Texaphyrins substituted with imidazole are provided

• US 5,969,111 A
• Filed: 02/04/1997
• Issued: 10/19/1999
• Est. Priority Date: 04/14/1994
• Status: Expired due to Fees

• Current Assignee: Pharmacyclics Incorporated (Abbvie Incorporated), Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Pharmacyclics Incorporated (Abbvie Incorporated), Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Kral, Vladimir A., Sessler, Jonathan L., Magda, Darren, Mody, Tarak D., Hemmi, Gregory W.
• Primary Examiner(s): Raymond, Richard L.
• Application Number:
  US08/775,261
• Time in Patent Office: 987 Days
• Field of Search: 540/465, 540/472, 540/145, 534/11, 534/13, 534/15, 534/16, 536/17.1, 536/17.3, 536/17.4, 530/391.3, 530/391.5, 530/345, 530/405
• US Class Current: 534/15
• CPC Class Codes: A61K 41/0038 Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy radiotherapy per se A61N5/10
• 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 47/54 the modifying agent being an organic compound
• CPC Class Codes: A61K 47/546 Porphyrines; Porphyrine with an expanded ring system, e.g. texaphyrine
• CPC Class Codes: A61K 49/0021 the fluorescent group being a small organic molecule
• CPC Class Codes: A61K 51/0485 Porphyrins, texaphyrins wherein the nitrogen atoms forming the central ring system complex the radioactive metal
• CPC Class Codes: B01J 2531/025 Ligands with a porphyrin ring system or analogues thereof, e.g. phthalocyanines, corroles
• CPC Class Codes: B01J 2531/36 Yttrium
• CPC Class Codes: B01J 2531/38 Lanthanides other than lanthanum
• CPC Class Codes: B01J 31/061 Chiral polymers
• CPC Class Codes: B01J 31/1658 immobilised by covalent linkages, i.e. pendant complexes with optional linking groups, e.g. on Wang or Merrifield resins
• CPC Class Codes: B01J 31/1815 with more than one complexing nitrogen atom, e.g. bipyridyl, 2-aminopyridine
• CPC Class Codes: C07D 487/22 in which the condensed system contains four or more 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

Abstract

Texaphyrins substituted with imidazda are provided.

Claims

1. A texaphyrin having the structure:

##STR7## wherein, M is H, a divalent metal cation, or a trivalent metal cation;

each of R₁, R₂, R₃, R₄, R₇ and R₈ is independently hydrogen, hydroxyl, alkyl, hydroxyalkyl, oxyalkyl, oxyhydroxyalkyl, saccharide, oxyaminoalkyl, carboxy, carboxyalkyl, carboxyamidealkyl, a site-directing molecule, imidazole, or a couple to a site-directing molecule or to imidazole, where at least one of R₁, R₂, R₃, R₄, R₇ and R₈ is imidazole or a couple to imidazole; and

N is zero, 1 or 2.

2. The texaphyrin of claim 1 where the metal cation is a divalent metal cation selected from the group consisting of Ca(II), Mn(II), Co(II), Ni(II), Zn(II), Cd(II), Hg(II), Fe(II), Sm(II) and UO₂ (II), or a trivalent metal cation selected from the group consisting of Mn(III), Co(III), Ni(III), Fe(II), Ho(III), Ce(III), Y(III), In(III), Pr(III), Nd)III), Sc(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Er(III), Tm(III), Yb(III), Lu(III), La(III), and U(III).

3. The texaphyrin of claim 1 where R₁ is alkyl or hydroxyalkyl, and each of R₂, R₃ and R₄ is alkyl.

4. The texaphyrin of claim 1 where R₁ is CH₂ CH₂ CH₂ OH, each of R₂ and R₃ is CH₂ CH₃, and R₄ is CH₃.

5. The texaphyrin of claim 1 where R₇ is OCH₂ CH₂ CH₂ OH and R₈ is imidazole, or a couple to imidazole.

6. The texaphyrin of claim 1 where R₇ is O(CH₂ CH₂ O)₂ CH₂ CH₂ OCH₃ and R₈ is imidazole or a couple to imidazole.

7. The texaphyrin of claim 1 where M is a lanthanide metal cation.

8. The texaphyrin of claim 1 where M is a paramagnetic metal cation.

9. The texaphyrin of claim 1 where M is a diarmagnetic metal cation.

10. The texaphyrin of claim 1 where R₁ is CH₂ CH₃ or CH₂ CH₂ CH₂ OH;

each of R₂ and R₃ is CH₂ CH₃ ;

R₄ is CH₃ ;

R₇ is H, CH₃, OCH₃, O(CH₂)_n COOH, OCH₂ CH₂ CH₂ OH or O(CH₂ CH₂ O)_n CH₃ where n is 1-7; and

R₈ is imidazole.

11. The texaphyrin of claim 1 where M is a lanthanide metal cation;

R₁ is CH₂ CH₃ or CH₂ CH₂ CH₂ OH;

each of R₂ and R₃ is CH₂ CH₃ ;

R₄ is CH₃ ;

R₇ is H, CH₃, OCH₃, O(CH₂)_n COOH, OCH₂ CH₂ CH₂ OH or O(CH₂ CH₂ O)_n CH₃ where n is 1-7; and

R₈ is imidazole or a couple to imidazole.

12. The texaphyrin of claim 1 where M is a lanthanide metal cation;

R₁ is CH₂ CH₃ or CH₂ CH₂ CH₂ OH;

each of R₂ and R₃ is CH₂ CH₃ ;

R₄ is CH₃ ;

R₇ is OCH₂ COOH; and

R₈ is imidazole or a couple to imidazole.

13. The texaphyrin of claim 1 where one of R₁, R₂, R₃, R₄, R₇ and R₈ is a site-directing molecule or a couple to a site-directing molecule;

and another of R₁, R₂, R₃, R₄, R₇ and R₈ is imidazole or a couple to imidazole.

14. The texaphyrin of claim 1 where R₇ is a site-directing molecule or a couple to a site-directing molecule;

and R₈ is imidazole or a couple to imidazole.