WO2014118556A3 - Selective inhibitors and allosteric activators of sphingosine kinase - Google Patents

Selective inhibitors and allosteric activators of sphingosine kinase Download PDF

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WO2014118556A3
WO2014118556A3 PCT/GB2014/050264 GB2014050264W WO2014118556A3 WO 2014118556 A3 WO2014118556 A3 WO 2014118556A3 GB 2014050264 W GB2014050264 W GB 2014050264W WO 2014118556 A3 WO2014118556 A3 WO 2014118556A3
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Prior art keywords
sphingosine kinase
selective inhibitors
sphingosine
allosteric activators
inhibitors
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PCT/GB2014/050264
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French (fr)
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WO2014118556A2 (en
Inventor
Robert Bittman
Nigel J. PYNE
Susan Pyne
Dong Jae Baek
Zheng Liu
Hoe Sup BYUN
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Research Foundation Of The City University Of New York
University Of Strathclyde
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Publication of WO2014118556A2 publication Critical patent/WO2014118556A2/en
Publication of WO2014118556A3 publication Critical patent/WO2014118556A3/en

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    • C07D295/037—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements with quaternary ring nitrogen atoms
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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
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  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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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.
PCT/GB2014/050264 2013-01-31 2014-01-31 Selective inhibitors and allosteric activators of sphingosine kinase WO2014118556A2 (en)

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US201361759393P 2013-01-31 2013-01-31
US61/759,393 2013-01-31

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WO2014118556A3 true WO2014118556A3 (en) 2014-09-25

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US10583115B2 (en) 2014-10-08 2020-03-10 University Of South Australia Modulators of 14-3-3 functionality and uses thereof
WO2016085933A1 (en) 2014-11-24 2016-06-02 The Board Of Trustees Of The University Of Illinois Method of preventing or treating a pulmonary disease or condition
US10822415B2 (en) 2016-01-28 2020-11-03 Inserm (Institut National De La Santéet De La Recherche Médicale) Methods for enhancing the potency of the immune checkpoint inhibitors
US20170305861A1 (en) * 2016-04-25 2017-10-26 Immunomet Therapeutics, Inc Heteroaryl compounds comprising nitrogen and use thereof
EP3500308A4 (en) * 2016-08-18 2020-04-22 Memorial Sloan Kettering Cancer Center Inhibition of sphingosine 1-phosphate receptor for treatment and prevention of lymphedema
US20210080467A1 (en) 2018-02-21 2021-03-18 INSERM (Institut National de la Santé et de la Recherche Médicale) Use of sk1 as biomarker for predicting response to immunecheckpoint inhibitors

Citations (5)

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US6107520A (en) * 1997-04-15 2000-08-22 The Board Of Trustees Of The University Of Illinois Spisulosine compounds
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WO2011016033A1 (en) * 2009-08-04 2011-02-10 Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. Amino-alcohol analogues and uses thereof
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JPH0193562A (en) * 1987-10-05 1989-04-12 Shionogi & Co Ltd Production of sphingosine derivative
US6107520A (en) * 1997-04-15 2000-08-22 The Board Of Trustees Of The University Of Illinois Spisulosine compounds
WO2001094357A1 (en) * 2000-06-06 2001-12-13 Pharma Mar, S.A. Antitumoral compounds
WO2011016033A1 (en) * 2009-08-04 2011-02-10 Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. Amino-alcohol analogues and uses thereof
WO2013049280A2 (en) * 2011-09-29 2013-04-04 Emory University Sphingosine analogs, compositions, and methods related thereto

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Title
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 *
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), pages 3769, XP055090185, ISSN: 1477-0520, DOI: 10.1039/b709421c *
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), pages 1394, XP055115004, ISSN: 2040-2503, DOI: 10.1039/c3md00201b *
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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 *

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