Process for preparing expanded porphyrins: large porphyrin-like tripyrroledimethine-derived macrocycles

• US 5,162,509 A
• Filed: 06/18/1990
• Issued: 11/10/1992
• 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): Bond, Robert T.
• Assistant Examiner(s): WARD, EDWARD C
• Application Number:
  US07/539,975
• Time in Patent Office: 876 Days
• Field of Search: 534/11, 534/14, 534/15, 534/16, 540/465, 540/472
• 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 47/546 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

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 physilogically important region (i.e. 690-880 nm). These complexes also form long-lived triplet states in high yield and act as efficient photosensitizers for the formation of singlet oxygen. These properties, coupled with their high chemical stability and appreciable solubility in polar media such as water, add to their usefulness.

Claims

1. A method for synthesizing an aromatic pentadentate expanded porphyrin analog, the method comprising:

mixing, in an organic solvent, a nonaromatic pentadentate expanded porphyrin analog, N,N,N'"'"',N'"'"'-tetramethyl-1,8-diaminonapthalene, an oxygen, air or platinum oxide oxidant; and

a trivalent metal ion selected from the group consisting of cerium, dysprosium, erbium, europium, iron, gadolinium, indium, lutetium, lanthanum, manganese, nickel, neodymium, praseodymium, samarium, thulium, terbium, yttrium, and ytterbium; and

stirring at ambient temperature or heating the mixture at reflux for at least two hours to form an aromatic pentadentate expanded porphyrin analog metal complex.

2. The method of claim 1 wherein the nonaromatic pentadentate expanded porphyrin analog is a condensation product of a diformyl tripyrrane and an ortho phenylenediamine, an ortho napthylenediamine or a 1,2 ethylene diamine.

3. The method of claim 1 wherein the oxidant is air saturating the organic solvent.

4. The method of claim 1 wherein the oxidant is oxygen.

5. The method of claim 1 wherein the oxidant is platinum oxide.

6. The method of claim 1 wherein stirring or heating at reflux step comprises stirring or heating at reflux the mixture for at least 24 hours.

7. The method of claim 1 wherein the organic solution comprises chloroform and methanol.

8. The method of claim 1 wherein the organic solution comprises methanol and benzene.