公开(公告)号：US20230310400A9

公开(公告)日：2023-10-05

申请号：US17359857

申请日：2021-06-28

Applicant: Wisconsin Alumni Research Foundation

Inventor： Weiping Tang ,  Ka Yang ,  Hao Wu

IPC: A61K31/4439

CPC classification number: A61K31/4439 ,  C07D401/14

Abstract: Histone deacetylase (“HDAC”)-selective inhibitors covalently bonded to a linker covalently bonded to an E3 ubiquitin ligase ligand, and salts thereof; pharmaceutical compositions containing them; methods of using the composition to inhibit neoplastic cell growth in mammals, including humans.

公开(公告)号：US11045458B2

公开(公告)日：2021-06-29

申请号：US16517943

申请日：2019-07-22

Applicant: Wisconsin Alumni Research Foundation

Inventor： Weiping Tang ,  Ka Yang ,  Hao Wu

IPC: C07D401/14 ,  C07D417/12 ,  A61P35/00 ,  A61P35/02 ,  A61K31/4439

Abstract: Histone deacetylase (“HDAC”)-selective inhibitors covalently bonded to a linker covalently bonded to an E3 ubiquitin ligase ligand, and salts thereof; pharmaceutical compositions containing them; methods of using the composition to inhibit neoplastic cell growth in mammals, including humans.

公开(公告)号：US20200022966A1

公开(公告)日：2020-01-23

申请号：US16517943

申请日：2019-07-22

Applicant: Wisconsin Alumni Research Foundation

Inventor： Weiping Tang ,  Ka Yang ,  Hao Wu

IPC: A61K31/4439

Abstract: Histone deacetylase (“HDAC”)-selective inhibitors covalently bonded to a linker covalently bonded to an E3 ubiquitin ligase ligand, and salts thereof; pharmaceutical compositions containing them; methods of using the composition to inhibit neoplastic cell growth in mammals, including humans.

公开(公告)号：US20240261416A1

公开(公告)日：2024-08-08

申请号：US18426920

申请日：2024-01-30

Applicant: Wisconsin Alumni Research Foundation

Inventor： Weiping Tang ,  Haibo Xie ,  Yunxiang Wu ,  Junzhuo Liao ,  Chunrong Li ,  Ira Tandon ,  Hua Tang

IPC: A61K47/55 ,  C07D239/22 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14

CPC classification number: A61K47/55 ,  C07D239/22 ,  C07D401/12 ,  C07D403/12 ,  C07D403/14

Abstract: Provided herein are achiral cereblon (CRBN) ligands based on phenyl dihydrouracil that have optimal binding to CRBN without having chiral carbons. Also provided herein are the proteolysis targeting chimeras (PROTACs) comprising the CRBN ligands and a protein binder, pharmaceutical compositions containing the PROTACs, and methods of treating diseases using the PROTACs.

公开(公告)号：US20230000771A1

公开(公告)日：2023-01-05

申请号：US17840964

申请日：2022-06-15

Applicant: Wisconsin Alumni Research Foundation

Inventor： Seungpyo Hong ,  Allan Brasier ,  Weiping Tang

IPC: A61K9/107 ,  A61K47/10 ,  A61K47/34 ,  A61K47/69

Abstract: A self-assembled therapeutic dendron-micelle includes a first amphiphilic dendron-coil, a second amphiphilic dendron-coil, and optionally a third amphiphilic dendron-coil, and an encapsulated BRD4 ligand or BRD4 proteolysis targeting chimera. The first and optional third amphiphilic dendron-coils have a therapeutic peptide conjugated thereto. Also included are pharmaceutical compositions containing the dendron-micelles, methods of making the dendron-micelles, and therapeutic methods including administering the dendron-micelles to a subject in need thereof.

公开(公告)号：US20210322398A1

公开(公告)日：2021-10-21

申请号：US17359857

申请日：2021-06-28

Applicant: Wisconsin Alumni Research Foundation

Inventor： Weiping Tang ,  Ka Yang ,  Hao Wu

IPC: A61K31/4439

Abstract: Histone deacetylase (“HDAC”)-selective inhibitors covalently bonded to a linker covalently bonded to an E3 ubiquitin ligase ligand, and salts thereof; pharmaceutical compositions containing them; methods of using the composition to inhibit neoplastic cell growth in mammals, including humans.

公开(公告)号：US20180222861A1

公开(公告)日：2018-08-09

申请号：US15946066

申请日：2018-04-05

Applicant: Wisconsin Alumni Research Foundation

Inventor： Weiping Tang ,  Xiaoxun Li ,  Dongxu Shu ,  Gabrielle N. Winston-McPherson

IPC: C07D209/14 ,  C07D405/14 ,  C07D403/06

CPC classification number: C07D209/14 ,  C07D209/12 ,  C07D403/06 ,  C07D405/14

Abstract: Described is a method to make diindolylmethanes and indolyl/pyrrolylmethanes, The method includes the steps of contacting an ether comprising an arylpropargyl moiety and an amine-protected, substituted or unsubstituted aniline moiety with a substituted or unsubstituted indol or a substituted or unsubstituted pyrrole, in the presence of a metal-containing catalyst, for a time and at a temperature to cause an annulation/arylation cascade reaction that yields a diindolylmethane or a indolyl/pyrrolylmethane. The resulting compounds are effective to modulate activity of arylhydrocarbon receptors, to inhibit activity of PCSK9, and to stimulate secretion of glucagon-like peptide 1 in mammals.

公开(公告)号：US20230064249A1

公开(公告)日：2023-03-02

申请号：US17782577

申请日：2020-12-04

Applicant: Wisconsin Alumni Research Foundation

Inventor： John Matthew Denu ,  Weiping Tang

IPC: A61K31/4035 ,  C07D209/48

Abstract: The present disclosure provides compounds according to Formula I and pharmaceutically acceptable salts thereof, as well as compositions including such compounds and a pharmaceutically acceptable carrier or excipient. Further provided are methods of inactivating SIRT6 with compounds of Formula I as well as compounds of Formula III, W2—R2—Y—R3, as described herein. In addition, the present technology provides methods of treatment using such compounds to lower LDL levels, lower triglyceride levels, and/or increase glucose tolerance in a subject, and/or to inhibit proliferation of ovarian, colorectal, hepatocellular, non-small cell lung, glioblastoma, osteosarcoma, pancreatic, and skin cancer cells, and/or inhibit liver and/or kidney fibrosis, and/or promote corneal epithelial wound healing.

公开(公告)号：US11427569B2

公开(公告)日：2022-08-30

申请号：US16789887

申请日：2020-02-13

Applicant: Wisconsin Alumni Research Foundation

Inventor： Weiping Tang ,  Gabrielle N. Winston-McPherson ,  Haibo Xie ,  Alan D. Attie ,  Mark Patrick Keller ,  Ka Yang

IPC: C07D403/06 ,  C07D401/14 ,  C07D409/06 ,  C07D413/14

Abstract: Described are benzoimidazole indolyl methane compounds, pharmaceutical compositions containing them, and use of the compounds to inhibit PCSK9-mediated ailments. The compounds have the structure:

公开(公告)号：US10730833B2

公开(公告)日：2020-08-04

申请号：US15946066

申请日：2018-04-05

Applicant: Wisconsin Alumni Research Foundation

Inventor： Weiping Tang ,  Xiaoxun Li ,  Dongxu Shu ,  Gabrielle N. Winston-McPherson

IPC: C07D209/14 ,  C07D403/06 ,  C07D405/14 ,  C07D209/12

Abstract: Described is a method to make diindolylmethanes and indolyl/pyrrolylmethanes, The method includes the steps of contacting an ether comprising an arylpropargyl moiety and an amine-protected, substituted or unsubstituted aniline moiety with a substituted or unsubstituted indol or a substituted or unsubstituted pyrrole, in the presence of a metal-containing catalyst, for a time and at a temperature to cause an annulation/arylation cascade reaction that yields a diindolylmethane or a indolyl/pyrrolylmethane. The resulting compounds are effective to modulate activity of arylhydrocarbon receptors, to inhibit activity of PCSK9, and to stimulate secretion of glucagon-like peptide 1 in mammals.