Title:
HALOGEN-SUBSTITUTED PHENYLATE COMPOUND AND APPLICATIONS THEREOF
Document Type and Number:
WIPO Patent Application WO/2021/032161
Kind Code:
A1
Abstract:
Disclosed in the present invention are a halogen-substituted phenylate compound and applications thereof. Particularly provided are a compound shown in formula (I) or an optical isomer thereof, and pharmaceutically acceptable salts, prodrugs, aquo-complexes or non-aqueous-solvent complexes thereof. Experiments prove that, compared with a control compound MGL-3196, the compound shown in formula (I), which is obtained through specific substitution sites and specific substitution types in the present invention, is higher in agonist activity to THR-beta and significantly improved in selectivity on THR-beta/THR-alpha. Besides, the compound in the present invention is significantly enhanced in pharmacokinetic properties. The compound in the present invention has a good application prospect in preparing THR-beta agonist and drugs for treating adaption diseases (including dyslipidemia, hypercholesteremia, non-alcoholic steatohepatitis and non-alcoholic fatty liver disease) applicable to the THR-beta agonist.
Inventors:
DU WU (CN)
LI YU (CN)
LI HAIBO (CN)
CHEN YUANWEI (CN)
ZHANG CHENGZHI (CN)
LI XINGHAI (CN)
LI YU (CN)
LI HAIBO (CN)
CHEN YUANWEI (CN)
ZHANG CHENGZHI (CN)
LI XINGHAI (CN)
Application Number:
PCT/CN2020/110252
Publication Date:
February 25, 2021
Filing Date:
August 20, 2020
Export Citation:
Assignee:
HINOVA PHARMACEUTICALS INC (CN)
International Classes:
C07D403/12; A61K31/501; A61K31/53; A61P1/16; A61P3/04; A61P3/06; A61P3/10; A61P5/16; A61P9/10; C07D237/14; C07D237/16; C07D237/18; C07D403/02; C07D403/10
Domestic Patent References:
| WO2020169069A1 | 2020-08-27 | |||
| WO2020073974A1 | 2020-04-16 | |||
| WO2019240938A1 | 2019-12-19 |
Foreign References:
| CN110627773A | 2019-12-31 | |||
| CN111484481A | 2020-08-04 | |||
| CN109574995A | 2019-04-05 | |||
| CN101228135A | 2008-07-23 |
Other References:
MARTHA J KELLY; SHERRIE PIETRANICO-COLE; DOUGLAS LARIGAN J; NANCY-ELLEN HAYNES; CHARLES H REYNOLDS; NATHAN SCOTT; JOHN VERMEULEN; : "Discovery of 2‑[3，5-Dichloro-4-(5-isopropyl-6-oxo-1，6-dihydropyridazin-3-yloxy)phenyl]-3，5-dioxo-2，3，4，5-tetrahydro[1，2，4]triazine-6-carbonitrile (MGL-3196)， a Highly Selective Thyroid Hormone Receptor β Agonist in Clinical Trials for the Treatment of Dyslipidemia", JOURNAL OF MEDICINAL CHEMISTRY, vol. 57, no. 10, 22 May 2014 (2014-05-22), pages 3912 - 3923, XP055436939, ISSN: 0022-2623, DOI: 10.1021/jm4019299
SCOTT L. HARBECONROGER D. TUNG, DEUTERIUM IN DRUG DISCOVERY AND DEVELOPMENT, pages 405 - 406
CANADIAN JOURNAL OF CHEMISTRY, vol. 92, 2014, pages 305
J. MED. CHEM., vol. 57, 2014, pages 3912
See also references of EP 4019510A4
SCOTT L. HARBECONROGER D. TUNG, DEUTERIUM IN DRUG DISCOVERY AND DEVELOPMENT, pages 405 - 406
CANADIAN JOURNAL OF CHEMISTRY, vol. 92, 2014, pages 305
J. MED. CHEM., vol. 57, 2014, pages 3912
See also references of EP 4019510A4
Attorney, Agent or Firm:
GAOYUNG INTELLECTUAL PROPERTY AGENCY (GENERAL PARTNERSHIP) (CN)
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