WO1995029915A1 - Dihydro ou tetrahydroporphyrines derivees du polyethyleneglycol, leur preparation et leur utilisation en tant que composes de photosensibilisation servant a localiser des tumeurs - Google Patents

Dihydro ou tetrahydroporphyrines derivees du polyethyleneglycol, leur preparation et leur utilisation en tant que composes de photosensibilisation servant a localiser des tumeurs Download PDF

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Publication number
WO1995029915A1
WO1995029915A1 PCT/GB1995/000998 GB9500998W WO9529915A1 WO 1995029915 A1 WO1995029915 A1 WO 1995029915A1 GB 9500998 W GB9500998 W GB 9500998W WO 9529915 A1 WO9529915 A1 WO 9529915A1
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WO
WIPO (PCT)
Prior art keywords
compounds
tumour
group
derivatised
dihydro
Prior art date
Application number
PCT/GB1995/000998
Other languages
English (en)
Inventor
Davd Frederick Horrobin
Brenda Elisabeth Reynolds
Original Assignee
Scotia Holdings Plc
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 Scotia Holdings Plc filed Critical Scotia Holdings Plc
Priority to JP7528083A priority Critical patent/JPH09512544A/ja
Priority to NZ284552A priority patent/NZ284552A/en
Priority to AU23172/95A priority patent/AU2317295A/en
Priority to EP95916810A priority patent/EP0758331A1/fr
Publication of WO1995029915A1 publication Critical patent/WO1995029915A1/fr
Priority to NO964635A priority patent/NO964635L/no
Priority to KR1019960706199A priority patent/KR970702862A/ko

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • This invention relates to polyether-substituted photosensitising compounds and their use in the treatment of tumours.
  • Photodynamic therapy involves the administration of a photosensitising compound followed by irradiation of the tissue containing the compound with visible light of a specific wavelength.
  • the resulting activated compound with oxygen, forms a reactive radical which causes necrosis of the surrounding tissue.
  • tumour localisation can also be used as a diagnostic tool for determination of tumour position, size etc. and thus of the treatment of choice.
  • Certain photosensitisers can be used as diagnostic tools, if applicable as sources of detectable fluorescence.
  • certain radio-labelled entities can also be incorporated into the tumour localising compounds for the purpose of diagnosis.
  • a group of photosensitising compounds have previously been the subject of EP 0 337 601 Al. These compounds are dihydroporphyrins (chlorins) (1) and the corresponding tetrahydro porphyrins (bacteriochlorins) (2) and (3) of the formulae:
  • Said substituent groups may be in the same or different positions on their respective phenyl groups and may be free, substituted, or partly substituted, for example with alkyl or acyl groups containing 1 to 4 carbon atoms.
  • the nucleus or the phenyl rings may be substituted further, provided pharmacological tolerability, appreciable solubility in water-based pharmacologically acceptable solutions (required so that the drug may be administered intravenously to ensure rapid distribution to the tumour), absorption of light at the red end of the visible spectrum, and take up in cancerous tissue are retained.
  • Such further substituted compounds when derivatised as discussed below, are regarded as forms of the compounds of the innovation and included in the scope of the claims herein.
  • Any of the compounds may be in the form of their salts at acidic or basic centres, or their metal complexes (e.g. Zn, Ga), or their hydrates or other solvates particularly with lower, e.g. C - C4, aliphatic alcohols.
  • the present invention concerns the derivatisation or partial derivatisation of the phenolic hydroxyl groups of compounds of formulae (1), (2) and (3) with polyethylene glycols with or without a linking group, the terminal hydroxyl being etherified or esterified with alkyl or acyl groups, the methyl group being the most preferred.
  • the group Y may be a Cj - Cj2 alkyl or acyl group but preferably a methyl group.
  • the linking group X may be present or absent, but if present may be of the following alternative forms: -
  • the chain length of the terminally substituted polyethylene glycol chains is such as to provide compounds of types (4), (5) and (6) of overall molecular weight of no less than 5,000 D and no more than 20,000 D which is the exclusion limit of the kidneys.
  • any free hydroxyl groups may be otherwise derivatised and salts with mineral acids (ie. hydrochlorides, sulphates, etc), metal complexes (ie. with Zn, Ga, etc), hydrates and solvates with lower (C ⁇ - C4) alcohols may be formed. All such forms are included in the claims therein.
  • the derivatised dihydro and tetrahydro porphyrin compounds (4), (5) and (6) have the following properties:
  • Dosages are such as to give the desired chlorin/bacteriochlorin concentration in the tumour and are between 0.01 mg/kg up to 100 mg/kg depending on the drug.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

Ces composés sont des dihydro ou tétrahydroporphorines dérivées du polyéthylèneglycol, acceptables sur le plan pharmacologique, servant à localiser des tumeurs et répondant aux formules (4), (5) et (6) dans lesquelles R1n peut représenter -OH mais, dans au moins deux cas, représente une chaîne de formule (-O-Xp-[CH2CH2O]m-Y)n dans laquelle n vaut 1 à 3, m vaut 5 à 250 et p vaut 0 à 1; le groupe Y peut représenter un groupe acyle ou alcoyle C1-12 mais représente, de préférence, un groupe méthyle; le groupe de liaison X peut être présent ou absent, mais s'il est présent, il peut représenter l'une des formes suivantes: R2 = -(C=O)-(CH¿2?)q-O- où q vaut 1 à 5, R?3¿ = -CH¿2?-CH(OH)-(CH2)s-O- où s vaut 1 à 4, R?4¿ = -(C=O)-(CH¿2?)t-(C=O)-O- où t vaut 1 à 4. Ces composés de photosensibilisation à substitution polyéther permettent de mieux localiser les tumeurs grâce à leur pénétration plus efficace à l'intérieur des cellules tumorales. Des doses globalement inférieures de médicament permettent d'améliorer le profil d'effets secondaires du traitement, notamment en égard à la photosensibilisation de la peau.
PCT/GB1995/000998 1994-05-03 1995-05-02 Dihydro ou tetrahydroporphyrines derivees du polyethyleneglycol, leur preparation et leur utilisation en tant que composes de photosensibilisation servant a localiser des tumeurs WO1995029915A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
JP7528083A JPH09512544A (ja) 1994-05-03 1995-05-02 腫瘍部位判定光増感化合物
NZ284552A NZ284552A (en) 1994-05-03 1995-05-02 Dihydro and tetrahydro porphyrin derivatives, preparation, and use in photosensitising composition
AU23172/95A AU2317295A (en) 1994-05-03 1995-05-02 Polyethylene glycol derivatised dihydro or tetrahydro porphyrins, their preparation and their use as tumour localising, photosensitising compounds
EP95916810A EP0758331A1 (fr) 1994-05-03 1995-05-02 Dihydro ou tetrahydroporphyrines derivees du polyethyleneglycol, leur preparation et leur utilisation en tant que composes de photosensibilisation servant a localiser des tumeurs
NO964635A NO964635L (no) 1994-05-03 1996-11-01 Polyetylenglykolderivatiserte dihydro- eller tetrahydro-porfyriner, deres fremstilling og deres anvendelse som tumorlokaliserende, fotosensitiviserende forbindelser
KR1019960706199A KR970702862A (ko) 1994-05-03 1996-11-02 폴리에틸렌글리콜 유도된 디하이드로 또는 테트라하이드로 포르피린, 이의 제조방법 및 종양에 위치되는 광감작 화합물로서 이의 용도(polyethylene glycol derivatised dihydro or tetrahydro porphyrins, their preparation and their use as tumour localising, photosensitising compounds)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9408746.7 1994-05-03
GB9408746A GB9408746D0 (en) 1994-05-03 1994-05-03 Tumour locallising photosensitising compounds

Publications (1)

Publication Number Publication Date
WO1995029915A1 true WO1995029915A1 (fr) 1995-11-09

Family

ID=10754481

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1995/000998 WO1995029915A1 (fr) 1994-05-03 1995-05-02 Dihydro ou tetrahydroporphyrines derivees du polyethyleneglycol, leur preparation et leur utilisation en tant que composes de photosensibilisation servant a localiser des tumeurs

Country Status (11)

Country Link
EP (1) EP0758331A1 (fr)
JP (1) JPH09512544A (fr)
KR (1) KR970702862A (fr)
AU (1) AU2317295A (fr)
CA (1) CA2189435A1 (fr)
GB (1) GB9408746D0 (fr)
NO (1) NO964635L (fr)
NZ (1) NZ284552A (fr)
TW (1) TW397836B (fr)
WO (1) WO1995029915A1 (fr)
ZA (1) ZA953560B (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0723548A1 (fr) * 1993-10-15 1996-07-31 The Trustees Of The University Of Pennsylvania Composes phosphorescents pour visualiser l'oxygene dans les tissus
WO1996032134A2 (fr) * 1995-04-13 1996-10-17 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Conjugue comprenant un principe actif, un polyether et eventuellement une proteine a l'etat natif non consideree comme exogene
WO1998001156A2 (fr) * 1996-07-05 1998-01-15 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Procede de production de chlorines et bacteriochlorines contenant un polyether
WO2001066550A2 (fr) * 2000-03-10 2001-09-13 Scotia Holdings Plc Composes pour therapie photodynamique
US6630128B1 (en) 1998-08-28 2003-10-07 Destiny Pharma Limited Porphyrin derivatives their use in photodynamic therapy and medical devices containing them
US7026488B2 (en) * 2001-08-31 2006-04-11 Hiroshi Maeda Antitumor agents and process for producing the same
CN108715591A (zh) * 2018-06-01 2018-10-30 华东理工大学 用作光敏剂的近红外吸收卟啉化合物及其应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0186962A1 (fr) * 1984-11-26 1986-07-09 Efamol Limited Porphyrines et traitement du cancer
EP0337601A1 (fr) * 1988-03-11 1989-10-18 Scotia Holdings Plc Porphyrines et medicaments pour le traitement de cancer
WO1991018630A1 (fr) * 1990-05-30 1991-12-12 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Agents anti-tumoraux substitues avec du polyether

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0186962A1 (fr) * 1984-11-26 1986-07-09 Efamol Limited Porphyrines et traitement du cancer
EP0337601A1 (fr) * 1988-03-11 1989-10-18 Scotia Holdings Plc Porphyrines et medicaments pour le traitement de cancer
WO1991018630A1 (fr) * 1990-05-30 1991-12-12 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Agents anti-tumoraux substitues avec du polyether

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6362175B1 (en) 1991-09-20 2002-03-26 The Trustees Of The University Of Pennsylvania Porphyrin compounds for imaging tissue oxygen
EP0723548A1 (fr) * 1993-10-15 1996-07-31 The Trustees Of The University Of Pennsylvania Composes phosphorescents pour visualiser l'oxygene dans les tissus
EP0723548A4 (fr) * 1993-10-15 1997-01-15 Univ Pennsylvania Composes phosphorescents pour visualiser l'oxygene dans les tissus
WO1996032134A2 (fr) * 1995-04-13 1996-10-17 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Conjugue comprenant un principe actif, un polyether et eventuellement une proteine a l'etat natif non consideree comme exogene
WO1996032134A3 (fr) * 1995-04-13 1996-11-14 Deutsches Krebsforsch Conjugue comprenant un principe actif, un polyether et eventuellement une proteine a l'etat natif non consideree comme exogene
US6150327A (en) * 1995-04-13 2000-11-21 Deutsches Krebsforschungszentrum Stiftund Des Offentlichen Rechts Conjugate of an active agent, a polyether and possibly a native protein regarded as acceptable by the body
US6147207A (en) * 1996-07-05 2000-11-14 Deutsches Krebsforschungszentrum Stiftung Des Offentlichen Method for producing chlorins and bacteriochlorins containing polyether
WO1998001156A3 (fr) * 1996-07-05 1998-04-09 Deutsches Krebsforsch Procede de production de chlorines et bacteriochlorines contenant un polyether
WO1998001156A2 (fr) * 1996-07-05 1998-01-15 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Procede de production de chlorines et bacteriochlorines contenant un polyether
US6630128B1 (en) 1998-08-28 2003-10-07 Destiny Pharma Limited Porphyrin derivatives their use in photodynamic therapy and medical devices containing them
WO2001066550A2 (fr) * 2000-03-10 2001-09-13 Scotia Holdings Plc Composes pour therapie photodynamique
WO2001066550A3 (fr) * 2000-03-10 2001-12-20 Scotia Holdings Plc Composes pour therapie photodynamique
US7375215B2 (en) 2000-03-10 2008-05-20 Bioscience Technology Investment Holdings Limited Compounds for PDT
US7026488B2 (en) * 2001-08-31 2006-04-11 Hiroshi Maeda Antitumor agents and process for producing the same
CN108715591A (zh) * 2018-06-01 2018-10-30 华东理工大学 用作光敏剂的近红外吸收卟啉化合物及其应用

Also Published As

Publication number Publication date
KR970702862A (ko) 1997-06-10
AU2317295A (en) 1995-11-29
GB9408746D0 (en) 1994-06-22
NO964635D0 (no) 1996-11-01
CA2189435A1 (fr) 1995-11-09
NO964635L (no) 1996-11-01
ZA953560B (en) 1996-01-11
NZ284552A (en) 1997-12-19
TW397836B (en) 2000-07-11
EP0758331A1 (fr) 1997-02-19
JPH09512544A (ja) 1997-12-16

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