Water-soluble sapphyrins

• US 5,543,514 A
• Filed: 04/06/1995
• Issued: 08/06/1996
• Est. Priority Date: 12/21/1989
• Status: Expired due to Term

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Sessler, Jonathan L., Kral, Vladimir
• Primary Examiner(s): Shah, Mukund J.
• Assistant Examiner(s): Sripada, Pavanaram K.
• Application Number:
  US08/417,940
• Time in Patent Office: 488 Days
• Field of Search: 540/472, 540/145, 536/123.1, 536/20, 536/3, 536/112
• US Class Current: 540/472
• CPC Class Codes: A61K 41/0076 PDT with expanded (metallo)porphyrins, i.e. having more than 20 ring atoms, e.g. texaphyrins, sapphyrins, hexaphyrins, pentaphyrins, porphocyanines
• CPC Class Codes: A61K 47/546 Porphyrines; Porphyrine with an expanded ring system, e.g. texaphyrine
• CPC Class Codes: A61K 47/558 the modifying agent being a chemiluminescent acceptor
• CPC Class Codes: C07D 487/22 in which the condensed system contains four or more hetero rings
• CPC Class Codes: C07H 15/26 Acyclic or carbocyclic radicals, substituted by hetero rings
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12N 15/101 by chromatography, e.g. electrophoresis, ion-exchange, reverse phase

Abstract

Sapphyrins are provided having appended functional groups that render the sapphyrin water-soluble. Such water-soluble sapphyrins are useful for photodynamic therapy, for example.

Claims

1. A water-soluble sapphyrin having structure II:

##STR20## wherein each of R¹ -R¹⁰ are independently hydrogen, alkyl, alkene, alkyne, halide, alkylhalide, hydroxyalkyl, hydroxyalkylamido, glycol, polyglycol, thiol, thioalkyl, aminoalkyl, carboxyalkyl, carboxyamidealkyl, oxyalkyl, alkoxyalkyl, aryloxyalkyl, oxyhydroxyalkyl, alkyloxycarbonyl, aryloxycarbonyl, aldehyde, ether, ketone, carboxylic acid, phosphate, phosphonate, sulfate, phosphate substituted alkyl, phosphonate substituted alkyl, or sulfate substituted alkyl, such that the total number of carbon atoms in each substituent R is less than or equal to 100;

wherein at least one of R¹ -R¹⁰ is of the formula (CH₂)_n --A--(CH₂)_m --B, where

A is alkyl having from 1-4 carbon atoms, oxy, sulfide, amide, carbonyl, alkenyl, alkynyl, alkylhalide, hydroxyalkyl, glycol, polyglycol, alkylthiol, substituted alkyl, phosphate, phosphonate, sulfate, phosphate substituted alkyl, phosphonate substituted alkyl, sulfate substituted alkyl, carboxy, carboxyamide, ester, thiol-substituted carboxyamide, or derivatized carboxyamide;

B is hydroxy, hydroxyalkyl, oxyalkyl, carboxy, carboxyalkyl, glycol, polyglycol, thiol, aminoalkyl, phosphate, phosphonate, sulfate, phosphate substituted alkyl, phosphonate substituted alkyl, sulfate substituted alkyl, substituted hydroxyalkyl, saccharide, saccharide derivative, or polysaccharide; and

n and m are independently an integer from 0 to 4.

2. The water-soluble sapphyrin of claim 1, wherein

A is alkyl having 1-4 carbon atoms, oxy, sulfide, amide, carbonyl, carboxy, carboxyamide, ester, thiol-substituted carboxyamide, or derivatized carboxyamide;

and

B is hydroxy, hydroxyalkyl, saccharide, saccharide derivative or polysaccharide.

3. The water-soluble sapphyrin of claim 1, wherein B is hydroxyalkyl.

4. The water-soluble sapphyrin of claim 3 wherein the hydroxyalkyl is hydroxymethyl, hydroxyethyl, hydroxypropyl, or hydroxybutyl.

5. The water-soluble sapphyrin of claim 1 wherein A is carboxyamide and B is hydroxyalkyl.

6. The water-soluble sapphyrin of claim 1 wherein A is oxy and B is oxyalkyl.

7. The water-soluble sapphyrin of claim 1 wherein A is alkenyl and B is hydroxy.

8. The water-soluble sapphyrin of claim 1 wherein A is carboxyamide and B is saccharide.

9. The water-soluble sapphyrin of claim 1, further defined as having substituents R², R⁴ -R⁷ and R⁹ as set forth in Table 2 or 3.

10. The water-soluble sapphyrin of claim 2, where B is saccharide or saccharide derivative.

11. The water-soluble sapphyrin of claim 10, wherein the saccharide or saccharide derivative is selected from those set forth in Table 1.

12. The water-soluble sapphyrin of claim 1, where B is a polysaccharide.

13. The water-soluble sapphyrin of claim 12, where the polysaccharide is chitosan, alginic acid, hyaluronic acid or dextran.

14. The water-soluble sapphyrin of claim 1, wherein R⁵ is of the formula (CH₂)_n --A--(CH₂)_m --B, where B is hydroxyalkyl or saccharide.

15. The water-soluble sapphyrin of claim 14 wherein B is saccharide and the saccharide is D-glucose, D-mannose, L-mannose, or D-galactose.

16. The water-soluble sapphyrin of claim 1, wherein R⁴ is of the formula (CH₂)_n --A--(CH₂)_m --B, where B is hydroxyalkyl or saccharide.

17. The water-soluble sapphyrin of claim 1, wherein R⁷ is of the formula (CH₂)_n --A--(CH₂)_m --B, where B is hydroxyalkyl or saccharide.

18. The water-soluble sapphyrin of claim 1, wherein R⁵ is of the formula (CH₂)_n --A--(CH₂)_m --B, where B is carboxyalkyl.

19. The water-soluble sapphyrin of claim 1, wherein R⁷ is of the formula (CH₂)_n --A--(CH₂)_m --B, where B is carboxyalkyl.

20. A water-soluble sapphyrin selected from sapphyrins A1-A27 of Table 2 or B1-B8 of Table 3.