Derivatized corroles and metallocorroles and their use as imaging and therapeutic agents

Patent metadata

Field	Value
Publication number	US-10035806-B2
Application number	US-201615286983-A
Country	US
Kind code	B2
Filing date	Oct 6, 2016
Priority date	Oct 6, 2015
Publication date	Jul 31, 2018
Grant date	Jul 31, 2018

Abstract

The present invention is directed to derivatized corroles, methods of making and using the same as imaging and therapeutic agents. In certain embodiments, the corroles are compounds having a Structure (I-H) and (I-M):

where R 1 , R 2 , R 3 , and R 4 are independently —F or —N(H)—(CH 2 ) m —Y, provided that at least one of R 1 , R 2 , R 3 , and R 4 is —N(H)—(CH 2 ) m —Y, and m and Y are described herein.

First claim

What is claimed:

1. A compound of Formula (I-M):

wherein
R 1 , R 2 , and R 3 are independently —F or —N(H)—(CH 2 ) m —Y, provided that at least one of R 1 , R 2 , or R 3 is —N(H)—(CH 2 ) m —Y;
—Y is —N(Z) 2 , —O—Z, —C(O)—O—Z, —OC(O)Z—, —OC(O)O—Z, —C(O)N(Z) 2 , —NH—C(O)—Z, —C(O)NHNH—Z
—Z is independently R 5 , —(CH 2 ) m —X, —(CH 2 ) m —OR 5 , —(CH 2 ) m —SR 5 , —(CH 2 ) m —N(R 5 ) 2 , —(CH 2 CH 2 O) n —OR 5 , —(CH 2 CH 2 O) n —N(R 5 ) 2 , —(CH 2 ) m —N 3 , —(CH 2 ) m —C≡C—R 5 , an amino acid, peptide, protein, polyol;
R 5 is independently H or C 1-12 alkyl;
X is Cl, Br, or I;
m is independently 1-18;
n is 1-32; and
M is Ag, Al, Co, Cr, Cu, Fe, Ga, Ge, Hf, Ir, Mo, Mn, Nb, Ni, Os, Pt, Re, Rh, Ru, Sb, Sn, Ta, Ti, V, or W, a lanthanide or actinide, or an isotope or radionuclide thereof, each of which is optionally coordinated to one or more ligands.

2. The compound of claim 1 , having a Formula (I-M), where M is Al, Cr, Co, Fe, Ga, Mn, Rh, Ru, or Sn having 0, 1, or 2 axial nitrogen donor ligands.

3. The compound of claim 1 , having a Formula (I-M), where M is Co, Cr, Fe, Ga, Ir, Mn, Rh, Ru, or Sn having 0, 1, or 2 axial phosphine ligands.

4. The compound of claim 1 , having a Formula (I-M), where M is Al or Ga, optionally coordinated to one or more ligands.

5. The compound of claim 1 , having a Formula (I-M), where M is Ga(III) having 0, 1, or 2 axial tertiary or aromatic amine ligands.

6. The compound of claim 1 , having a Formula (I-M), where M is Ga(III) having 0, 1, or 2 axial pyridine ligands.

7. The compound of any one of claims 1 to 6 , wherein two or three of R 1 , R 2 , or R 3 are —N(H)—(CH 2 ) m —Y.

8. A pharmaceutical composition comprising a pharmaceutically acceptable inert ingredient and a compound of claim 1 .

9. The pharmaceutical composition of claim 8 , wherein the composition is in a form suitable for local or systemic administration.

10. The pharmaceutical composition of claim 8 or claim 9 having a Formula (I-M), where M is Al or Ga, optionally coordinated to one or more ligands.

11. The pharmaceutical composition of claim 8 or claim 9 , having a Formula (I-M), where M is Ga(III) having 0, 1, or 2 axial tertiary or aromatic amine ligands.

12. The pharmaceutical composition of claim 8 or claim 9 , having a Formula (I-M), where M is Ga(III) having 0, 1, or 2 axial pyridine ligands.

13. A method of preparing a compound of claim 1 , comprising reacting a compound of Formula (I-H), with a precursor compound or salt of Ag, Al, Co, Cr, Cu, Fe, Ga, Ge, Hf, Ir, Mo, Mn, Nb, Ni, Os, Pt, Re, Rh, Ru, Sb, Sn, Ta, Ti, V, W, a lanthanide or actinide, or an isotope or radionuclide thereof, under conditions to produce a compound of Formula (I-M), so as to produce the compound of Formula (I-M)

wherein M is Ag, Al, Co, Cr, Cu, Fe, Ga, Ge, Hf, Ir, Mo, Mn, Nb, Ni, Os, Pt, Re, Rh, Ru, Sb, Sn, Ta, Ti, V, W, a lanthanide or actinide, or an isotope or radionuclide thereof, each of which is optionally coordinated to one or more ligands.

14. The compound of claim 1 , where M is Ga(III) having one axial pyridine ligand.

15. The pharmaceutical composition of claim 8 or claim 9 , where M is Ga(III) having one axial pyridine ligand.

Assignees

• California Inst Of Techn

Inventors

• Yen Melanie A
• Gray Harry B
• Grubbs Robert H
• PALMER Joshua

Classifications

• C07F5/003

  without C-Metal linkages · CPC title

• C07D487/22 Primary

  in which the condensed system contains four or more hetero rings · CPC title