Title:
SIDE-CHAIN MODIFIED ERGOSTEROL AND STIGMASTEROL DERIVATIVES AS LIVER X RECEPTOR MODULATORS
Document Type and Number:
WIPO Patent Application WO/2019/021122
Kind Code:
A3
Abstract:
The present invention relates to novel Liver X Receptor (LXR) modulators, their use in diagnostic and therapy, more particularly in the treatment of diseases associated with LXR, such as cancer, inflammation, metabolic and autoimmune diseases.
Inventors:
RUSSO VINCENZO (IT)
MARINOZZI MAURA (IT)
CASTRO NAVAS FRANCISCO FERMIN (ES)
MARINOZZI MAURA (IT)
CASTRO NAVAS FRANCISCO FERMIN (ES)
Application Number:
PCT/IB2018/055372
Publication Date:
March 07, 2019
Filing Date:
July 19, 2018
Export Citation:
Assignee:
OSPEDALE SAN RAFFAELE SRL (IT)
International Classes:
C07J9/00; A61K31/575; A61K31/58; A61P35/00; C07J17/00; C07J53/00; C07J71/00
Other References:
YU FLEGENTOV G ET AL: "22,23-Epoxides of Sitosterol and Related 7-Oxygenated [Delta]5-Sterols", RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY, KLUWER ACADEMIC PUBLISHERS-PLENUM PUBLISHERS, NE, vol. 31, no. 5, 1 September 2005 (2005-09-01), pages 475 - 481, XP019299976, ISSN: 1573-9163
KANEKO E ET AL: "INDUCTION OF INTESTINAL ATP-BINDING CASSETTE TRANSPORTERS BY A PHYTOSTEROL-DERIVED LIVER X RECEPTOR AGONIST", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, US, vol. 278, no. 38, 1 January 2003 (2003-01-01), pages 36091 - 36098, XP001199518, ISSN: 0021-9258, DOI: 10.1074/JBC.M304153200
MISHARIN ET AL: "Synthesis and cytotoxicity evaluation of 22,23-oxygenated stigmastane derivatives", BIOORGANIC & MEDICINAL CHEMISTRY, PERGAMON, GB, vol. 16, no. 3, 22 October 2007 (2007-10-22), pages 1460 - 1473, XP022453115, ISSN: 0968-0896, DOI: 10.1016/J.BMC.2007.10.056
KEN-ICHI MORITA ET AL: "Syntheses of 23-Ketositosterol and Its Derivatives", BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, vol. 36, no. 10, 1 October 1963 (1963-10-01), JP, pages 1332 - 1337, XP055512640, ISSN: 0009-2673, DOI: 10.1246/bcsj.36.1332
NIGEL BOSWORTH ET AL: "Unsaturated steroids. Part 2. A novel route to anthrasteroids: X-ray crystal structure of 1(10 ? 6)abeo-cholesta-5,7,9-trien-3-yl p-bromobenzoate", JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 1, no. 8, 1 January 1977 (1977-01-01), pages 805 - 809, XP055512634, ISSN: 0300-922X, DOI: 10.1039/p19770000805
PATRICK KOCH ET AL: "Identification de stérols à chaîne latérale oxygénée dans une éponge de l'espèce Hyrtios", HELVETICA CHIMICA ACTA, vol. 66, no. 8, 14 December 1983 (1983-12-14), CH, pages 2431 - 2436, XP055512604, ISSN: 0018-019X, DOI: 10.1002/hlca.19830660806
MASAO TADA ET AL: "Synthesis of 22,23-epoxyvitamin D2(22,23-epoxyergocalciferol)", JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 1, 1 January 1979 (1979-01-01), pages 1858 - 1861, XP055512592, ISSN: 0300-922X, DOI: 10.1039/p19790001858
JOHN T. GROVES ET AL: "Regioselective oxidation catalysis in synthetic phospholipid vesicles. Membrane-spanning steroidal metalloporphyrins", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 111, no. 8, 1 April 1989 (1989-04-01), US, pages 2900 - 2909, XP055512368, ISSN: 0002-7863, DOI: 10.1021/ja00190a026
FUMIHIRO KONDO ET AL: "Facile retro-cycloaddition of adducts derived from steroidal 5,7-diene and 4-phenyl-1,2,4-triazoline-3,5-dione by diisobutylaluminium hydride", JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 1, vol. 1, no. 21, 1 January 1995 (1995-01-01), pages 2679 - 2680, XP055512361, ISSN: 0300-922X, DOI: 10.1039/p19950002679
MAURA MARINOZZI ET AL: "Side-Chain Modified Ergosterol and Stigmasterol Derivatives as Liver X Receptor Agonists", JOURNAL OF MEDICINAL CHEMISTRY, vol. 60, no. 15, 25 July 2017 (2017-07-25), pages 6548 - 6562, XP055511605, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.7b00091
KANEKO E ET AL: "INDUCTION OF INTESTINAL ATP-BINDING CASSETTE TRANSPORTERS BY A PHYTOSTEROL-DERIVED LIVER X RECEPTOR AGONIST", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, US, vol. 278, no. 38, 1 January 2003 (2003-01-01), pages 36091 - 36098, XP001199518, ISSN: 0021-9258, DOI: 10.1074/JBC.M304153200
MISHARIN ET AL: "Synthesis and cytotoxicity evaluation of 22,23-oxygenated stigmastane derivatives", BIOORGANIC & MEDICINAL CHEMISTRY, PERGAMON, GB, vol. 16, no. 3, 22 October 2007 (2007-10-22), pages 1460 - 1473, XP022453115, ISSN: 0968-0896, DOI: 10.1016/J.BMC.2007.10.056
KEN-ICHI MORITA ET AL: "Syntheses of 23-Ketositosterol and Its Derivatives", BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, vol. 36, no. 10, 1 October 1963 (1963-10-01), JP, pages 1332 - 1337, XP055512640, ISSN: 0009-2673, DOI: 10.1246/bcsj.36.1332
NIGEL BOSWORTH ET AL: "Unsaturated steroids. Part 2. A novel route to anthrasteroids: X-ray crystal structure of 1(10 ? 6)abeo-cholesta-5,7,9-trien-3-yl p-bromobenzoate", JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 1, no. 8, 1 January 1977 (1977-01-01), pages 805 - 809, XP055512634, ISSN: 0300-922X, DOI: 10.1039/p19770000805
PATRICK KOCH ET AL: "Identification de stérols à chaîne latérale oxygénée dans une éponge de l'espèce Hyrtios", HELVETICA CHIMICA ACTA, vol. 66, no. 8, 14 December 1983 (1983-12-14), CH, pages 2431 - 2436, XP055512604, ISSN: 0018-019X, DOI: 10.1002/hlca.19830660806
MASAO TADA ET AL: "Synthesis of 22,23-epoxyvitamin D2(22,23-epoxyergocalciferol)", JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 1, 1 January 1979 (1979-01-01), pages 1858 - 1861, XP055512592, ISSN: 0300-922X, DOI: 10.1039/p19790001858
JOHN T. GROVES ET AL: "Regioselective oxidation catalysis in synthetic phospholipid vesicles. Membrane-spanning steroidal metalloporphyrins", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 111, no. 8, 1 April 1989 (1989-04-01), US, pages 2900 - 2909, XP055512368, ISSN: 0002-7863, DOI: 10.1021/ja00190a026
FUMIHIRO KONDO ET AL: "Facile retro-cycloaddition of adducts derived from steroidal 5,7-diene and 4-phenyl-1,2,4-triazoline-3,5-dione by diisobutylaluminium hydride", JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 1, vol. 1, no. 21, 1 January 1995 (1995-01-01), pages 2679 - 2680, XP055512361, ISSN: 0300-922X, DOI: 10.1039/p19950002679
MAURA MARINOZZI ET AL: "Side-Chain Modified Ergosterol and Stigmasterol Derivatives as Liver X Receptor Agonists", JOURNAL OF MEDICINAL CHEMISTRY, vol. 60, no. 15, 25 July 2017 (2017-07-25), pages 6548 - 6562, XP055511605, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.7b00091
Attorney, Agent or Firm:
SANTORO, Tiziana et al. (IT)
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