公开(公告)号：US10398678B2

公开(公告)日：2019-09-03

申请号：US15899171

申请日：2018-02-19

申请人： Vanderbilt University ,  The Trustees of the University of Pennsylvania

发明人： Lawrence J. Marnett ,  Andy J. Liedtke ,  Trevor M. Penning ,  Adegoke O. Adeniji ,  Michael C. Byrns

IPC分类号： C07D209/04 ,  A61K31/404 ,  A61K31/405 ,  C07D209/26 ,  C07D209/08 ,  C07D209/70 ,  C07D231/56 ,  C07D471/04

摘要： Provided are compositions for inhibiting a biological activity of an aldo-keto reductase family 1, member C3 (AKR1C3) polypeptide. In some embodiments, the compositions are indomethacin derivatives that are AKR1C3-specific inhibitors. Also provided are methods for producing disclosed indomethacin derivatives that substantially lack cyclooxygenase inhibitory activity but that have AKR1C3 inhibitory activity, methods for inhibiting AKR1C3 polypeptide biological activities, and methods for treating prostate tumors in subjects.

公开(公告)号：US11738004B2

公开(公告)日：2023-08-29

申请号：US17236694

申请日：2021-04-21

申请人： Vanderbilt University ,  The Trustees of the University of Pennsylvania

发明人： Lawrence J. Marnett ,  Andy J. Liedtke ,  Trevor M. Penning ,  Adegoke O. Adeniji ,  Michael C. Byrns

IPC分类号： C07D471/04 ,  A61K31/405 ,  A61K31/404 ,  C07D209/26 ,  C07D209/08 ,  C07D209/70 ,  C07D231/56

CPC分类号： A61K31/404 ,  A61K31/405 ,  C07D209/08 ,  C07D209/26 ,  C07D209/70 ,  C07D231/56 ,  C07D471/04

摘要： Provided are compositions for inhibiting a biological activity of an aldo-keto reductase family 1, member C3 (AKR1C3) polypeptide. In some embodiments, the compositions are indomethacin derivatives that are AKR1C3-specific inhibitors. Also provided are methods for producing disclosed indomethacin derivatives that substantially lack cyclooxygenase inhibitory activity but that have AKR1C3 inhibitory activity, methods for inhibiting AKR1C3 polypeptide biological activities, and methods for treating prostate tumors in subjects.

公开(公告)号：US09346803B2

公开(公告)日：2016-05-24

申请号：US14352421

申请日：2012-10-17

申请人： Vanderbilt University ,  The Trustees of the University of Pennsylvania

发明人： Lawrence J. Marnett ,  Andy J. Liedtke ,  Trevor M. Penning ,  Adegoke O. Adeniji ,  Michael C. Byrns

IPC分类号： C07D209/04 ,  C07D209/08 ,  C07D231/56 ,  C07D471/04 ,  C07D209/26 ,  C07D209/70

CPC分类号： A61K31/404 ,  A61K31/405 ,  C07D209/08 ,  C07D209/26 ,  C07D209/70 ,  C07D231/56 ,  C07D471/04

摘要： Provided are compositions for inhibiting a biological activity of an aldoketo reductase family 1, member C3 (AKR1 C3) polypeptide. In some embodiments, the compositions are indomethacin derivatives that are AKR1 C3-specific inhibitors. Also provided are methods for producing disclosed indomethacin derivatives that substantially lack cyclooxygenase inhibitory activity but that have AKR1C3 inhibitory activity, methods for inhibiting AKR1C3 polypeptide biological activities, and methods for treating prostate tumors in subjects.

摘要翻译： 提供了抑制醛糖还原酶家族1，成员C3（AKR1 C3）多肽的生物学活性的组合物。 在一些实施方案中，组合物是作为AKR1 C3特异性抑制剂的吲哚美辛衍生物。 还提供了生产基本上缺乏环加氧酶抑制活性但具有AKR1C3抑制活性的公开的吲哚美辛衍生物的方法，用于抑制AKR1C3多肽生物活性的方法和用于治疗受试者中前列腺肿瘤的方法。

公开(公告)号：US20180271835A1

公开(公告)日：2018-09-27

申请号：US15899171

申请日：2018-02-19

申请人： Vanderbilt University ,  The Trustees of the University of Pennsylvania

发明人： Lawrence J. Marnett ,  Andy J. Liedtke ,  Trevor M. Penning ,  Adegoke O. Adeniji ,  Michael C. Byrns

IPC分类号： A61K31/404 ,  A61K31/405 ,  C07D471/04 ,  C07D231/56 ,  C07D209/70 ,  C07D209/08 ,  C07D209/26

CPC分类号： A61K31/404 ,  A61K31/405 ,  C07D209/08 ,  C07D209/26 ,  C07D209/70 ,  C07D231/56 ,  C07D471/04

摘要： Provided are compositions for inhibiting a biological activity of an aldo-keto reductase family 1, member C3 (AKR1C3) polypeptide. In some embodiments, the compositions are indomethacin derivatives that are AKR1C3-specific inhibitors. Also provided are methods for producing disclosed indomethacin derivatives that substantially lack cyclooxygenase inhibitory activity but that have AKR1C3 inhibitory activity, methods for inhibiting AKR1C3 polypeptide biological activities, and methods for treating prostate tumors in subjects.

公开(公告)号：US09895351B2

公开(公告)日：2018-02-20

申请号：US15132937

申请日：2016-04-19

申请人： Vanderbilt University ,  The Trustees of the University of Pennsylvania

发明人： Lawrence J. Marnett ,  Andy J. Liedtke ,  Trevor M. Penning ,  Adegoke O. Adeniji ,  Michael C. Byrns

IPC分类号： A61K31/404 ,  A61K31/405 ,  C07D209/04 ,  C07D209/26 ,  C07D209/08 ,  C07D209/70 ,  C07D231/56 ,  C07D471/04

CPC分类号： A61K31/404 ,  A61K31/405 ,  C07D209/08 ,  C07D209/26 ,  C07D209/70 ,  C07D231/56 ,  C07D471/04

摘要： Provided are compositions for inhibiting a biological activity of an aldo-keto reductase family 1, member C3 (AKR1C3) polypeptide. In some embodiments, the compositions are indomethacin derivatives that are AKR1C3-specific inhibitors. Also provided are methods for producing disclosed indomethacin derivatives that substantially lack cyclooxygenase inhibitory activity but that have AKR1C3 inhibitory activity, methods for inhibiting AKR1C3 polypeptide biological activities, and methods for treating prostate tumors in subjects.

公开(公告)号：US20160159731A1

公开(公告)日：2016-06-09

申请号：US14993742

申请日：2016-01-12

申请人： The Trustees of the University of Pennsylvania

发明人： Trevor M. Penning ,  Adegoke O. ADENIJI ,  Michael C. BURNS ,  Jeffrey WINKLER ,  Barry TWENTER

IPC分类号： C07C229/58 ,  A61K45/06 ,  A61K31/196

CPC分类号： C07C229/58 ,  A61K31/195 ,  A61K31/196 ,  A61K31/205 ,  A61K31/405 ,  A61K45/06 ,  C07C229/60 ,  A61K2300/00

摘要： The invention includes compositions comprising selective AKR1C3 inhibitors. The invention also includes compositions comprising bifunctional AKR1C3 inhibitors and selective androgen receptor modulators. The invention further includes methods of treatment using the compositions of the invention.

摘要翻译： 本发明包括包含选择性AKR1C3抑制剂的组合物。 本发明还包括包含双功能AKR1C3抑制剂和选择性雄激素受体调节剂的组合物。 本发明还包括使用本发明组合物的治疗方法。

公开(公告)号：US09271961B2

公开(公告)日：2016-03-01

申请号：US14050937

申请日：2013-10-10

申请人： THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA

发明人： Trevor M. Penning ,  Adegoke O. Adeniji ,  Michael C. Burns ,  Jeffrey Winkler ,  Barry Twenter

IPC分类号： A61K31/196 ,  C07C229/60 ,  A61P35/00 ,  A61K31/405 ,  A61K31/195 ,  A61K31/205 ,  A61K45/06 ,  C07C229/58

CPC分类号： C07C229/58 ,  A61K31/195 ,  A61K31/196 ,  A61K31/205 ,  A61K31/405 ,  A61K45/06 ,  C07C229/60 ,  A61K2300/00

摘要： The invention includes compositions comprising selective AKR1C3 inhibitors. The invention also includes compositions comprising bifunctional AKR1C3 inhibitors and selective androgen receptor modulators. The invention further includes methods of treatment using the compositions of the invention.

摘要翻译： 本发明包括含有选择性AKR1C3抑制剂的组合物。 本发明还包括包含双功能AKR1C3抑制剂和选择性雄激素受体调节剂的组合物。 本发明还包括使用本发明组合物的治疗方法。

公开(公告)号：US20140371261A1

公开(公告)日：2014-12-18

申请号：US14352421

申请日：2012-10-17

申请人： Vanderbilt University ,  The Trustees of the University of Pennsylvania

发明人： Lawrence J. Marnett ,  Andy J. Liedtke ,  Trevor M. Penning ,  Adegoke O. Adeniji ,  Michael C. Byrns

IPC分类号： C07D471/04 ,  C07D209/70 ,  C07D231/56 ,  C07D209/08

CPC分类号： A61K31/404 ,  A61K31/405 ,  C07D209/08 ,  C07D209/26 ,  C07D209/70 ,  C07D231/56 ,  C07D471/04

摘要： Provided are compositions for inhibiting a biological activity of an aldoketo reductase family 1, member C3 (AKR1 C3) polypeptide. In some embodiments, the compositions are indomethacin derivatives that are AKR1 C3-specific inhibitors. Also provided are methods for producing disclosed indomethacin derivatives that substantially lack cyclooxygenase inhibitory activity but that have AKR1C3 inhibitory activity, methods for inhibiting AKR1C3 polypeptide biological activities, and methods for treating prostate tumors in subjects.

摘要翻译： 提供了抑制醛糖还原酶家族1，成员C3（AKR1 C3）多肽的生物学活性的组合物。 在一些实施方案中，组合物是作为AKR1 C3特异性抑制剂的吲哚美辛衍生物。 还提供了生产基本上缺乏环加氧酶抑制活性但具有AKR1C3抑制活性的公开的吲哚美辛衍生物的方法，用于抑制AKR1C3多肽生物活性的方法和用于治疗受试者中前列腺肿瘤的方法。

公开(公告)号：US11459295B2

公开(公告)日：2022-10-04

申请号：US15769565

申请日：2016-10-21

申请人： THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA ,  VANDERBILT UNIVERSITY

发明人： Trevor M. Penning ,  Adegoke Adeniji ,  Lawrence J. Marnett

IPC分类号： A61K31/405 ,  A61K31/4166 ,  A61K31/506 ,  A61K31/52 ,  A61K31/573 ,  A61K45/06 ,  A61P35/00 ,  C07C57/40 ,  C07C311/51 ,  C07C317/44 ,  C07C323/62 ,  C07C59/64 ,  A61K31/192 ,  A61K31/131 ,  A61K31/16 ,  A61K31/337

摘要： The invention includes 2-β-naphthyl-acetic acid derivatives, which are selective AKR1C3 inhibitors. In certain embodiments, the compounds of the invention are (R)-naproxen analogs. The invention further includes methods of treating cancer, such as prostate cancer and/or castration-resistant prostate cancer, using at least one compound of the invention.

公开(公告)号：US20210251960A1

公开(公告)日：2021-08-19

申请号：US17236694

申请日：2021-04-21

申请人： Vanderbilt University ,  The Trustees of the University of Pennsylvania

发明人： Lawrence J. Marnett ,  Andy J. Liedtke ,  Trevor M. Penning ,  Adegoke O. Adeniji ,  Michael C. Byrns

IPC分类号： A61K31/404 ,  C07D209/26 ,  C07D209/08 ,  C07D209/70 ,  C07D231/56 ,  C07D471/04 ,  A61K31/405

摘要： Provided are compositions for inhibiting a biological activity of an aldo-keto reductase family 1, member C3 (AKR1C3) polypeptide. In some embodiments, the compositions are indomethacin derivatives that are AKR1C3-specific inhibitors. Also provided are methods for producing disclosed indomethacin derivatives that substantially lack cyclooxygenase inhibitory activity but that have AKR1C3 inhibitory activity, methods for inhibiting AKR1C3 polypeptide biological activities, and methods for treating prostate tumors in subjects.