Porphycene compounds for photodynamic therapy

• US 5,179,120 A
• Filed: 06/28/1991
• Issued: 01/12/1993
• Est. Priority Date: 06/28/1991
• Status: Expired due to Fees

• Current Assignee: Cytopharm, Inc.
• Original Assignee: Cytopharm, Inc.
• Inventors: Muller, Martin, Richert, Clemens, Vogel, Emanuel, Cross, Alexander D., Benninghaus, Thomas
• Primary Examiner(s): Rizzo, Nicholas S.
• Assistant Examiner(s): VENKAT, JYOTHSNA A
• Application Number:
  US07/723,394
• Time in Patent Office: 564 Days
• Field of Search: 540/465, 540/472, 514/410
• US Class Current: 514/410
• CPC Class Codes: A61K 41/0057 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
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07D 487/22 in which the condensed system contains four or more hetero rings

Abstract

A porphycene having the structure ##STR1## wherein each R¹ is, independently, (a) --(CH₂)_n --X, where n=1-4, X is OR² and R² is C_1-6 alkyl, aralkyl or aryl; CN; OH; OSO₂ R² ; NH₂ ; NHR² ; NR₂² ; SH; SR² ; S(O)_1-2 R² ; COOH; CO₂ R² ; C(O)NH₂ ; C(O)NHR² ; C(O)NR₂² ; halogen; or CHO;

(b) --(CH₂)_m CH═CH₂ where m is 0-2; or

(c) --(CH₂)_n --O--G where G is a mono- or oligosaccharide;

(d) --(CH₂)_2n --X, where X is an amino acid, oligopeptide covalently bonded by an ether-, ester- or amine-bond or --Y--(CH₂)_n -porphycene² (porphycene² being a compound of the same structure and Y is a direct bond; --O--; or --CH═CH₂); or

(e) where one, two or three of the substituents R¹ are C_1-6 alkyl or aryl and the remaining substituents are as above under (a)-(d), and salts and metal complexes thereof. The porphycene compounds and pharmaceutical compositions containing the compounds are useful in photodynamic therapy treatment of tumors and psoriasis.

Claims

1. A porphycene having the structure ##STR5## wherein each R¹ is, independently, (a) --(CH₂)_n --X, where n=1-4, X is OR² and R² is C_1-6 alkyl, C_6-20 aralkyl or C_6-20 aryl;

CN;

OH;

OCOR² ;

OSO₂ R² ;

NH₂ ;

NHR² ;

N(R²)₂ ;

SH;

SR² ;

S(O)_1-2 R² ;

COOH;

CO₂ R² ;

C(O)NH₂ ;

C(O)NHR² ;

C(O)N(R²)₂ ;

halogen;

or CHO;

(b) --(CH₂)_m CH═

CH₂ where m is 0-2;

or

(c) where one, two or three of the substituents R¹ are C_1-6 alkyl or C_6-20 aryl and the remaining substituents are as above under (a)-(b),

or a pharmaceutically acceptable salt or metal complexes thereof.

2. The porphycene of claim 1, wherein R¹ is --(CH₂)_n --X and X is OR².

3. The porphycene of claim 1, wherein R¹ is --(CH₂)_m CH═

CH₂.

4. The porphycene of claim 1, wherein X is CN, COOH, CO₂ R² or CHO.

5. The porphycene of claim 1, wherein X is OH.

6. The porphycene of claim 1, wherein X is NH₂, NHR², N(R²)₂, C(O)NH₂, C(O)NHR² or C(O)N(R²)₂.

7. The porphycene of claim 1, wherein X is halogen.

8. The porphycene of claim 7, wherein said halogen is bromine.

9. The porphycene of claim 1, wherein X is SH, SR², OSO₂ R², or S(O)_1-2 R².

10. The porphycene of claim 2, wherein R² is methyl.

11. The porphycene of claim 3, wherein m=0.

12. The porphycene of claim 1, wherein at least one R¹ is --(CH₂)_n --OH or --(CH₂)_m --CH═

CH₂.

13. The porphycene of claim 12, wherein one R¹ is --(CH₂)_n --OH or --(CH₂)_m --CH═

CH₂.

14. A pharmaceutical composition comprising a pharmaceutically effective amount of the porphycene of claim 1 and a pharmaceutically acceptable carrier or diluent.

15. The pharmaceutical composition of claim 14, wherein said composition is a solution of said porphycene in water, water-alcohol or dimethyl sulfoxide.

16. The pharmaceutical composition of claim 14, wherein R¹ is --(CH₂)_n --X and X is OR².

17. The pharmaceutical composition of claim 14, wherein R¹ is --(CH₂)_m CH═

CH₂.

18. The pharmaceutical composition of claim 14, wherein R¹ is --(CH₂)_n --X and X is halogen.

19. A method of photodynamic therapy, comprising the steps of:

administering to a mammal in need thereof, an effective amount of the porphycene of claim 1, and

irradiating said mammal with light at a wavelength in the absorption spectrum of said porphycene.

20. The method of claim 19, wherein said administering is topical administration.

21. The method of claim 19, wherein said administering is enteral, parenteral or intramuscular administration.