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WO1998009668A3 - Use of amphiphiles as phosphatidyl choline synthesis inhibitors - Google Patents

Use of amphiphiles as phosphatidyl choline synthesis inhibitors Download PDF

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Publication number
WO1998009668A3
WO1998009668A3 PCT/GB1997/002410 GB9702410W WO9809668A3 WO 1998009668 A3 WO1998009668 A3 WO 1998009668A3 GB 9702410 W GB9702410 W GB 9702410W WO 9809668 A3 WO9809668 A3 WO 9809668A3
Authority
WO
WIPO (PCT)
Prior art keywords
amphiphiles
phosphatidyl choline
synthesis inhibitors
amphiphilic compound
group
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/GB1997/002410
Other languages
French (fr)
Other versions
WO1998009668A2 (en
Inventor
George Simon Attard
Christopher Mcguigan
Patrick Anthony Riley
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Southampton
Original Assignee
University of Southampton
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University of Southampton filed Critical University of Southampton
Priority to AU41285/97A priority Critical patent/AU4128597A/en
Publication of WO1998009668A2 publication Critical patent/WO1998009668A2/en
Publication of WO1998009668A3 publication Critical patent/WO1998009668A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/665—Phosphorus compounds having oxygen as a ring hetero atom, e.g. fosfomycin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7008—Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7024—Esters of saccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/765—Polymers containing oxygen
    • A61K31/77—Polymers containing oxygen of oxiranes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/08—Esters of oxyacids of phosphorus
    • C07F9/09—Esters of phosphoric acids
    • C07F9/091—Esters of phosphoric acids with hydroxyalkyl compounds with further substituents on alkyl
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
    • C07F9/6574—Esters of oxyacids of phosphorus
    • C07F9/65742—Esters of oxyacids of phosphorus non-condensed with carbocyclic rings or heterocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • C07F9/65848—Cyclic amide derivatives of acids of phosphorus, in which two nitrogen atoms belong to the ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H3/00—Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms
    • C07H3/06—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
    • A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
    • A61K9/1272—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pyrrole Compounds (AREA)

Abstract

Use of an amphiphilic compound in the manufacture of a medicament for the inhibition of phosphatidylcholine synthesis, said amphiphilic compound have the following properties: i) the compound copmprises a non-ionic, cationic or anionic hydrophilic head group and a hydrophobic tail group; ii) the head group has a cross section A and the tail group has a cross section B such that the ratio B:A is less than 0.7:1; iii) the tail group comprises a straight hydrocarbon chain having from 8 to 18 carbon atoms; and iv) the amphiphilic compound has a membrane/water partition coefficient of more than 1 x 10-3.
PCT/GB1997/002410 1996-09-06 1997-09-08 Use of amphiphiles as phosphatidyl choline synthesis inhibitors Ceased WO1998009668A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU41285/97A AU4128597A (en) 1996-09-06 1997-09-08 Phosphatidylcholine synthesis inhibitors

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9618634.1 1996-09-06
GBGB9618634.1A GB9618634D0 (en) 1996-09-06 1996-09-06 Anti cancer drugs

Publications (2)

Publication Number Publication Date
WO1998009668A2 WO1998009668A2 (en) 1998-03-12
WO1998009668A3 true WO1998009668A3 (en) 1998-06-25

Family

ID=10799530

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1997/002410 Ceased WO1998009668A2 (en) 1996-09-06 1997-09-08 Use of amphiphiles as phosphatidyl choline synthesis inhibitors

Country Status (3)

Country Link
AU (1) AU4128597A (en)
GB (1) GB9618634D0 (en)
WO (1) WO1998009668A2 (en)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6312662B1 (en) 1998-03-06 2001-11-06 Metabasis Therapeutics, Inc. Prodrugs phosphorus-containing compounds
EP1634886A3 (en) * 1999-03-05 2006-03-29 Metabasis Therapeutics, Inc. Novel phosphorus-containing prodrug
IL145052A0 (en) * 1999-03-05 2002-06-30 Metabasis Therapeutics Inc Novel phosphorus-containing prodrugs
US7205404B1 (en) 1999-03-05 2007-04-17 Metabasis Therapeutics, Inc. Phosphorus-containing prodrugs
JP4979866B2 (en) 1999-09-08 2012-07-18 リガンド・ファーマシューティカルズ・インコーポレイテッド Prodrug for drug delivery specific to the liver
US6414159B2 (en) 2000-02-14 2002-07-02 Wako Pure Chemical Industries, Ltd. Method for preparation of a quaternary ammonium salt
PT1263752E (en) 2000-03-17 2008-03-18 Univ Tennessee Res Corp Lpa receptor agonists and antagonists and methods of use
FR2818547B1 (en) 2000-12-22 2006-11-17 Oreal NOVEL C-GLYCOSIDE DERIVATIVES AND USE
FR2818646B1 (en) * 2000-12-22 2006-06-23 Oreal NOVEL C-GLYCOSIDE DERIVATIVES AND USE
CN106061984A (en) 2014-02-13 2016-10-26 配体药物公司 Prodrug compounds and uses thereof
JP2017520545A (en) 2014-07-02 2017-07-27 リガンド・ファーマシューティカルズ・インコーポレイテッド Prodrug compounds and their use
CN111788196A (en) 2018-01-09 2020-10-16 配体药物公司 Acetal compounds and their therapeutic uses
CN112480036A (en) * 2020-12-02 2021-03-12 天津理工大学 Piperidine ionic liquid surfactant and preparation method thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0108565A2 (en) * 1982-11-08 1984-05-16 Takeda Chemical Industries, Ltd. Phospholipids, their production and use thereof
JPS60178816A (en) * 1984-02-24 1985-09-12 Rikagaku Kenkyusho Carcinostatic agent

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0108565A2 (en) * 1982-11-08 1984-05-16 Takeda Chemical Industries, Ltd. Phospholipids, their production and use thereof
JPS60178816A (en) * 1984-02-24 1985-09-12 Rikagaku Kenkyusho Carcinostatic agent

Non-Patent Citations (24)

* Cited by examiner, † Cited by third party
Title
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BOGGS, KEVIN P. ET AL: "Lysophosphatidylcholine and 1-O-Octadecyl-2-O-Methyl-rac-Glycero-3-Phosphocholine inhibit the CDP-Choline pathway of phosphatidylcholine synthesis at the CTP:Phosphocholine Cytidylyltransferase step", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 270, no. 13, 31 March 1995 (1995-03-31), pages 7757 - 7764, XP002061925 *
BOURNE RK: "CHEMICAL SYNTHESIS AND ANTITUMOR ACTIVITY OF PHOSPHOGLYCERIDE MUSTARDS.", DISS ABSTR INT (SCI);37(5):2261-B-2262-B 1976, XP002061935 *
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DELLINGER, M. ET AL: "Structural requirements of simple organic cations for recognition by multidrug resistant cells", CANCER RESEARCH, vol. 52, no. 22, 15 November 1992 (1992-11-15), pages 6385 - 6389, XP002061932 *
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MATSUMOTO, Y. ET AL: "Specific hybrid liposomes composed of phosphatidylcholine and polyoxyethylenealkyl ether with markedly enhanced imnhibitory effects on the growth of tumor cells in vitro", BIOLOGICAL AND PHARMACEUTICAL BULLETIN, vol. 18, no. 10, October 1995 (1995-10-01), pages 1456 - 8, XP000537683 *
NISHISAKI, H. ET AL: "Inhibitory effects of antitumor drugs on phosphatidylcholine synthesis and its reversal by teprenone in isolated guinea pig gastric glands", IGAKU NO AYUMI, vol. 155, no. 10, 1990, pages 669 - 670 *
PLANTAVID M ET AL: "CATIONIC AMPHIPHILIC DRUGS AS A POTENTIAL TOOL FOR MODIFYING PHOSPHOLIPIDS OF TUMOR CELLS. AN IN VITRO STUDY OF CHLORPROMAZINE EFFECTS ON KREBS II ASCITES CELLS", BIOCHEM PHARMACOL;30(4):293-297 1981, XP002061926 *
RAYNOR R.L. ET AL: "Membrane interactions of amphiphilic polypeptides mastoparan, melittin, polymyxin B, and cardiotoxin", J. BIOL. CHEM., 1991, 266/5 (2753-2758), USA, XP002061934 *
READ, GEORGE W. ET AL: "Competitive inhibition of 48/80-induced histamine release by benzalkonium chloride and its analogs and the polyamine receptor in mast cells", THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 222, no. 3, 1982, pages 652 - 7, XP002061938 *
ROTENBERG, S.A. ET AL: "Inhibition of rodent protein kinase C by the anticarcinoma agent dequalinium", CANCER RESEARCH, vol. 50, no. 3, 1990, pages 677 - 685, XP002061933 *
WIEDER,T. ET AL: "The effect of two synthetic phospholipids on cell proliferation and phosphatidylcholine biosynthesis in Madin-Darby canine kidney cells", LIPIDS, vol. 30, no. 5, 1995, pages 389 - 393, XP002061923 *
WOOD, S.J. ET AL: "Selective inhibition of A.beta fibril formation", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 271, no. 8, 23 February 1996 (1996-02-23), pages 4086 - 4092, XP002061937 *

Also Published As

Publication number Publication date
AU4128597A (en) 1998-03-26
WO1998009668A2 (en) 1998-03-12
GB9618634D0 (en) 1996-10-16

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