公开(公告)号：US20190185478A1

公开(公告)日：2019-06-20

申请号：US16226398

申请日：2018-12-19

Applicant: Agency for Science, Technology and Research

Inventor： Jenefer Alam ,  Soo Yei Ho ,  Wei Ling Wang ,  Athisayamani Jeyaraj Duraiswamy

IPC: C07D487/04

CPC classification number: C07D487/04

Abstract: The present invention relates to compounds of formula (I), combinations and uses thereof for disease therapy, or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof wherein R1 represents H; optionally substituted alkyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkoxy, NH2, —NHC1-3alkyl and —N(C1-3alkyl)2); —C(O)Oalkyl; haloalkyl; haloalkoxy; or -alkylaryl; each R2 independently represents H; optionally substituted alkyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkoxy, NH2, —NHC1-3alkyl and —N(C1-3alkyl)2); -alkylaryl; optionally substituted carbocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy and halo); optionally substituted heterocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, —C(O)OC1-6alkyl, —C(O)C1-6alkyl and —C(O)NHC1-6alkyl); —NHalkyl; —N(alkyl)2; amino; hydroxyl; alkoxy or halo; n represents 0, 1 or 2; R3 represents H or alkyl; R4 represents H or alkyl; R5 represents H or alkyl; W and X each independently represent C═O; C═S; or CH2; Y represents aryl; heteroaryl; optionally substituted carbocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy and halo); or optionally substituted heterocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, —C(O)OC1-6alkyl, —C(O)C1-6alkyl and —C(O)NHC1-6alkyl); and Z represents optionally substituted alkyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkoxy, NH2, —NHC1-3alkyl and —N(C1-3alkyl)2); aryl; heteroaryl; -alkylaryl;-alkylheteroaryl; optionally substituted carbocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy and halo); optionally substituted heterocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, —C(O)OC1-6alkyl, —C(O)C1-6alkyl and —C(O)NHC1-6alkyl); -alkylcarbocyclyl wherein carbocyclyl is optionally substituted (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkoxy and halo); -alkylheterocyclyl wherein heterocyclyl is optionally substituted (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, —C(O)OC1-6alkyl, —C(O)C1-6alkyl and —C(O)NHC1-6alkyl); -arylcarbocyclyl wherein carbocyclyl is optionally substituted (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkoxy and halo); or -arylheterocyclyl wherein heterocyclyl is optionally substituted (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, —C(O)OC1-6alkyl, —C(O)C1-6alkyl and —C(O)NHC1-6alkyl).

公开(公告)号：US20210147441A1

公开(公告)日：2021-05-20

申请号：US17028574

申请日：2020-09-22

Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH (A*STAR)

Inventor： Wei Hung ,  Thomas Hugo Keller ,  Wei Ling Wang ,  Gang Wang ,  Congbao Kang

IPC: C07D495/14 ,  C07D519/00

Abstract: There are provided new heterobifuctional agents designed to mediated formation of protein-protein dimers and promote ubiqutination of a protein of the dimer. Also provided are methods of synthesizing the agents, pharmaceutical formulations including the agents, and methods of using the agents to treat, ameliorate or cure diseases characterized by protein over-expression or malfunction.

公开(公告)号：US20210047336A1

公开(公告)日：2021-02-18

申请号：US17084507

申请日：2020-10-29

Applicant: Agency for Science, Technology and Research

Inventor： Jenefer Alam ,  Soo Yei Ho ,  Wei Ling Wang ,  Athisayamani Jeyaraj Duraiswamy

IPC: C07D487/04 ,  A61K31/519 ,  A61P35/04 ,  A61P35/00

Abstract: The present invention relates to compounds of formula (I), combinations and uses thereof for disease therapy, or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof wherein R1 represents H; optionally substituted alkyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkoxy, NH2, —NHC1-3alkyl and —N(C1-3alkyl)2); —C(O)Oalkyl; haloalkyl; haloalkoxy; or -alkylaryl; each R2 independently represents H; optionally substituted alkyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkoxy, NH2, —NHC1-3alkyl and —N(C1-3alkyl)2); -alkylaryl; optionally substituted carbocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy and halo); optionally substituted heterocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, —C(O)OC1-6alkyl, —C(O)C1-6alkyl and —C(O)NHC1-6alkyl); —NHalkyl; —N(alkyl)2; amino; hydroxyl; alkoxy or halo; n represents 0, 1 or 2; R3 represents H or alkyl; R4 represents H or alkyl; R5 represents H or alkyl; W and X each independently represent C═O; C═S; or CH2; Y represents aryl; heteroaryl; optionally substituted carbocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy and halo); or optionally substituted heterocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, —C(O)OC1-6alkyl, —C(O)C1-6alkyl and —C(O)NHC1-6alkyl); and Z represents optionally substituted alkyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkoxy, NH2, —NHC1-3alkyl and —N(C1-3alkyl)2); aryl; heteroaryl; -alkylaryl; -alkylheteroaryl; optionally substituted carbocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy and halo); optionally substituted heterocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, —C(O)OC1-6alkyl, —C(O)C1-6alkyl and —C(O)NHC1-6alkyl); -alkylcarbocyclyl wherein carbocyclyl is optionally substituted (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkoxy and halo); -alkylheterocyclyl wherein heterocyclyl is optionally substituted (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, —C(O)OC1-6alkyl, —C(O)C1-6alkyl and —C(O)NHC1-6alkyl); -arylcarbocyclyl wherein carbocyclyl is optionally substituted (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkoxy and halo); or -arylheterocyclyl wherein heterocyclyl is optionally substituted (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, —C(O)OC1-6alkyl, —C(O)C1-6alkyl and —C(O)NHC1-6alkyl).

公开(公告)号：US11542274B1

公开(公告)日：2023-01-03

申请号：US17483731

申请日：2021-09-23

Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH (A*STAR)

Inventor： Wei Hung ,  Thomas Hugo Keller ,  Wei Ling Wang ,  Gang Wang ,  Congbao Kang

IPC: C07D495/14 ,  C07D519/00

Abstract: There are provided new heterobifunctional agents designed to mediated formation of protein-protein dimers and promote ubiquitination of a protein of the dimer. Also provided are methods of synthesizing the agents, pharmaceutical formulations including the agents, and methods of using the agents to treat, ameliorate or cure diseases characterized by protein over-expression or malfunction.

公开(公告)号：US10189842B2

公开(公告)日：2019-01-29

申请号：US15105224

申请日：2014-12-17

Applicant: Agency for Science, Technology and Research

Inventor： Jenefer Alam ,  Soo Yei Ho ,  Wei Ling Wang ,  Athisayamani Jeyaraj Duraiswamy

IPC: C07D487/04 ,  A61K31/519 ,  A61P35/00 ,  A61P19/02 ,  A61P19/04 ,  A61P17/06 ,  A61P9/04

Abstract: The present invention relates to dihydropyrazolo[1,5-a]pyrimidine compounds of formula I, defined herein, as WNT pathways modulators, processes for making them, and pharmaceutical compositions comprising them. Methods of treatment of conditions mediated by WNT pathway signalling including cancer, fibrosis, stem cell and diabetic retinopathy, rheumatoid arthritis, psoriasis and myocardial infarction, comprising the compounds of formula I are also provided.

公开(公告)号：US11434245B2

公开(公告)日：2022-09-06

申请号：US17084507

申请日：2020-10-29

Applicant: Agency for Science, Technology and Research

Inventor： Jenefer Alam ,  Soo Yei Ho ,  Wei Ling Wang ,  Athisayamani Jeyaraj Duraiswamy

IPC: A61K31/519 ,  A61P19/04 ,  C07D487/04 ,  A61P35/04 ,  A61P35/00

Abstract: The present invention relates to compounds of formula (I), combinations and uses thereof for disease therapy, or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof wherein.

公开(公告)号：US09981964B2

公开(公告)日：2018-05-29

申请号：US15105312

申请日：2014-12-17

Applicant: Agency for Science, Technology and Research

Inventor： Jenefer Alam ,  Anders Poulsen ,  Soo Yei Ho ,  Wei Ling Wang ,  Athisayamani Jeyaraj Duraiswamy

IPC: C07D471/04 ,  C07D487/04

CPC classification number: C07D471/04 ,  C07D487/04

Abstract: The present invention relates to compounds of formula (I), combinations and uses thereof for disease therapy, or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof wherein R1 represents optionally substituted alkyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkoxy); optionally substituted carbocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy and halo); or -alkylaryl; R2 represents H; or alkyl; R3 represents H; or alkyl; U, V and W represent —(CH2)—; or U and V together represent —CH═CH— and W represents C═O; Y represents aryl; heteroaryl; optionally substituted carbocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy and halo); or optionally substituted heterocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6 alkoxy, —C(O)OC1-6alkyl, —C(O)C1-6alkyl and —C(O)NHC1-6alkyl); and Z represents aryl; heteroaryl; optionally substituted carbocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy and halo); or optionally substituted heterocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6 alkoxy, —C(O)OC1-6alkyl, —C(O)C1-6alkyl and —C(O)NHC1-6alkyl).

公开(公告)号：US20160318926A1

公开(公告)日：2016-11-03

申请号：US15105312

申请日：2014-12-17

Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

Inventor： Jenefer Alam ,  Anders Poulsen ,  Soo Yei Ho ,  Wei Ling Wang ,  Athisayamani Jeyaraj Duraiswamy

IPC: C07D471/04

CPC classification number: C07D471/04 ,  C07D487/04

Abstract: The present invention relates to compounds of formula (I), combinations and uses thereof for disease therapy, or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof wherein R1 represents optionally substituted alkyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkoxy); optionally substituted carbocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy and halo); or -alkylaryl; R2 represents H; or alkyl; R3 represents H; or alkyl; U, V and W represent —(CH2)—; or U and V together represent —CH═CH— and W represents C═O; Y represents aryl; heteroaryl; optionally substituted carbocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy and halo); or optionally substituted heterocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6 alkoxy, —C(O)OC1-6alkyl, —C(O)C1-6alkyl and —C(O)NHC1-6alkyl); and Z represents aryl; heteroaryl; optionally substituted carbocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy and halo); or optionally substituted heterocyclyl (wherein optional substituents include one or more substituents each independently selected from C1-6alkyl, C1-6 alkoxy, —C(O)OC1-6alkyl, —C(O)C1-6alkyl and —C(O)NHC1-6alkyl).

Abstract translation: 本发明涉及式（I）化合物，其用于疾病治疗的组合和用途，或其药学上可接受的盐，溶剂化物或多晶型物，包括所有互变异构体和立体异构体，其中R 1表示任选取代的烷基（其中任选的取代基包括一个或多个 取代基，各自独立地选自C 1-6烷氧基）; 任选取代的碳环基（其中任选的取代基包括一个或多个取代基，各自独立地选自C 1-6烷基，C 1-6烷氧基，C 1-6卤代烷基，C 1-6卤代烷氧基和卤素）; 或 - 烷基芳基; R2表示H; 或烷基; R3表示H; 或烷基; U，V和W表示 - （CH 2） - ; 或U和V一起表示-CH = CH-，W表示C = O; Y表示芳基; 杂芳基; 任选取代的碳环基（其中任选的取代基包括一个或多个各自独立地选自C 1-6烷基，C 1-6烷氧基，C 1-6卤代烷基，C 1-6卤代烷氧基和卤素的取代基）。 或任选取代的杂环基（其中任选的取代基包括一个或多个各自独立地选自C 1-6烷基，C 1-6烷氧基，-C（O）OC 1-6烷基，-C（O）C 1-6烷基和-C（O）NHCl -6-烷基）; Z表示芳基; 杂芳基; 任选取代的碳环基（其中任选的取代基包括一个或多个各自独立地选自C 1-6烷基，C 1-6烷氧基，C 1-6卤代烷基，C 1-6卤代烷氧基和卤素的取代基）。 或任选取代的杂环基（其中任选的取代基包括一个或多个各自独立地选自C 1-6烷基，C 1-6烷氧基，-C（O）OC 1-6烷基，-C（O）C 1-6烷基和-C（O） NHC 1-6烷基）。