N33/53 ,  C07D311/72 ,  G06G7/48

CPC分类号： A61K31/355 ,  G01N33/5079 ,  G01N33/82

摘要： This invention relates to anti-cancer compounds and to methods for treating or preventing cancer. In particular, the invention concerns pro-oxidant anti-cancer compounds, such as pro-oxidant forms of vitamin E, that selectively interact with complex II of the mitochondrial respiratory chain of cancerous cells, generate reactive oxygen species and induce apoptosis of those cells.

摘要翻译： 本发明涉及抗癌化合物以及治疗或预防癌症的方法。 特别地，本发明涉及与氧化剂形成的维生素E的促氧化剂抗癌化合物，其选择性地与癌细胞线粒体呼吸链的复合物II相互作用，产生活性氧并诱导细胞凋亡。

公开(公告)号：US09896466B2

公开(公告)日：2018-02-20

申请号：US14786710

申请日：2014-04-07

申请人： Smart Brain S.R.O. ,  Biotechnologicky Ustav Av Cr, V.V.I. ,  Jiri Neuzil ,  KKCG AG

发明人： Jiri Neuzil ,  Jan Stursa ,  Lukas Werner

IPC分类号： C07F9/54 ,  A61K31/135

CPC分类号： C07F9/5456 ,  C07F9/5442 ,  C07F9/5449

摘要： The subject of the invention are new mitochondrially targeted E/Z isomers of aliphatic triphenylphosphonium derivatives of tamoxifen where the aliphatic chain is alkyl or alkenyl, and their corresponding tertiary amine salts and/or their mixture (MitoTAX). Alkyl triphenylphosphonium derivatives of tamoxifen have the general formula (I), where n=8 to 12 and where Z is selected from the group of organic salts or inorganic salts. Alkenyl triphenylphosphonium derivatives of tamoxifen have the general formula IA, where n=6 to 10 and where Z has the above mentioned meaning. These compounds are applicable for the treatment of neoplastic disease, especially those with high HER2 protein levels. The drug for the treatment of neoplastic diseases according to the invention contains at least one E/Z isomer of aliphatic triphenylphosphonium derivatives of tamoxifen of the general formula (I) and/or IA or their corresponding salts of tertiary amine.

公开(公告)号：US08410056B2

公开(公告)日：2013-04-02

申请号：US12441487

申请日：2007-09-17

申请人： Stephen John Ralph ,  Jiri Neuzil

发明人： Stephen John Ralph ,  Jiri Neuzil

IPC分类号： A61P43/00

CPC分类号： A61K31/355 ,  G01N33/5079 ,  G01N33/82

摘要： This invention relates to anti-cancer compounds and to methods for treating or preventing cancer. In particular, the invention concerns pro-oxidant anti-cancer compounds, such as pro-oxidant forms of vitamin E that selectively interact with complex II of the mitochondrial respiratory chain of cancerous cells, generate reactive oxygen species and induce apoptosis of those cells.

摘要翻译： 本发明涉及抗癌化合物以及治疗或预防癌症的方法。 特别地，本发明涉及促氧化剂抗癌化合物，例如与癌细胞的线粒体呼吸链的复合物II选择性相互作用的维生素E的促氧化剂形式，产生活性氧物质并诱导那些细胞的凋亡。

公开(公告)号：US20100260830A1

公开(公告)日：2010-10-14

申请号：US12755649

申请日：2010-04-07

申请人： Brian A Salvatore ,  Jaroslav Turanek ,  Jiri Neuzil

发明人： Brian A Salvatore ,  Jaroslav Turanek ,  Jiri Neuzil

IPC分类号： A61K9/127 ,  A61K31/355 ,  A61P35/00

CPC分类号： A61K31/355 ,  A61K9/1272 ,  A61K9/19

摘要： Formulations of N-chroman dicarboxylic acid derivatives and their bioisosteres in liposomal systems. Lyophilized liposomal dosage forms of N-chromans, are found to be stable, to achieve therapeutically meaningful plasma levels on administration to a mammalian host, and to demonstrate selective pro-apoptotic oncolytic properties in vivo. Advantageously, these formulations overcome the systemic toxicity that characterized their administration by other dosage forms.

摘要翻译： 脂质体系中N-苯并二氢吡喃二羧酸衍生物及其生物电子等排体的制备。 发现N-苯并二氢吡喃染色体的冻干脂质体剂型是稳定的，以在哺乳动物宿主施用时达到治疗上有意义的血浆水平，并且在体内证明选择性促凋亡的溶瘤性质。 有利地，这些制剂克服了其通过其它剂型给药的特征的全身毒性。