WO2004002476B1 - Fluorinated chlorin and bacteriochlorin photosensitizers for photodynamic therapy - Google Patents

Fluorinated chlorin and bacteriochlorin photosensitizers for photodynamic therapy

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Publication number
WO2004002476B1
WO2004002476B1 PCT/US2003/020427 US0320427W WO2004002476B1 WO 2004002476 B1 WO2004002476 B1 WO 2004002476B1 US 0320427 W US0320427 W US 0320427W WO 2004002476 B1 WO2004002476 B1 WO 2004002476B1
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Prior art keywords
compound
substituted
alkyl
pharmaceutically acceptable
acceptable derivative
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Application number
PCT/US2003/020427
Other languages
French (fr)
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WO2004002476A3 (en
WO2004002476A2 (en
WO2004002476A9 (en
Inventor
Ravindra K Pandey
William R Potter
Thomas J Dougherty
Original Assignee
Health Research Inc
Ravindra K Pandey
William R Potter
Thomas J Dougherty
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.)
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Application filed by Health Research Inc, Ravindra K Pandey, William R Potter, Thomas J Dougherty filed Critical Health Research Inc
Priority to EP03762180A priority Critical patent/EP1517684B1/en
Priority to DE60328496T priority patent/DE60328496D1/en
Priority to AU2003248747A priority patent/AU2003248747A1/en
Priority to CA002490692A priority patent/CA2490692A1/en
Publication of WO2004002476A2 publication Critical patent/WO2004002476A2/en
Publication of WO2004002476A9 publication Critical patent/WO2004002476A9/en
Publication of WO2004002476A3 publication Critical patent/WO2004002476A3/en
Publication of WO2004002476B1 publication Critical patent/WO2004002476B1/en
Priority to US12/378,751 priority patent/US7820143B2/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed systems contains four or more hetero rings
    • 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
    • A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
    • 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
    • A61K41/0076—PDT with expanded (metallo)porphyrins, i.e. having more than 20 ring atoms, e.g. texaphyrins, sapphyrins, hexaphyrins, pentaphyrins, porphocyanines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B47/00—Porphines; Azaporphines
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B69/00—Dyes not provided for by a single group of this subclass
    • C09B69/10—Polymeric dyes; Reaction products of dyes with monomers or with macromolecular compounds
    • C09B69/108—Polymeric dyes; Reaction products of dyes with monomers or with macromolecular compounds containing a phthalocyanine dye

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Radiation-Therapy Devices (AREA)

Abstract

Provided herein are tetrapyrrole compounds containing a fluorinated substituent for detection, diagnosis and treatment of target tissues or target compositions, including hyperproliferative tissues such as tumors, using photodynamic methods. In particular, photosensitizer compounds that collect in hyperproliferative tissue are provided. In another embodiment, compounds that absorb light at a wavelength of from about 700 to about 850 nm are provided. In a further embodiment, compounds that are detectable by magnetic resonance imaging are provided.

Claims

AMENDED CLAIMS[received by the International Bureau on 26 April 2004 (26.04.04); original claims 1-56 replaced by amended claims 1-54 (18 pages)]Amendments under Article 19(1) PCT:
1. A compound of the formula:
Figure imgf000002_0001
or a pharmaceutically acceptable derivative thereof, wherein:
R-t, R-ia, 2> 2a, R3, βa. R4. R4a, R5, Re, δa, e, δa> R9, and R10 are independently hydrogen, lower alkyl of about 1 through 8 carbon atoms, lower alkenyl of about 1 through 8 carbon atoms, or lower alkyl of about 1 through 8 carbon atoms substituted with at least one halogen, hydroxy, carboxy, ester, aromatic, heterocyclic, ether, amide, or amine group; where two R-i, Rιa, R2, R2a> R4, R4a, Re, Rθa, δ> Rβa 9 and R10 groups on adjacent carbon atoms may be taken together to form a covalent bond or two R-i, Rιa, R2, R2a> R3, R3a> R4, R4a, RΘ, Rδa, Rβ> and Rβa groups on the same carbon atom may form a double bond to a divalent pendant group; R1 or R2 may additionally be -CH=CH2, -CHO, -COOH, -COORa , or
H3C OR 1 1
R7 is -CH2-, or-N(Ri2)-, where
R11 is lower alkyl of about 1 through 8 carbon atoms, lower alkenyl of about 1 through 8 carbon atoms, or lower alkyl of about 1 through 8 carbon atoms substituted with at least one halogen, hydroxy, carboxy, ester, aromatic, heterocyclic, ether, amide, or amine group; and 108
Ri2 is hydrogen, lower alkyl of about 1 through 8 carbon atoms, lower alkenyl of about 1 through 8 carbon atoms, or lower alkyl of about 1 through 8 carbon atoms substituted with at least one halogen, hydroxy, carboxy, ester, aromatic, heterocyclic, ether, amide, or amine group;_ provided that at least one of R1 f Rιa, R2, R2a Rδ, Rδa, R4, R4a, R5, R5, Re, Rβa R7, Rδ, Rδa, R9 and R10 contains at least one fluorinated pendant group selected from the group consisting of fluorinated alkyl groups, fluorinated phenyl groups and fluorinated heterocyclic moieties.
2. The compound of claim 1 wherein Rg is -CH2CH2CO2Ra, where Ra is hydrogen or lower alkyl of 1-8 carbons.
3. A compound of the formula:
Figure imgf000003_0001
or a pharmaceutically acceptable derivative thereof, wherein:
R1 and R2 are each independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, -C(O)Ra or -COORa, where Ra is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted cycloalkyl;
Ria and R2a are each independently hydrogen or substituted or unsubstituted alkyl, or together form a covalent bond;
R3 and R4 are each independently hydrogen or substituted or unsubstituted alkyl; 109
R3a and R4a are each independently hydrogen or substituted or unsubstituted alkyl, or together form a covalent bond;
R5 is hydrogen or substituted or unsubstituted alkyl;
Re and Rβa are each independently hydrogen or substituted or unsubstituted alkyl, or together form =O;
R7 is an alkylene, azaalkyl, or azaaralkyl;
Rs and Rsa are each independently hydrogen or substituted or unsubstituted alkyl, or together form =O;
Rg and Rio are each independently hydrogen, or substituted or unsubstituted alkyl; each of R1-R10, when substituted, is substituted with one or more substituents each independently selected from Q, where Q is alkyl, haloalkyl, halo, pseudohalo, aryl, heteroaryl, cycloalkyl, heterocyclyl, -COORb where Rb is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl,
ORc where Rc is alkyl, alkenyl, alkynyl, cycloalkyl, arallkyl, or aryl,
CONRdRe where Rd and Re are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl, NRfRg where Rf and Rg are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl or aryl,
=NRh where Rh is alkyl, alkenyl, alkynyl, cycloalkyl, aralkyl or aryl, or is an amino acid residue; each Q is independently unsubstituted or is substituted with one or more substituents each independently selected from Q-i, where Qi is alkyl, haloalkyl, halo, pseudohalo, aryl, heteroaryl, cycloalkyl, heterocyclyl,
-COORb where Rb is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl, ORc where Rc is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl,
CONRdRe where Rd and Re are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl, 110
NRfRg where Rf and Rg are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl, or is an amino acid residue; with the proviso that the compound contains at least one fluorine atom.
4. The compound of claim 3, wherein:
R-i is substituted or unsubstituted alkyl;
R2 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or -C(O)Ra, where Ra is substituted or unsubstituted alkyl;
R-ia and R2a together form a covalent bond; R3 and R4 are each independently substituted or unsubstituted alkyl;
R3a and R4a are each independently hydrogen, or together form a covalent bond;
R5 is substituted or unsubstituted alkyl;
R6 and Rea together form =O; R7 is azaalkyl, or azaaralkyl;
Rs and Rsa together form =O;
R9 and Rio are each independently substituted or unsubstituted alkyl; each of R1-R10, when substituted, is substituted with one or more substituents each independently selected from Q, where Q is halo, pseudohalo, haloalkyl,
COORb where Rb is hydrogen or alkyl,
ORc where Rc is alkyl or aralkyl,
NRfRg where Rf and Rg are each independently hydrogen, alkyl or aralkyl, or =NRh where Rh is aralkyl; each Q is independently unsubstituted or is substituted with one or more substituents each independently selected from Qi, where Qi is halo, pseudohalo, or haloalkyl.
5. The compound of claim 3 or claim 4, wherein: R1 is unsubstituted alkyl;
R2 is substituted or unsubstituted alkyl, unsubstituted alkenyl, or -C(O)Ra, where Ra is unsubstituted alkyl; 111
Ria and R2a together form a covalent bond;
R3 and R4 are each independently unsubstituted alkyl;
R3a and R4a are each independently hydrogen, or together form a covalent bond; R5 is unsubstituted alkyl;
Rδ and Rβa together form =O;
R7 is azaalkyl, or azaaralkyl;
Re and R8a together form =O;
Rg is substituted alkyl; R-io is unsubstituted alkyl; each of R1-R10, when substituted, is substituted with one or more substituents each independently selected from Q, where Q is halo, pseudohalo, haloalkyl, COORb where Rb is hydrogen or alkyl, ORc where Rc is alkyl or aralkyl, NRfRg where Rf and Rg are each independently hydrogen, alkyl or aralkyl, or =NRh where Rh is aralkyl; each Q is independently unsubstituted or is substituted with one or more substituents each independently selected from Qi, where Q-i is halo, pseudohalo, or haloalkyl.
6. The compound of any one of claims 3-5, wherein: R1 is methyl;
Rιa and R2a together form a covalent bond;
R3 is methyl;
R is ethyl;
R3a and R4a are each independently hydrogen, or together form a covalent bond;
R5 is methyl;
R9 is CH2CH2COOH or CH2CH2COOMe;
R10 is methyl.
7. The compound of any one of claims 3-6, wherein:
R2 is CH=CH2, CH(OR20)CH3, C(O)Me, C(=NR2t)CH3 or CH(NHR21)CH3; 112
where R20 is methyl, butyl, heptyl, dodecyl or 3,5-bis(trifluoromethyl)- benzyl; and
R21 is 3,5-bis(trifluoromethyl)benzyl.
8. The compound of any one of claims 3-7, wherein:
R is =NR2o, where R2o is methyl, butyl, heptyl, dodecyl or 3,5-bis(tri- f!uoromethyl)benzyl.
9. A compound of claim 3 having the formula:
Figure imgf000007_0001
or a pharmaceutically acceptable derivative thereof.
113
10. A compound of claim 3 having the formula:
Figure imgf000008_0001
or a pharmaceutically acceptable derivative thereof, wherein:
R is methyl, butyl, heptyl or dodecyl.
11. A compound of claim 3 having the formula:
Figure imgf000008_0002
or a pharmaceutically acceptable derivative thereof, wherein: R is methyl, butyl, heptyl or dodecyl. 114
12. A compound of claim 3 having the formula:
Figure imgf000009_0001
or a pharmaceutically acceptable derivative thereof.
13. A compound of claim 3 having the formula:
Figure imgf000009_0002
or a pharmaceutically acceptable derivative thereof, wherein: R is methyl, butyl, heptyl or dodecyl. 115
14. A compound of claim 3 having the formula:
Figure imgf000010_0001
or a pharmaceutically acceptable derivative thereof.
15. A compound of claim 3 having the formula:
Figure imgf000010_0002
or a pharmaceutically acceptable derivative thereof. 116
16. A compound of claim 3 having the formula
Figure imgf000011_0001
or a pharmaceutically acceptable derivative thereof, wherein:
X is an aryl or heteroaryl group;
R and R1 are each independently alkyl, aryl, or heteroaryl groups having 1 - 20 carbon atoms, wherein at least one of R and R1 is substituted with at least one fluorine atom; and
R2 is an alkyl group, optionally substituted with one or more fluorine atoms.
17. A compound of claim 3 having the formula
Figure imgf000011_0002
or a pharmaceutically acceptable derivative thereof, wherein: X is an aryl or heteroaryl group; n is an integer from 0 to 6; R and R1 are each independently alkyl, aryl, or heteroaryl groups having 1 - 20 carbon atoms, wherein at least one of R and R1 is substituted with at least one fluorine atom; and
R2 is an alkyl group, optionally substituted with one or more fluorine atoms.
18. A compound of claim 3 having the formula
Figure imgf000012_0001
or a pharmaceutically acceptable derivative thereof, wherein:
X is an aryl or heteroaryl group;
R and R1 are each independently alkyl, aryl, or heteroaryl groups having 1 - 20 carbon atoms, wherein at least one of R and R1 is substituted with at least one fluorine atom; and
R2 is an alkyl group, optionally substituted with one or more fluorine atoms.
118
19. A compound of claim 3 having the formula
Figure imgf000013_0001
or a pharmaceutically acceptable derivative thereof, wherein:
X is an aryl or heteroaryl group; n is an integer from 0 to 6;
R and R1 are each independently alkyl, aryl, or heteroaryl groups having 1 - 20 carbon atoms, wherein at least one of R and R1 is substituted with at least one fluorine atom; and
R2 is an alkyl group, optionally substituted with one or more fluorine atoms.
119
20. A compound of claim 3 having the formula
Figure imgf000014_0001
or a pharmaceutically acceptable derivative thereof, wherein:
X and Y are each independently an aryl or heteroaryl group; n is an integer from 0 to 6;
R and R1 are each independently alkyl, aryl, or heteroaryl groups having 1 - 20 carbon atoms, wherein at least one of R and R1 is substituted with at least one fluorine atom; and
R2 is an alkyl group, optionally substituted with one or more fluorine atoms.
21. A pharmaceutical composition, comprising a compound of any one of claims 1-20 or a pharmaceutically acceptable derivative thereof in a pharmaceutically acceptable carrier.
22. An article of manufacture, comprising packaging material and a compound of any one of claims 1-20 or a pharmaceutically acceptable derivative of a compound of any one of claims 1-20 contained within the packaging material, wherein the compound or salt thereof is effective in a photodynamic therapy treatment for ameliorating the symptoms of a hyperproliferative disorder; and the packaging material includes a label that indicates that the compound or 120
salt thereof is used in a photodynamic therapy treatment for ameliorating the symptoms of a hyperproliferative disorder.
23. The compound of any one of claims 1 - 20 or a pharmaceutically acceptable derivative thereof when used for the treatment of hyperproliferative tissue.
24. The compound of any one of claims 1 - 20 or a pharmaceutically acceptable derivative thereof when used to detect a hyperproliferative tissue.
25. The compound of any one of claims 15-17 or a pharmaceutically acceptable derivative thereof when used for the detection or treatment or both of hyperproliferative tissue.
26. The compound of any one of claims 1 - 20 or a pharmaceutically acceptable derivative thereof when used in a photodynamic therapy.
27. The compound of any one of claims 1 - 20 or a pharmaceutically acceptable derivative thereof when used to destroy a target composition within a subject.
28. Use of the compound of any one of claims 1 - 20 or a pharmaceutically acceptable derivative thereof for formulation of a medicament for the treatment of hyperproliferative disorders.
29. A method for administering a therapy to a target, comprising: (i) administering to a subject the compound of any one of claims 1 - 20 or a pharmaceutically acceptable derivative thereof that preferentially associates with the target, and
(ii) irradiating the subject with light of a wavelength and total fluence sufficient to produce a therapeutic effect.
30. The method of claim 29, wherein the target is selected from the group consisting of: a vascular endothelial tissue, a neovasculature tissue, a neovasculature tissue present in an eye, an abnormal vascular wall of a tumor, a 121
solid tumor, a tumor of a head, a tumor of a neck, a tumor of an eye, a tumor of a gastrointestinal tract, a tumor of a liver, a tumor of a breast, a tumor of a prostate, a tumors of a lung, a nonsolid tumor, malignant cells of one of a hematopoietic tissue and a lymphoid tissue, lesions in a vascular system, a diseased bone marrow, and diseased cells in which the disease is one of an autoimmune and an inflammatory disease.
31. The method of claim 29, wherein the target composition is selected from the group consisting of bacteria, viruses, fungi, protozoa, and toxins.
32. The method of claim 29, further comprising the step of allowing sufficient time for any of the compound that is not preferentially associated to the target tissue to clear from non-target tissue of the subject prior to the step of irradiating.
33. The method of claim 29 wherein the compound is conjugated to a targeting agent.
34. The method of claim 33 wherein the targeting agent is one of an antibody or an antibody fragment that is specific in binding with the target tissue.
35. The method of claim 33 wherein the targeting agent is a peptide that is specific in binding with the target tissue.
36. The method of claim 33, wherein the targeting agent is a liposomal preparation.
37. A method of photodynamic therapy for treating hyperproliferative tissue in a subject, comprising:
(i) administering to the subject the compound of any one of claims 1 - 20 or a pharmaceutically acceptable derivative thereof that preferentially associates with the hyperproliferative tissue, and 122
(ii) irradiating the subject with light of a wavelength and fluence sufficient to activate the compound, whereby the hyperproliferative tissue is destroyed or impaired.
38. A method for detecting the presence of a hyperproliferative tissue in a subject comprising:
(i) administering to the subject a sufficient quantity of the compound of any one of claims 1 - 20 or a pharmaceutically acceptable derivative thereof that preferentially associates with the hyperproliferative tissue; and
(ii) visualizing the compound within the patient.
39. The method of claim 38 wherein the step of visualizing is accomplished by generating an MRl image of at least a part of the patient's body.
40. The method of claim 38 wherein the step of visualizing is accomplished by exposing the conjugated compound with light of sufficient energy to cause the compound to fluoresce.
41. A method for detecting a target in a biological sample, comprising:
(i) adding to the biological sample the compound of any one of claims
1 - 20 or a pharmaceutically acceptable derivative thereof that binds to the target; and
(ii) detecting the compound.
42. The method of claim 41 , wherein the biological sample is selected from the group consisting of blood, urine, saliva, tears, synovial fluid, sweat, interstitial fluid, sperm, cerebrospinal fluid, ascites fluid, and/or tumor tissue biopsy and circulating tumor cells.
43. A method of diagnosing an infecting agent in a patient, comprising: (i) conjugating to any one of the compounds of claims 1 -20 or a pharmaceutically acceptable derivative thereof a targeting agent specific for the infecting agent, whereby a conjugated compound is formed; 123
(ii) administering to the patient the conjugated compound; and (iii) visualizing the conjugated compound within the patient.
44. The method of claim 43 wherein the step of visualizing is accomplished by generating a MRl image of at least a part of the patient's body.
45. The method of claim 43 wherein the step of visualizing is accomplished by exposing the conjugated compound with light of sufficient energy to cause the compound to fluoresce.
46. A method of generating an image of a target tissue or target composition in a subject, comprising: (i) administering to the subject the compound of any one of claims 1-20 or a pharmaceutically acceptable derivative thereof; and
(ii) generating an image of at least a part of the subject to which the compound has preferentially associated.
47. The method of claim 46 wherein the image is a nuclear imaging image.
48. A method of labeling a target tissue for diagnostic radiology, comprising:
(i) administering to a subject the compound of any one of claims 1-20 or a pharmaceutically acceptable derivative thereof; and (ii) allowing sufficient time for any compound that is not preferentially associated to the target tissue to clear from non-target tissue of the subject, whereby the target tissue can be distinguished from non-target tissue in an MRl image of the subject.
49. A method of providing a medical therapy to an animal, comprising: (i) administering to the animal the compound of any one of claims 1 - 20 or a pharmaceutically acceptable derivative thereof, and 124
(ii) irradiating the animal with light of a wavelength and fluence sufficient to activate the compound, whereby the hyperproliferative tissue is destroyed or impaired.
50. The compound of any one of claims 1-20 or a pharmaceutically acceptable derivative thereof when used for the labeling of a target tissue for diagnostic radiology.
51. A kit to treat hyperproliferative disorders, comprising the compound of any one of claims 1-20 or a pharmaceutically acceptable derivative thereof and instructions teaching a method of photodynamic therapy.
52. A kit to label specific tissues for diagnostic radiology, comprising the compound of any one of claims 1-20 or a pharmaceutically acceptable derivative thereof and instructions teaching a method of magnetic resonance imaging.
53. A combination, comprising: the compound of any one of claims 1-20 or a pharmaceutically acceptable derivative thereof; and a light source.
54. A combination, comprising: the compound of any one of claims 1-20 or pharmaceutically acceptable derivatives thereof; and a magnetic resonance imaging device.
PCT/US2003/020427 2002-06-27 2003-06-27 Fluorinated chlorin and bacteriochlorin photosensitizers for photodynamic therapy WO2004002476A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP03762180A EP1517684B1 (en) 2002-06-27 2003-06-27 Fluorinated chlorin and bacteriochlorin photosensitizers for photodynamic therapy
DE60328496T DE60328496D1 (en) 2002-06-27 2003-06-27 Fluorinierte chlorin und bacteriochlorin photosensitizer für fotodynamische therapie
AU2003248747A AU2003248747A1 (en) 2002-06-27 2003-06-27 Fluorinated chlorin and bacteriochlorin photosensitizers for photodynamic therapy
CA002490692A CA2490692A1 (en) 2002-06-27 2003-06-27 Fluorinated chlorin and bacteriochlorin photosensitizers for photodynamic therapy
US12/378,751 US7820143B2 (en) 2002-06-27 2009-02-19 Water soluble tetrapyrollic photosensitizers for photodynamic therapy

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US39247302P 2002-06-27 2002-06-27
US60/392,473 2002-06-27

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US7501509B2 (en) 2009-03-10
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