公开(公告)号：US5288887A

公开(公告)日：1994-02-22

申请号：US978788

申请日：1992-11-19

申请人： Abdul R. Khokhar ,  Zahid H. Siddik ,  Salaam Al-Baker

发明人： Abdul R. Khokhar ,  Zahid H. Siddik ,  Salaam Al-Baker

IPC分类号： C07F15/00 ,  A61K31/28

CPC分类号： C07F15/0093

摘要： Platinum(IV) complexes with mixed carboxylato ligands having the formula: ##STR1## where X.sup.1 and X.sup.2 are carboxylato, or are jointly dicarboxylato, where .sup.1 Y and Y.sup.2 are carboxylato, and where Z is either diaminocyclohexane or ethylenediamine, have been found to have desirable antitumor activity, as well as relatively low levels of toxicity.

摘要翻译： 已经发现，铂（IV）络合物与具有下式的混合羧基配位体：其中X1和X2是羧基或羧基共轭二羧酸，其中Z是二氨基环己烷或乙二胺，其中Z是二氨基环己烷或乙二胺， 所需的抗肿瘤活性，以及​​较低的毒性水平。

公开(公告)号：US5434256A

公开(公告)日：1995-07-18

申请号：US316139

申请日：1994-09-30

申请人： Abdul R. Khokhar ,  Zahid H. Siddik

发明人： Abdul R. Khokhar ,  Zahid H. Siddik

IPC分类号： C07F15/00 ,  A61K31/555

CPC分类号： C07F15/0093

摘要： Novel 1,4 and 1,2-diaminocyclohexane platinum IV complexes have been synthesized that show activity in vivo against tumor models resistant to cis-platin and tetraplatin. The novel complexes include the chloro, acetate, trifluoroacetate, propionate, butyrate, pentanoate, hexanoate and heptanoate as leaving ligands and 1,4 or 1,2-DACH-amine ligands. The complexes showed good in vitro cytotoxic activity against murine leukemia L1210/0, L1210/DDP and L1210/DACH. High in vivo activity was shown against L1210 leukemia cells and against cis-platin resistant L1210/DDP. Excellent antitumor activity against M5076 was also exhibited by the new complexes. Additionally, the platinum complexes did not elicit any indication of nephrotoxicity in the in vivo tests.

摘要翻译： 已经合成了新的1,4和1,2-二氨基环己烷铂IV络合物，其在体内表现出对顺铂和四铂的抗肿瘤模型的活性。 新型络合物包括离开配体和1,4或1,2-DACH-胺配体的氯，乙酸酯，三氟乙酸酯，丙酸酯，丁酸酯，戊酸酯，己酸酯和庚酸酯。 该配合物对鼠白血病L1210 / 0，L1210 / DDP和L1210 / DACH显示出良好的体外细胞毒活性。 针对L1210白血病细胞和抗顺铂耐药性L1210 / DDP显示出高体内活性。 新配合物也展示了抗M5076的抗肿瘤活性。 此外，铂络合物在体内测试中没有引起肾毒性的任何迹象。

公开(公告)号：US07271161B2

公开(公告)日：2007-09-18

申请号：US10655657

申请日：2003-09-05

申请人： Zahid H. Siddik ,  Abdul R. Khokhar

发明人： Zahid H. Siddik ,  Abdul R. Khokhar

IPC分类号： A61P35/00 ,  A61K31/555 ,  A61K31/28 ,  C07D223/00 ,  C07D211/00

CPC分类号： C07F15/0093

摘要： The present invention concerns the use of methods and compositions for the treatment of cancer and other hyperproliferative diseases. In certain embodiments, methods are described for the treatment of cancer and/or hyperproliferative diseases by administration of compositions containing at least one platinum complex alone or in combination with a modulator of glutathione. In particular, the methods may be used to treat cisplatin or carboplatin resistant tumor cells.

摘要翻译： 本发明涉及用于治疗癌症和其它过度增生性疾病的方法和组合物的用途。 在某些实施方案中，描述了通过施用含有至少一种铂络合物单独或与谷胱甘肽调节剂组合的组合物来治疗癌症和/或过度增殖性疾病的方法。 特别地，该方法可用于治疗顺铂或卡铂抗性肿瘤细胞。

公开(公告)号：US5318962A

公开(公告)日：1994-06-07

申请号：US927201

申请日：1992-08-07

申请人： Abdul R. Khokhar ,  Zahid H. Siddik ,  Robert A. Newman

发明人： Abdul R. Khokhar ,  Zahid H. Siddik ,  Robert A. Newman

IPC分类号： C07F15/00 ,  A61K31/555

CPC分类号： C07F15/0093

摘要： Water-soluble complexes having the formula: ##STR1## and stereoisomers thereof, where Z.sup.1 and Z.sup.2 are halogens, and X.sup.1 and X.sup.2 are selected from the group consisting of sulfate, phosphate, nitrate, and monocarboxylate, or are jointly dicarboxylate, have been found to have desirable antitumor activity, as well as relatively low levels of toxicity.

摘要翻译： 具有下式的水溶性络合物及其立体异构体，其中Z1和Z2为卤素，X1和X2选自硫酸盐，磷酸盐，硝酸盐和单羧酸盐，或共同二羧酸盐。 具有期望的抗肿瘤活性，以及​​相对低的毒性水平。

公开(公告)号：US5393909A

公开(公告)日：1995-02-28

申请号：US200395

申请日：1994-02-23

申请人： Abdi R. Khokhar ,  Zahid H. Siddik

发明人： Abdi R. Khokhar ,  Zahid H. Siddik

IPC分类号： C07F15/00 ,  A61K31/28

CPC分类号： C07F15/0093

摘要： Novel 1,4-diaminocyclohexane platinum II and platinum IV complexes were synthesized which show activity in vivo against tumor models resistant to cis-platin and tetraplatin. The novel complexes include the sulfato, chloro, hydroxyl, acetato methylmalonato, tartronato and 1,1-cyclobutane dicarboxylato as leaving ligands and 1,4-DACH amine as non-leaving ligands. The complexes showed good in vitro cytotoxic activity against murine leukemia L1210/0 and human ovarian A2780 cell lines. High in vivo activity was shown against L1210 leukemia cells and against cis-platin resistant L1210/DDP and tetraplatin resistant L1210/DACH. Excellent antitumor activity against M5076 was also exhibited by the new complexes. Additionally, the platinum complexes did not elicit any indication of nephrotoxicity in the in vivo tests.

摘要翻译： 合成了新的1,4-二氨基环己烷铂II和铂IV络合物，其显示体内对顺铂和四铂的抗肿瘤模型的活性。 新型配合物包括离去配体的硫酸盐，氯代，羟基，丙酮酸，甲基丙二酸，乙酰丙酮酸和1,1-环丁烷二羧酸，作为非离去配体的1,4-丁基胺。 复合物对鼠白血病L1210 / 0和人卵巢A2780细胞系显示出良好的体外细胞毒活性。 针对L1210白血病细胞和针对顺铂耐药性L1210 / DDP和耐四氯化铂L1210 / DACH显示出高体内活性。 新配合物也展示了抗M5076的抗肿瘤活性。 此外，铂络合物在体内测试中没有引起肾毒性的任何迹象。