Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1992-05-07
1993-12-21
Hollrah, Glennon H.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514836, 514908, 534 15, 540145, 435 2, 436 2, A61K 31555, C07F 500, C07D48722
Patent
active
052721426
DESCRIPTION:
BRIEF SUMMARY
R.sub.1R.sub.2.sup.n.spsp.+NN? Cd.sup.+2, Co.sup.+2 or Mn.sup.+2, and n is 1; or M is Ln.sup.+3, Gd.sup.+3, Y.sup.+3 or In.sup.+3 and n is 2; or R.sub.1 is H, R.sub.2 is Cl, Br, NO.sub.2, CO.sub.2 H or OCH.sub.3, M is Zn.sup.+2, Hg.sup.+2, Sn.sup.+2 or Cd.sup.+2 and n is 1.
Absent metal ions, compounds of the present invention may have the structure: ##STR16## or the structure: ##STR17## For example, a method for the synthesis of pentadentate expanded porphyrin compound is an aspect of the present invention. This method comprises synthesizing a diformyl tripyrrane; condensing said tripyrrane with an ortho aryldiamine 1,2-diaminoalkene or 1,2-diaminoalkane; and oxidizing the condensation product to form a pentadentate expanded porphyrin compound. A preferred 1,2-diaminoalkene is diamisomaleonitrile. The ortho aryldiamine is preferably ortho phenylenediamine or a substituted ortho phenylenediamine. Another preferred ortho aryldiamine is 2,3-diaminonapthalene. Such a pentadentate expanded porphyrin compound is complexed with a metal and wherein a metal complex is produced by reaction of the pentadentate expanded porphyrin compound with metal ions.
The present invention also involves a method of deactivating retroviruses and enveloped viruses in blood. This method comprises adding a pentadentate expanded porphyrin analog metal complex as described above to blood and exposing the mixture to light to facilitate the formation of singlet oxygen.
Photodynamic tumor therapy comprising administering a pentadentate expanded porphyrin analog complexed with a metal to a tumor host and irradiating the analog in proximity to the tumor is another aspect of the present invention.
A method for MRI enhancement comprising administering a diamagnetic metal ion (such as gadolinium, for example) complexed with texaphyrin or a texaphyrin derivative is also an aspect of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a schematic structural view of Texaphyrin (1) and various complexes (2, 3 and 4).
FIG. 2 shows a view of complex 4 (from FIG. 1) showing pyridine and macrocycle coordination to Cd. Ellipsoids scaled to the 40% probability level. The Cd ion lies in the plane of the nearly planar macrocycle (maximum deviation from planarity 0.10 (1) .ANG.). Relevant Cd-N bond lengths (.ANG.) are as follows: 2.418(7), N1; 2.268(8), N8; 2.505(7), N13; 2.521(7), N20; 2.248(8), N23; 2.438(14), N1a; 2.473(12), N1b. Selected N-Cd-N bond angles (deg) are as follows: N1-Cd-N8, 78.9(2); N1-Cd-N23, 80.2(3); N8-Cd-N13, 68.4(2); N13-Cd-N20, 64.4(2); N20-Cd-N23, 68.2(3): N1a-Cd-N1b, 176.1(4).
FIG. 3 shows a view of complex 4 perpendicular to the plane through the macrocycle. Pyridine rings (not shown) lie perpendicular to the macrocycle with dihedral angles of 88.5 (4).degree. for ring a and 89.1 (3).degree. for ring b.
FIG. 4 shows a schematic representation of the reduced (1.sub.A) and oxidized (2.sub.A) forms of the free-base "texaphyrin" and representative five, six, and seven coordinate cadmium complexes (3.sub.A -5.sub.A) derived from this "expanded porphyrin".
FIG. 5 shows a view of the cation 5.sub.aA showing pyridine and macrocycle coordination to Cd. Ellipsoids are scaled to the 30% probability level. The cadmium (II) cation lies in the plane of the nearly planar macrocycle (max. deviation from planarity, 0.10(1) .ANG.). Relevant Cd-N bond lengths (.ANG.) are: 2.418(7) N1; 2.268(8) N8; 2.505(7) N13; 2.521(7) N20; 2.248(8) N23; 2.438(14) N1a; 2.473(12) N1b. Selected N-Cd-N bond angles (.degree.) are: 78.9(2) N1-Cd-N8; 80.2(3) N1-Cd-N23; 68.4(2) N8-Cd-N13; 64.4(2) N13-Cd-N20; 68.2(3) N20-Cd-N23; 176.1(4) N1a-Cd-N1b. For further structural details, see ref. 11.
FIG. 6 shows a view of cation 4.sub.bA showing the atom labelling scheme. Thermal ellipsoids are drawn to 30% probability level. Relevant Cd-N bond lengths (.ANG.): N1 2.462(13); N8 2.254(9); N13 2.535(13); N20 2.526(12); N23 2.298(11); N1A 2.310(9). Selected N-Cd-N bond angles (.degree.): N1-Cd-N8 78.3(4); N8-Cd-N13 67.8(4); N13-Cd-N20 64.1(4); N20-Cd-N23 67.3(
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This invention was made in part with government support under the National Science Foundation Presidential Young Investigator Award (1986) to J. L. Sessler, CHE-8552768. The government has certain rights in the invention.
This is a division of copending application Ser. No. 539,975, and issued as U.S. Pat. No. 5,162,509 filed Jun. 18, 1990 which is a division of Ser. No. 320,293 filed Mar. 6, 1989 and issued as U.S. Pat. No. 4,935,498 on Jun. 19, 1990. The copending application and the patent are incorporated by reference herein.
Hemmi Gregory W.
Murai Toshiaki
Sessler Jonathan L.
Board of Regents , The University of Texas System
Hollinden Gary E.
Hollrah Glennon H.
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