Title:
GUAIANE SESQUITERPENE DERIVATIVES AND PHARMACEUTICAL USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2022/247909
Kind Code:
A1
Abstract:
Disclosed are a class of guaiane sesquiterpene derivatives and the pharmaceutical use thereof. The guaiane sesquiterpene derivative or a pharmaceutically acceptable salt thereof is as represented by general formula I. A class of new guaiane sesquiterpene derivatives having a strong inhibitory activity against NLPR3 inflammasome activation and having significantly improved chemical stability, water solubility and oral bioavailability are discovered from abundant natural ingredients such as parthenolide and dehydrocostus lactone as raw materials by means of structural optimization, and experiments prove that the derivatives have the effect of inhibiting the activity of NLRP3 inflammasomes, and have potential pharmaceutical applications.
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Inventors:
HU LIHONG (CN)
LIU JIAN (CN)
LV QI (CN)
HU YANG (CN)
DONG DONG (CN)
WANG PING (CN)
YANG MENG (CN)
LIU JIAN (CN)
LV QI (CN)
HU YANG (CN)
DONG DONG (CN)
WANG PING (CN)
YANG MENG (CN)
Application Number:
PCT/CN2022/095243
Publication Date:
December 01, 2022
Filing Date:
May 26, 2022
Export Citation:
Assignee:
UNIV NANJING CHINESE MEDICINE (CN)
International Classes:
C07D307/93; A61K31/365; A61K31/495; A61K31/496; A61K31/5377; A61P29/00; C07D405/06; C07D407/06
Foreign References:
| CN103622954A | 2014-03-12 | |||
| CN103417532A | 2013-12-04 | |||
| CN102731454A | 2012-10-17 | |||
| US20200277270A1 | 2020-09-03 |
Other References:
DING YA-HUI; GAO XUE; LONG JING; KUANG BEI-JIA; CHEN YUE; ZHANG QUAN: "Dispirocyclopropyldehydrocostus lactone selectively inhibits acute myelogenous leukemia cells", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 26, no. 4, 18 January 2016 (2016-01-18), Amsterdam NL , pages 1165 - 1168, XP029409782, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2016.01.046
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CELL METAB, vol. 31, 2020, pages 580 - 591
CIRC RES, vol. 122, 2018, pages 1722 - 1740
J HEPATOL, vol. 66, 2017, pages 1037 - 1046
AGEING RES REV, vol. 64, 2020, pages 101192
AUTOPHAGY, vol. 15, 2019, pages 1860 - 1881
BRAIN, vol. 143, 2020, pages 1414 - 1430
MUCOSAL IMMUNOL, vol. 12, 2019, pages 1150 - 1163
J CLIN INVEST, vol. 128, 2018, pages 1793 - 1806
IMMUNOLOGY, vol. 160, 2020, pages 78 - 89
J INFLAMM (LOND, vol. 12, 2015, pages 41
NAT COMMUN, vol. 11, 2020, pages 4243
FRONT IMMUNOL, vol. 11, 2020, pages 570251
BIOCHEMBIOPHYS RES COMMUN, vol. 477, 2016, pages 329 - 335
PHARMACEUTICS, vol. 12, 2020, pages 867
ARTHRITIS RHEUMATOL, vol. 72, 2020, pages 1192 - 1202
FOOD CHEM TOXICOL, vol. 144, 2020, pages 111588
EMBO REP, vol. 21, 2020, pages e49666
INT IMMUNOPHARMACOL, vol. 81, 2020, pages 106257
CELLS, vol. 8, 2019, pages 1389
CELL PROLIF, vol. 54, 2021, pages e12973
CIRCULATION, vol. 131, 2015, pages 1061 - 1070
J PHARMACOL EXP THER, vol. 357, 2016, pages 487 - 494
J NAT PROP, vol. 62, 1999, pages 1068 - 1071
SALAZAR, I. ; DIAZ, E.: "Carbofluorination of pseudoguaianolide sesquiterpenic lactones", TETRAHEDRON, ELSEVIER SIENCE PUBLISHERS,, vol. 35, no. 7, 1 January 1979 (1979-01-01), AMSTERDAM, NL , pages 815 - 818, XP026658825, ISSN: 0040-4020, DOI: 10.1016/0040-4020(79)80099-X
CELL, vol. 165, 2016, pages 792 - 800
NAT REV DRUG DISCOV, vol. 17, 2018, pages 588 - 606
IMMUNOL REV, vol. 265, 2015, pages 35 - 52
NAT MED, vol. 21, 2015, pages 248 - 255
J CLIN INVEST, vol. 130, 2020, pages 1961 - 1976
CELL METAB, vol. 31, 2020, pages 580 - 591
CIRC RES, vol. 122, 2018, pages 1722 - 1740
J HEPATOL, vol. 66, 2017, pages 1037 - 1046
AGEING RES REV, vol. 64, 2020, pages 101192
AUTOPHAGY, vol. 15, 2019, pages 1860 - 1881
BRAIN, vol. 143, 2020, pages 1414 - 1430
MUCOSAL IMMUNOL, vol. 12, 2019, pages 1150 - 1163
J CLIN INVEST, vol. 128, 2018, pages 1793 - 1806
IMMUNOLOGY, vol. 160, 2020, pages 78 - 89
J INFLAMM (LOND, vol. 12, 2015, pages 41
NAT COMMUN, vol. 11, 2020, pages 4243
FRONT IMMUNOL, vol. 11, 2020, pages 570251
BIOCHEMBIOPHYS RES COMMUN, vol. 477, 2016, pages 329 - 335
PHARMACEUTICS, vol. 12, 2020, pages 867
ARTHRITIS RHEUMATOL, vol. 72, 2020, pages 1192 - 1202
FOOD CHEM TOXICOL, vol. 144, 2020, pages 111588
EMBO REP, vol. 21, 2020, pages e49666
INT IMMUNOPHARMACOL, vol. 81, 2020, pages 106257
CELLS, vol. 8, 2019, pages 1389
CELL PROLIF, vol. 54, 2021, pages e12973
CIRCULATION, vol. 131, 2015, pages 1061 - 1070
J PHARMACOL EXP THER, vol. 357, 2016, pages 487 - 494
J NAT PROP, vol. 62, 1999, pages 1068 - 1071
Attorney, Agent or Firm:
NANJING SUGAO PATENT AND TRADEMARK FIRM (ORDINARY PARTNERSHIP) (CN)
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