公开(公告)号：WO2012145069A2

公开(公告)日：2012-10-26

申请号：PCT/US2012/026609

申请日：2012-02-24

申请人： THE UNIVERSITY OF TOLEDO ,  MALTESE, William, A. ,  ERHARDT, Paul, W. ,  ROBINSON, Michael, W. ,  OVERMEYER, Jean, H.

发明人： MALTESE, William, A. ,  ERHARDT, Paul, W. ,  ROBINSON, Michael, W. ,  OVERMEYER, Jean, H.

IPC分类号： A61K31/4439

CPC分类号： A61K31/404 ,  A61K31/4439 ,  A61K45/06 ,  C07D209/08 ,  C07D209/12 ,  C07D401/06 ,  C07D403/06 ,  C40B40/04 ,  A61K2300/00

摘要： The present invention provides materials and methods to induce cell death by methuosis, a non-apoptotic cell death mechanism. Small molecules herein are useful for treating cell proliferation disorders or anomalies, particularly, but not exclusively, cancer. Methods related to the research and pharmaceutical use of the small molecules are also provided herein.

摘要翻译： 本发明提供了通过无细胞凋亡机制诱导细胞死亡的材料和方法。 本文中的小分子可用于治疗细胞增殖障碍或异常，特别是但不排他地是癌症。 本文还提供了与小分子的研究和药物应用相关的方法。

公开(公告)号：WO2004080412A2

公开(公告)日：2004-09-23

申请号：PCT/US2004/007269

申请日：2004-03-05

申请人： THE UNIVERSITY OF TOLEDO ,  ERHARDT, Paul, W. ,  KLIS, Weislaw, A. ,  SARVER, Jeffrey, G.

发明人： ERHARDT, Paul, W. ,  KLIS, Weislaw, A. ,  SARVER, Jeffrey, G.

IPC分类号： A61K

CPC分类号： A61K31/337 ,  A61K38/06 ,  A61K38/07 ,  A61K38/08 ,  A61K47/54 ,  A61K47/543 ,  A61K47/55 ,  A61K47/551 ,  A61K47/554 ,  A61K47/64

摘要： Methods and compositions for treating cancer patients that include administering at least one or more hybrid derivatives of paclitaxel that simultaneously display improved aqueous solubility, chemical stability under physiological conditions, a decreased liability toward multi-drug resistance, and in certain instances enhanced selective toxicity toward cancer cells compared to normal cells. The derivative, paclitaxel substituted with at least one or more polar appendages at either the 7- or 10- positions as defined by a formula "7-OR-10-OR'-paclitaxel", is either deployed alone or in 10 combination protocols with other chemotherapeutic agents.

摘要翻译： 用于治疗癌症患者的方法和组合物包括给予紫杉醇的至少一种或多种杂合衍生物，其同时显示改善的水溶性，生理条件下的化学稳定性，对多药耐药性的降低的责任，并且在某些情况下增强对癌症的选择性毒性 细胞与正常细胞相比。 在由式“7-OR-10-OR” - 紫杉醇“定义的7位或10位上用至少一种或多种极性附属物取代的衍生物紫杉醇或者单独部署或以10种组合方案 其他化疗剂。

公开(公告)号：WO2012145069A3

公开(公告)日：2014-04-24

申请号：PCT/US2012026609

申请日：2012-02-24

申请人： UNIV TOLEDO ,  MALTESE WILLIAM A ,  ERHARDT PAUL W ,  ROBINSON MICHAEL W ,  OVERMEYER JEAN H

发明人： MALTESE WILLIAM A ,  ERHARDT PAUL W ,  ROBINSON MICHAEL W ,  OVERMEYER JEAN H

IPC分类号： A01N43/78

CPC分类号： A61K31/404 ,  A61K31/4439 ,  A61K45/06 ,  C07D209/08 ,  C07D209/12 ,  C07D401/06 ,  C07D403/06 ,  C40B40/04 ,  A61K2300/00

摘要： The present invention provides materials and methods to induce cell death by methuosis, a non-apoptotic cell death mechanism. Small molecules herein are useful for treating cell proliferation disorders or anomalies, particularly, but not exclusively, cancer. Methods related to the research and pharmaceutical use of the small molecules are also provided herein.

摘要翻译： 本发明提供了通过无细胞凋亡机制诱导细胞死亡的材料和方法。 本文中的小分子可用于治疗细胞增殖障碍或异常，特别是但不排他地是癌症。 本文还提供了与小分子的研究和药物应用相关的方法。

公开(公告)号：WO2003030815A3

公开(公告)日：2003-04-17

申请号：PCT/US2002/030727

申请日：2002-09-27

申请人： UNIVERSITY OF TOLEDO, THE ,  ERHARDT, Paul, W. ,  KLIS, Weislaw, A. ,  SARVER, Jeffrey, G.

发明人： ERHARDT, Paul, W. ,  KLIS, Weislaw, A. ,  SARVER, Jeffrey, G.

IPC分类号： C07D305/14

摘要： A method for removing acyl-groups appended by an ester linkage to the 2'-hydroxyl group present in paclitaxel-related molecules comprising treatment with alcohol under non-acidic conditions. 2',7-bis-Monochloroacetylpaclitaxel analogs are converted to their corresponding 7-monochloroacetyl derivatives by treatment with alcohol under non-acidic conditions.

公开(公告)号：WO2009111428A2

公开(公告)日：2009-09-11

申请号：PCT/US2009/035803

申请日：2009-03-03

申请人： THE ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND ,  THE UNIVERSITY OF TOLEDO ,  XAVIER UNIVERSITY OF LOUISIANA ,  UNITED STATES DEPARTMENT OF AGRICULTURE ,  ERHARDT, Paul, W. ,  KHUPSE, Rahul, S. ,  SARVER, Jeffrey, G. ,  CLEVELAND, Thomas, E. ,  BOUE, Stephen, M. ,  WIESE, Thomas, E. ,  BUROW, Matthew, E. ,  MCLACHLAN, John, A.

发明人： ERHARDT, Paul, W. ,  KHUPSE, Rahul, S. ,  SARVER, Jeffrey, G. ,  CLEVELAND, Thomas, E. ,  BOUE, Stephen, M. ,  WIESE, Thomas, E. ,  BUROW, Matthew, E. ,  MCLACHLAN, John, A.

IPC分类号： A61M1/36

CPC分类号： C07D493/14

摘要： Two distinct methods are disclosed and claimed for synthesizing glyceollin I plus glyceollin II as a mixture and as their pure forms. Stereochemical isomers and various synthetic intermediates are also synthesized and claimed for their novel compositions of matter. All compounds and their mixtures are claimed for use in formulations that are useful to treat or prevent cancer, or that have utility as selective estrogen receptor modulators, such formulations including enhanced or medical foods, dietary supplements and ethical pharmaceutical agents.

摘要翻译： 公开并要求保护两种不同的方法用于合成作为混合物和作为其纯形式的甘油糖苷I加甘油二酯II。 立体化学异构体和各种合成中间体也被合成并要求其新颖的物质组成。 要求所有化合物及其混合物用于可用于治疗或预防癌症的制剂或可用作选择性雌激素受体调节剂的制剂，所述制剂包括增强或医疗食品，膳食补充剂和道德药物制剂。

公开(公告)号：WO2009111428A4

公开(公告)日：2010-01-28

申请号：PCT/US2009035803

申请日：2009-03-03

申请人： UNIV TULANE ,  UNIV TOLEDO ,  XAVIER UNIVERSITY OF LOUISIANA ,  US AGRICULTURE ,  ERHARDT PAUL W ,  KHUPSE RAHUL S ,  SARVER JEFFREY G ,  CLEVELAND THOMAS E ,  BOUE STEPHEN M ,  WIESE THOMAS E ,  BUROW MATTHEW E ,  MCLACHLAN JOHN A

发明人： ERHARDT PAUL W ,  KHUPSE RAHUL S ,  SARVER JEFFREY G ,  CLEVELAND THOMAS E ,  BOUE STEPHEN M ,  WIESE THOMAS E ,  BUROW MATTHEW E ,  MCLACHLAN JOHN A

IPC分类号： C07D493/02 ,  A61K31/353 ,  A61P5/24 ,  A61P35/00 ,  C07D311/04 ,  C07D311/74 ,  C07D493/14

CPC分类号： C07D493/14

摘要： Two distinct methods are disclosed and claimed for synthesizing glyceollin I plus glyceollin II as a mixture and as their pure forms. Stereochemical isomers and various synthetic intermediates are also synthesized and claimed for their novel compositions of matter. All compounds and their mixtures are claimed for use in formulations that are useful to treat or prevent cancer, or that have utility as selective estrogen receptor modulators, such formulations including enhanced or medical foods, dietary supplements and ethical pharmaceutical agents.

摘要翻译： 公开和要求的两种不同的方法用于合成甘氨酸蛋白I加血糖素II作为混合物，并以其纯形式。 立体化学异构体和各种合成中间体也由它们的新物质组合物合成和要求保护。 要求所有化合物及其混合物用于可用于治疗或预防癌症或具有选择性雌激素受体调节剂的制剂的制剂，所述制剂包括增强型或医用食品，膳食补充剂和伦理药剂。

公开(公告)号：WO2009111428A3

公开(公告)日：2009-12-10

申请号：PCT/US2009035803

申请日：2009-03-03

申请人： UNIV TULANE ,  UNIV TOLEDO ,  XAVIER UNIVERSITY OF LOUISIANA ,  US AGRICULTURE ,  ERHARDT PAUL W ,  KHUPSE RAHUL S ,  SARVER JEFFREY G ,  CLEVELAND THOMAS E ,  BOUE STEPHEN M ,  WIESE THOMAS E ,  BUROW MATTHEW E ,  MCLACHLAN JOHN A

发明人： ERHARDT PAUL W ,  KHUPSE RAHUL S ,  SARVER JEFFREY G ,  CLEVELAND THOMAS E ,  BOUE STEPHEN M ,  WIESE THOMAS E ,  BUROW MATTHEW E ,  MCLACHLAN JOHN A

IPC分类号： C07D493/02 ,  A61K31/353 ,  A61P5/24 ,  A61P35/00 ,  C07D311/04 ,  C07D311/74 ,  C07D493/14

CPC分类号： C07D493/14

摘要： Two distinct methods are disclosed and claimed for synthesizing glyceollin I plus glyceollin II as a mixture and as their pure forms. Stereochemical isomers and various synthetic intermediates are also synthesized and claimed for their novel compositions of matter. All compounds and their mixtures are claimed for use in formulations that are useful to treat or prevent cancer, or that have utility as selective estrogen receptor modulators, such formulations including enhanced or medical foods, dietary supplements and ethical pharmaceutical agents.

摘要翻译： 公开和要求的两种不同的方法用于合成甘氨酸蛋白I加血糖素II作为混合物，并以其纯形式。 立体化学异构体和各种合成中间体也由它们的新物质组合物合成和要求保护。 要求所有化合物及其混合物用于可用于治疗或预防癌症或具有选择性雌激素受体调节剂的制剂的制剂，所述制剂包括增强型或医用食品，膳食补充剂和伦理药剂。

公开(公告)号：WO2009026206A1

公开(公告)日：2009-02-26

申请号：PCT/US2008/073441

申请日：2008-08-18

申请人： UNIVERSITY OF TOLEDO ,  ERHARDT, Paul, W. ,  KHUPSE, Rahul, S.

发明人： ERHARDT, Paul, W. ,  KHUPSE, Rahul, S.

IPC分类号： C12C3/00

CPC分类号： C07C45/71 ,  C07C45/67 ,  C07C45/673 ,  C07C45/74 ,  Y02P20/55 ,  C07C49/84 ,  C07C47/575

摘要： A method is provided for synthesizing xanthohumol by inserting a prenyl-group onto the aryl-ring via a para-Claisen rearrangement after using a Mitsunobu reaction to establish the key prenylether precursor. A Claisen-Schmidt condensation is used to construct the chalcone scaffold followed by removal of MOM protecting groups under acidic conditions that are optimized to prevent concomitant cyclization to the flavone.

摘要翻译： 提供了一种用于通过在使用Mitsunobu反应建立关键的前乙烯基前体之后通过对Claisen重排将异戊烯基插入到芳基环上来合成黄腐酚的方法。 使用Claisen-Schmidt缩合物构建查耳酮支架，然后在酸性条件下除去MOM保护基团，其被优化以防止伴随的环化成黄酮。

公开(公告)号：WO2004080412A3

公开(公告)日：2005-05-26

申请号：PCT/US2004007269

申请日：2004-03-05

申请人： UNIV TOLEDO ,  ERHARDT PAUL W ,  KLIS WEISLAW A ,  SARVER JEFFREY G

发明人： ERHARDT PAUL W ,  KLIS WEISLAW A ,  SARVER JEFFREY G

IPC分类号： A01N37/18 ,  A61K20060101 ,  A61K38/00 ,  C07K2/00

CPC分类号： A61K31/337 ,  A61K38/06 ,  A61K38/07 ,  A61K38/08 ,  A61K47/54 ,  A61K47/543 ,  A61K47/55 ,  A61K47/551 ,  A61K47/554 ,  A61K47/64

摘要： Methods and compositions for treating cancer patients that include administering at least one or more hybrid derivatives of paclitaxel that simultaneously display improved aqueous solubility, chemical stability under physiological conditions, a decreased liability toward multi-drug resistance, and in certain instances enhanced selective toxicity toward cancer cells compared to normal cells. The derivative, paclitaxel substituted with at least one or more polar appendages at either the 7- or 10- positions as defined by a formula "7-OR-10-OR'-paclitaxel", is either deployed alone or in 10 combination protocols with other chemotherapeutic agents.

摘要翻译： 用于治疗癌症患者的方法和组合物包括给予紫杉醇的至少一种或多种杂合衍生物，其同时显示改善的水溶性，生理条件下的化学稳定性，对多药耐药性的降低的责任，并且在某些情况下增强对癌症的选择性毒性 细胞与正常细胞相比。 在由式“7-OR-10-OR” - 紫杉醇“定义的7位或10位上用至少一种或多种极性附属物取代的衍生物紫杉醇或者单独部署或以10种组合方案 其他化疗剂。

公开(公告)号：WO03030815A2

公开(公告)日：2003-04-17

申请号：PCT/US0230727

申请日：2002-09-27

申请人： UNIV TOLEDO ,  ERHARDT PAUL W ,  KLIS WEISLAW A ,  SARVER JEFFREY G

发明人： ERHARDT PAUL W ,  KLIS WEISLAW A ,  SARVER JEFFREY G

IPC分类号： C07D305/14 ,  A61K

CPC分类号： C07D305/14

摘要： A method for removing acyl-groups appended by an ester linkage to the 2'-hydroxyl group present in paclitaxel-related molecules comprising treatment with alcohol under non-acidic conditions. 2',7-bis-Monochloroacetylpaclitaxel analogs are converted to their corresponding 7-monochloroacetyl derivatives by treatment with alcohol under non-acidic conditions.

摘要翻译： 通过酯键除去附着在紫杉醇相关分子中的2'-羟基的酰基的方法，包括在非酸性条件下用醇处理。 2'，7-双 - 一氯乙酰基紫杉醇类似物通过在非酸性条件下用醇处理转化成其相应的7-一氯乙酰基衍生物。