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WO1998009668A3 - Inhibiteurs de la synthese de la phosphatidylcholine - Google Patents

Inhibiteurs de la synthese de la phosphatidylcholine 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
Application number
PCT/GB1997/002410
Other languages
English (en)
Other versions
WO1998009668A2 (fr
Inventor
George Simon Attard
Christopher Mcguigan
Patrick Anthony Riley
Original Assignee
Univ Southampton
George Simon Attard
Christopher Mcguigan
Patrick Anthony Riley
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 Univ Southampton, George Simon Attard, Christopher Mcguigan, Patrick Anthony Riley filed Critical Univ Southampton
Priority to AU41285/97A priority Critical patent/AU4128597A/en
Publication of WO1998009668A2 publication Critical patent/WO1998009668A2/fr
Publication of WO1998009668A3 publication Critical patent/WO1998009668A3/fr

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

Abstract

L'invention porte sur l'utilisation d'un composé amphiphile pour la fabrication d'un médicament inhibant la synthèse de la phosphatidylcholine. Ledit composé amphiphile présente les propriétés suivantes: (i) il comporte un groupe hydrophile de tête non ionique, cationique ou anionique, et un groupe hydrophobe de queue, (ii) le groupe de tête présente une section A et le groupe de queue présente une section B telles que le rapport B:A est inférieur à 0,7:1, (iii) le groupe de queue comporte une chaîne droite d'hydrocarbures présentant de 8 à 18 atomes de carbone, et (iv) le composé amphiphile présente un coefficient de séparation membrane/eau supérieur à 1 x 10-3.
PCT/GB1997/002410 1996-09-06 1997-09-08 Inhibiteurs de la synthese de la phosphatidylcholine WO1998009668A2 (fr)

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 (fr) 1998-03-12
WO1998009668A3 true WO1998009668A3 (fr) 1998-06-25

Family

ID=10799530

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1997/002410 WO1998009668A2 (fr) 1996-09-06 1997-09-08 Inhibiteurs de la synthese de la phosphatidylcholine

Country Status (3)

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

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
SK12442001A3 (sk) * 1999-03-05 2002-06-04 Metabasis Therapeutics, Inc. Cyklické fosforamidáty, spôsob ich prípravy a farmaceutické kompozície, ktoré ich obsahujú
US7205404B1 (en) 1999-03-05 2007-04-17 Metabasis Therapeutics, Inc. Phosphorus-containing prodrugs
EP1634886A3 (fr) * 1999-03-05 2006-03-29 Metabasis Therapeutics, Inc. Nouveaux promedicaments a teneur en phosphore
US6752981B1 (en) 1999-09-08 2004-06-22 Metabasis Therapeutics, Inc. Prodrugs for liver specific drug delivery
US6414159B2 (en) 2000-02-14 2002-07-02 Wako Pure Chemical Industries, Ltd. Method for preparation of a quaternary ammonium salt
US6875757B2 (en) * 2000-03-17 2005-04-05 University Of Tennessee Research Foundation LPA receptor agonists and antagonists and methods of use
FR2818547B1 (fr) 2000-12-22 2006-11-17 Oreal Nouveaux derives c-glycosides et utilisation
FR2818646B1 (fr) * 2000-12-22 2006-06-23 Oreal Nouveaux derives c-glycoside et utilisation
US10449210B2 (en) 2014-02-13 2019-10-22 Ligand Pharmaceuticals Inc. Prodrug compounds and their uses
EP3164136A4 (fr) 2014-07-02 2018-04-04 Ligand Pharmaceuticals, Inc. Composés de promédicaments et leurs utilisations
EP3737676B1 (fr) 2018-01-09 2024-03-06 Ligand Pharmaceuticals, Inc. Composés acétal et leurs utilisations thérapeutiques
CN112480036A (zh) * 2020-12-02 2021-03-12 天津理工大学 一种哌啶类离子液体表面活性剂及其制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0108565A2 (fr) * 1982-11-08 1984-05-16 Takeda Chemical Industries, Ltd. Phospholipides, leur production et leur utilisation
JPS60178816A (ja) * 1984-02-24 1985-09-12 Rikagaku Kenkyusho 制癌剤

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0108565A2 (fr) * 1982-11-08 1984-05-16 Takeda Chemical Industries, Ltd. Phospholipides, leur production et leur utilisation
JPS60178816A (ja) * 1984-02-24 1985-09-12 Rikagaku Kenkyusho 制癌剤

Non-Patent Citations (24)

* Cited by examiner, † Cited by third party
Title
ATTARD, G.S. ET AL: "Phase behaviour of novel phospholipid comounds", CHEMISTRY AND PHYSICS OF LIPIDS, vol. 76, no. 1, 1995, pages 41 - 48, XP002061928 *
BECKERS, D. ET AL: "Molecular targets of Miltefosine", DRUGS OF TODAY, vol. 30, no. suppl. B, 1994, pages 5 - 12, XP002046737 *
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 *
COY, E.A. ET AL: "Antiproliferative effects of amphiphilic molecules", INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY, vol. 12, no. 8, 1990, pages 871 - 881, XP002061930 *
DATABASE CHEMABS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; TAKAHASHI, N. ET AL: "Anticancer pharmaceuticals containing surfactants as active ingredients" *
DATABASE CHEMABS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; XP002061940 *
DATABASE WPI Week 8543, Derwent World Patents Index; AN 85-266689, XP002046739 *
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 *
DICK D L ET AL: "PHYSICOCHEMICAL BEHAVIOR OF CYTOTOXIC ETHER LIPIDS", BIOCHEMISTRY, 31 (35). 1992. 8252-8257., XP002061929 *
GEILEN, C.C. ET AL: "Phosphatidylcholine biosynthesis as a target for phospholipid analogues", ADV.EXP.MED.BIOL. (PLATELET-ACTIVATING FACTOR AND RELATED LIPID MEDIATORS 2), vol. 416, 1996, pages 333 - 336, XP002061924 *
HILLYARD, L.A. ET AL: "Membrane proliferation and phosphatidylcholine synthesis in normal, preneoplastic and neoplastic mammary gland tissues in C3H mice", CANCER RESEARCH, vol. 32, no. 12, 1972, pages 2834 - 2842, XP002061936 *
KELLEY, E.E. ET AL: "Unidirectional membrane uptake of the ether lipid antineoplastic agent Edelfosine by L1210 cells", BIOCHEMICAL PHARMACOLOGY, vol. 45, no. 2, 1993, pages 2435 - 2439, XP002046738 *
KUCZERA, J. ET AL: "Effects of some cyclic elements containing amphiphilic compounds on stability and transport properties of model lecithin membranes", GENERAL PHYSIOLOGY AND BIOPHYSICS, vol. 6, no. 6, December 1987 (1987-12-01), pages 645 - 654, XP002061939 *
LOE, D.W. ET AL: "Interaction of multidrug-resistant Chinese hamster ovary cells with amphiphiles", BRITISH JOURNAL OF CANCER, vol. 68, no. 2, 1993, pages 342 - 351, XP002061931 *
MACKENZIE, A.N.: "The synthesis of novel phospholipids (HIV-1, immune deficiency, antineoplastic agents).", DISSERTATION ABSTRACTS INTERNATIONAL, vol. 57, no. 3-C, 1995, pages 947, XP002061927 *
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 (fr) 1998-03-12
GB9618634D0 (en) 1996-10-16

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