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Title:
METHOD OF TREATING SHIP1-MEDIATED DISEASES USING PELOROL DERIVATIVES
Document Type and Number:
WIPO Patent Application WO/2021/213393
Kind Code:
A1
Abstract:
Provided are compounds of Formula I and pharmaceutically acceptable salt, solvate and/or derivative thereof. Further, provided are methods of treating a disease, disorder or condition mediated or treatable by activation of SHIP1 comprising administering a compound of Formula I or a pharmaceutically acceptable salt, solvate or derivative thereof. The compound of Formula I or a pharmaceutically acceptable salt, solvate or derivative thereof may be used in the treatment of SHIP1 mediated disease, disorder or conditions including inflammatory bowel disease (IBD), Crohn' disease, ulcerative colitis, multiple myeloma, liver injury, acute hepatitis and severe sepsis.

Inventors:
WEN XIAO-YAN (CA)
ANDERSEN RAYMOND JOHN (CA)
MUI ALICE LOW-FUNG (CA)
ZHAO YUANYUAN (CN)
Application Number:
PCT/CN2021/088448
Publication Date:
October 28, 2021
Filing Date:
April 20, 2021
Export Citation:
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Assignee:
ZEBRAPEUTICS INC (CA)
International Classes:
C07J69/00; A61K31/56; A61P1/16; A61P9/00; A61P11/06; A61P19/10; A61P27/14; A61P29/00; A61P35/00; A61P35/02; A61P37/06; A61P37/08
Domestic Patent References:
WO2007147251A12007-12-27
WO2012024682A12012-02-23
WO2004035601A12004-04-29
Other References:
CHAMBERLAIN,T.C. ET AL.: "Interleukin-10 and Small Molecule SHIP1 Allosteric Regulators Trigger Anti-inflammatory Effects through SHIP1/STAT3 Complexes.", ISCIENCE., vol. 23, no. 8, 21 August 2020 (2020-08-21), pages 1 - 31, XP055860320, ISSN: 2589-0042
NODWELL,M.B.: "Synthesis of Biologically Active Marine Natural Product Analogues", SELECTED ORGANIC REACTIONS DATABASE (SORD), January 2009 (2009-01-01), pages i-ii,46,55 - 56, XP009532119
YANG LU, ET AL: "Synthesis of pelorol and analogues: Activators of the inositol 5-phosphatase SHIP", ORGANIC LETTERS, vol. 7, no. 6, 17 March 2005 (2005-03-17), US , pages 1073 - 1076, XP002563127, ISSN: 1523-7060, DOI: 10.1021/ol047316m
LABROS G. MEIMETIS, MATT NODWELL, LU YANG, XIAOXIA WANG, JOYCE WU, CURTIS HARWIG, GRANT R. STENTON, LLOYD F. MACKENZIE, THOMAS MAC: "Synthesis of SHIP1-Activating Analogs of the Sponge Meroterpenoid Pelorol", EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, vol. 2012, no. 27, 1 September 2012 (2012-09-01), DE , pages 5195 - 5207, XP055548711, ISSN: 1434-193X, DOI: 10.1002/ejoc.201200631
ONG CHRISTOPHER J, ET AL: "Small-molecule agonists of SHEP1 inhibit the phosphoinositide 3-kinase pathway in hematopoietic cells", BLOOD, vol. 110, no. 6, 15 September 2007 (2007-09-15), US , pages 1942 - 1949, XP002563126, ISSN: 0006-4971, DOI: 10.1182/blood-2007-03-079699
KENNAH, M. ; YAU, T.Y. ; NODWELL, M. ; KRYSTAL, G. ; ANDERSEN, R.J. ; ONG, C.J. ; MUI, A.L.F.: "Activation of SHIP via a small molecule agonist kills multiple myeloma cells", EXPERIMENTAL HEMATALOGY, vol. 37, no. 11, 1 November 2009 (2009-11-01), US , pages 1274 - 1283, XP026691941, ISSN: 0301-472X, DOI: 10.1016/j.exphem.2009.08.001
LIERMANN JOHANNES C., KOLSHORN HEINZ, ANKE HEIDRUN, THINES ECKHARD, OPATZ TILL: "Tetracyclic Terpenoids from Dasyscyphus niveus , Dasyscyphins D and E", JOURNAL OF NATURAL PRODUCTS, vol. 71, no. 9, 1 September 2008 (2008-09-01), US , pages 1654 - 1656, XP055860335, ISSN: 0163-3864, DOI: 10.1021/np800355a
See also references of EP 4143202A4
Attorney, Agent or Firm:
IP MARCH (CN)
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