Aromatic pentadentate expanded porphyrins in magnetic resonance imaging

• US 5,256,399 A
• Filed: 05/07/1992
• Issued: 10/26/1993
• Est. Priority Date: 03/06/1989
• 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., Murai, Toshiaki, Hemmi, Gregory W.
• Primary Examiner(s): Hollrah, Glennon H.
• Assistant Examiner(s): Hollinden, Gary E.
• Application Number:
  US07/880,078
• Time in Patent Office: 537 Days
• Field of Search: 424/9, 436/173, 436/806, 128/653.4, 128/654, 534/15, 540/145, 514/836, 514/185
• US Class Current: 424/9.362
• 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 41/0071 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
• 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: C07D 487/22 in which the condensed system contains four or more hetero rings
• CPC Class Codes: Y10S 436/806 Electrical property or magnetic property
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

The present invention involves a novel tripyrrole dimethine-derived "expanded porphyrin" (texaphyrin), the synthesis of such compounds, their analogs or derivatives and their uses. These expanded porphyrin-like macrocycles are efficient chelators of divalent and trivalent metal ions. Metal complexes of these compounds are active as photosensitizers for the generation of singlet oxygen and thus potentially for inactivation or destruction of human immunodeficiency virus (HIV-1), mononuclear or other cells infected with such virus and tumor cells as well. A variety of texaphyrin derivatives have been produced and many more are readily obtainable. Various metal (e.g., transition, main group, and lanthanide) complexes with the texaphyrin and texaphyrin derivatives of the present invention have unusual water solubility and stability which render them particularly useful. These metallotexaphyrin complexes have optical properties making them unique as compared to existing porphyrin-like or other macrocycles. For example, they absorb light strongly in a physiol

This invention was made in part with government support under the National Science Foundation Presidential Young Investigator Award (1986) to J. L. Sessler, grant CHE-8552768. The government has certain rights in the invention.

Claims

1. A method of magnetic resonance image enhancement comprising administering to a subject an effective amount of a texaphyrin-paramagnetic metal complex.

2. The method of claim 1 wherein the paramagnetic metal is Gd⁺³.

3. A method of detection of neoplastic tissue in a patient comprising:

administering to a patient a texaphyrin-paramagnetic metal complex in an amount effective to enhance a magnetic resonance image; and

detecting neoplastic tissue by magnetic resonance imaging of said patient.

4. The method of claim 3 wherein the paramagnetic metal is Gd⁺³.

5. A method for MRI enhancement comprising administering a diamagnetic metal ion complexed with texaphyrin or a texaphyrin derivative.

6. The method of claim 5 wherein the diamagnetic metal ion is gadolinium.