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Title:
SELECTIVE INHIBITORS AND ALLOSTERIC ACTIVATORS OF SPHINGOSINE KINASE
Document Type and Number:
WIPO Patent Application WO/2014/118556
Kind Code:
A3
Abstract:
Sphingosine 1-phosphate (S1P) is involved in hyper-proliferative diseases, such as cancer and vascular remodeling in pulmonary arterial hypertension. Inhibitors of sphingosine kinase 1 and 2 (SK1 and SK2), which catalyze the synthesis of S1P, may be useful anti- proliferative agents. We have synthesized a series of sphingosine-based inhibitors of SK and SK2. Also provided in this invention are compounds that activate SK1 which can be used in diseases such as fibrosis, where intracellular S1P is anti-fibrotic.

Inventors:
BITTMAN, Robert (65-30 Kissena Blvd, Queens, New York, 11367-1597, US)
PYNE, Nigel J. (Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde161 Cathedral Street,Glasgow, G4 0RE, GB)
PYNE, Susan (Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde161 Cathedral Street,Glasgow, G4 0RE, GB)
BAEK, Dong Jae (194-60B 64th Ave #1A, Fresh Meadows, New York, 11365, US)
LIU, Zheng (1015 Essex street SE, #208Minneapolis, Minnesota, 55414, US)
BYUN, Hoe Sup (45-31 218th Street, Bayside, New York, 11361, US)
Application Number:
GB2014/050264
Publication Date:
September 25, 2014
Filing Date:
January 31, 2014
Export Citation:
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Assignee:
RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK (230 West 41st Street, 7th floorNew York, New York, 10036, US)
UNIVERSITY OF STRATHCLYDE (McCance Building, 16 Richmond StreetGlasgow, G1 1XQ, GB)
BITTMAN, Robert (65-30 Kissena Blvd, Queens, New York, 11367-1597, US)
PYNE, Nigel J. (Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde161 Cathedral Street,Glasgow, G4 0RE, GB)
PYNE, Susan (Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde161 Cathedral Street,Glasgow, G4 0RE, GB)
BAEK, Dong Jae (194-60B 64th Ave #1A, Fresh Meadows, New York, 11365, US)
LIU, Zheng (1015 Essex street SE, #208Minneapolis, Minnesota, 55414, US)
BYUN, Hoe Sup (45-31 218th Street, Bayside, New York, 11361, US)
International Classes:
C07D401/04; C07C215/08; C07C275/28; C07C275/30; C07C335/16; C07D207/08; C07D211/14; C07D211/46; C07D249/06; C07D295/03; C07D295/037; C07D295/088; C07D295/096; C07D307/14; C07F9/38
Domestic Patent References:
WO2011016033A12011-02-10
WO2001094357A12001-12-13
WO2013049280A22013-04-04
Foreign References:
US6107520A2000-08-22
JPH0193562A1989-04-12
Other References:
DAVID MORMENEO ET AL: "Synthesis and preliminary antifungal evaluation of a library of phytosphingolipid analogues", ORGANIC & BIOMOLECULAR CHEMISTRY, vol. 5, no. 23, 1 January 2007 (2007-01-01), page 3769, XP055090185, ISSN: 1477-0520, DOI: 10.1039/b709421c
KOKATLA H P ET AL: "Stereoselective synthesis of safingol and its natural stereoisomer from d-glycals", TETRAHEDRON LETTERS, PERGAMON, GB, vol. 49, no. 32, 4 August 2008 (2008-08-04), pages 4728-4730, XP022776730, ISSN: 0040-4039, DOI: 10.1016/J.TETLET.2008.05.112 [retrieved on 2008-06-13]
LHERBET C ET AL: "Probing the stereochmistry of the active site of gamma-glutamyl transpeptidase using sulfur derivatives of L-glutamic acid", ORGANIC & BIOMOLECULAR CHEMISTRY, ROYAL SOCIETY OF CHEMISTRY, GB, vol. 2, no. 2, 1 January 2004 (2004-01-01) , pages 238-245, XP003013855, ISSN: 1477-0520, DOI: 10.1039/B310767A
BENJAMIN WEISS ET AL: "II. Synthesis of Long Chain Fatty Acid Amines of Sphingosine and Dihydrosphingosine 1", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 80, no. 17, 1 September 1958 (1958-09-01), pages 4657-4658, XP055115001, ISSN: 0002-7863, DOI: 10.1021/ja01550a061
HOE-SUP BYUN ET AL: "Novel sphingosine-containing analogues selectively inhibit sphingosine kinase (SK) isozymes, induce SK1 proteasomal degradation and reduce DNA synthesis in human pulmonary arterial smooth muscle cells", MEDCHEMCOMM, vol. 4, no. 10, 6 August 2013 (2013-08-06) , page 1394, XP055115004, ISSN: 2040-2503, DOI: 10.1039/c3md00201b
Attorney, Agent or Firm:
CHAPMAN, Paul (Marks & Clerk LLP, Atholl Exchange6 Canning Street,Edinburgh, EH3 8EG, GB)
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