Title:
AR AND BET DUAL INHIBITOR AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2020/063968
Kind Code:
A1
Abstract:
Provided are a polycyclic compound as shown in formula (I) and use thereof in an AR and BET dual inhibitor. Specifically, provided are a compound as shown in formula (I) or use of an optical isomer, a solvate, a pharmacologically acceptable salt, a prodrug, a tautomer, a mesomer, a racemate, an enantiomer, a diastereoisomer, a mixture form, a metabolite, a metabolic precursor, or an isotope substitution form thereof in preparation of the AR and BET dual inhibitor. Experimental results show that the compound can not only inhibit transcription of PSA and FKBP5 downstream of the AR, but also inhibit the transcriptional activity of anthracythramine-resistance AR-F876L mutants, and can lower the expression of protein c-Myc downstream of BRD4. Moreover, the compound has better binding affinity to AR and BET proteins, which indicates that the compound can simultaneously inhibit the activity of the AR and BET proteins and thus has good application prospect in preparation of drugs for preventing and/or treating diseases related to the BET protein.
Inventors:
YU JIANG (CN)
CHEN YUANWEI (CN)
CHEN YUANWEI (CN)
Application Number:
PCT/CN2019/109077
Publication Date:
April 02, 2020
Filing Date:
September 29, 2019
Export Citation:
Assignee:
UNIV SICHUAN (CN)
International Classes:
A61K31/42; A61K31/277; A61K31/351; A61K31/415; A61K31/4155; A61K31/4184; A61P35/00; C07D401/04
Domestic Patent References:
| WO2016087942A1 | 2016-06-09 | |||
| WO2016087942A1 | 2016-06-09 | |||
| WO2016087936A1 | 2016-06-09 |
Foreign References:
| CN107814785A | 2018-03-20 |
Other References:
YU, JIANG ET AL.: "Discovery and biological evaluation of novel androgen receptor antagonist for castration-resistant prostate cancer", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 171, 22 March 2019 (2019-03-22), pages 265 - 281, XP085661306, ISSN: 0223-5234, DOI: 20191219132759
ASANGANI, I. A. ET AL.: "BET Bromodomain Inhibitors Enhance Efficacy and Disrupt Resistance to AR Antagonists in the Treatment of Prostate Cancer", MOLECULAR CANCER RESEARCH, vol. 14, no. 4, 1 April 2017 (2017-04-01), pages 324 - 331, XP055442743, ISSN: 1541-7786, DOI: 20191219133149PX
ASANGANI, I. A. ET AL.: "BET Bromodomain Inhibitors Enhance Efficacy and Disrupt Resistance to AR Antagonists in the Treatment of Prostate Cancer", MOLECULAR CANCER RESEARCH, vol. 14, no. 4, 1 April 2017 (2017-04-01), pages 324 - 331, XP055442743, ISSN: 1541-7786, DOI: 20191219133149PX
Attorney, Agent or Firm:
GAOYUNG INTELLECTUAL PROPERTY AGENCY (GENERAL PARTNERSHIP) (CN)
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