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Title:
SOS1 DEGRADING AGENT AND PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2022/223033
Kind Code:
A1
Abstract:
An SOS1 degrading agent and a preparation method therefor and an application thereof. Specifically, disclosed is a compound represented by formula I: S-L-E(I), wherein L is a linker chain, which connects S and E by means of covalent bonds; E is the small molecule ligand of an E3 ubiquitin ligase complex. The compound represented by formula I is capable of degrading and/or inhibiting an SOS1 protein in cells, and can be used to treat and/or prevent related diseases or disorders mediated by SOS1, or caused by an interaction between SOS1 and Ras or between SOS1 and Rac.

Inventors:
YE ZHENGQING (CN)
FENG YAN (CN)
LI SHIQIANG (CN)
DING CHENLI (CN)
WANG QIAO (CN)
WEI HONG (CN)
XIE SHUCHEN (CN)
Application Number:
PCT/CN2022/088560
Publication Date:
October 27, 2022
Filing Date:
April 22, 2022
Export Citation:
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Assignee:
SHANGHAI LEADINGTAC PHARMACEUTICAL CO LTD (CN)
International Classes:
C07D239/94; A61K31/517; A61P35/00; C07D401/14
Domestic Patent References:
WO2022061348A12022-03-24
WO2018115380A12018-06-28
WO2019140380A12019-07-18
WO2018172250A12018-09-27
WO2018172250A12018-09-27
WO2020173935A12020-09-03
WO2019201848A12019-10-24
WO2020180768A12020-09-10
WO2020180770A12020-09-10
WO2019122129A12019-06-27
WO2018115380A12018-06-28
WO2017007612A12017-01-12
WO2017161119A12017-09-21
WO2018237026A12018-12-27
WO2017176958A12017-10-12
WO2010066868A22010-06-17
Foreign References:
CN112218859A2021-01-12
EP3558979A12019-10-30
US20180134684A12018-05-17
US20160272639A12016-09-22
CN108601764A2018-09-28
Other References:
ZHOU CHUAN, FAN ZISHENG, ZHOU ZEHUI, LI YUPENG, CUI RONGRONG, LIU CHAOYI, ZHOU GUIZHEN, DIAO XINGXING, JIANG HUALIANG, ZHENG MINGY: "Discovery of the First-in-Class Agonist-Based SOS1 PROTACs Effective in Human Cancer Cells Harboring Various KRAS Mutations", JOURNAL OF MEDICINAL CHEMISTRY, vol. 65, no. 5, 10 March 2022 (2022-03-10), US , pages 3923 - 3942, XP055978386, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.1c01774
HILLIG ROMAN C; SAUTIER BRICE; SCHROEDER JENS; MOOSMAYER DIETER; HILPMANN ANDRÉ; STEGMANN CHRISTIAN M; WERBECK NICOLAS D; BRIEM HA: "Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, vol. 116, no. 7, 12 February 2019 (2019-02-12), pages 2551 - 2560, XP055841142, ISSN: 0027-8424, DOI: 10.1073/pnas.1812963116
RAMHARTER JUERGEN, KESSLER DIRK, ETTMAYER PETER, HOFMANN MARCO H., GERSTBERGER THOMAS, GMACHL MICHAEL, WUNBERG TOBIAS, KOFINK CHRI: "One Atom Makes All the Difference: Getting a Foot in the Door between SOS1 and KRAS", JOURNAL OF MEDICINAL CHEMISTRY, vol. 64, no. 10, 27 May 2021 (2021-05-27), US , pages 6569 - 6580, XP055978399, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.0c01949
Attorney, Agent or Firm:
SHANGHAI BESHINING LAW OFFICE (CN)
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