Metal complexes of water soluble texaphyrins

C - Chemistry – Metallurgy – 07 – F

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C07F 5/00 (2006.01) A61K 31/40 (2006.01) A61K 41/00 (2006.01) A61K 49/00 (2006.01) A61K 49/06 (2006.01) A61K 49/08 (2006.01) A61K 51/04 (2006.01) A61L 2/00 (2006.01) C07D 487/22 (2006.01) C07H 15/26 (2006.01) C07H 21/00 (2006.01)

Patent

CA 2127530

The present invention involves water soluble hydroxy-substituted texaphyrins retaining lipophilicity, of formula (I) wherein: M is H, a divalent or a trivalent metal cation; R1, R2, R3, R4 and R5 are independently H, OH, C n H(2n+1)O y or OC n H(2n+1)O y where at least one of R1, R2, R3, R4 and R5 has at least one hydroxy substituent; the molecular weight of any one of R1, R2, R3, R4 or R5 is less than or equal to about 1000 daltons; n is a positive integer or zero; y is zero or a positive integer less than or equal to (2n+ 1); and N is an integer between -20 and +2. These expanded porphyrin-like macrocycles are efficient chelators of divalent and trivalent metal ions. Various metal (e.g., transition, main group, and lanthanide) complexes of the hydroxy-substituted texaphyrin derivatives of the present invention have unusual water solubility and stability. They absorb light strongly in a physiologically important region (i.e. 690-880 nm). They have enhanced relaxivity and therefore are useful in magnetic resonance imaging. They form long-lived triplet states in high yield and act as photosensitizers for the generation of singlet oxygen. Thus, they are useful for inactivation or destruction of human immunodeficiency virus (HIV-1), mononuclear or other cells infected with such virus as well as tumor cells. They are water soluble, yet they retain sufficient lipophilicity so as to have greater affinity for lipid rich areas such as atheroma and tumors. They may be used for magnetic resonance imaging followed by photodynamic tumor therapy in the treatment of atheroma and tumors. These properties, coupled with their high chemical stability and appreciable solubility in water, add to their usefulness.

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