Granted Patent B2

US 11,504,346 · App. 16/200,286 · Granted Nov 22, 2022

Inventors: Elisa Tomat (Tucson, AZ); Tsuhen Chang (Tucson, AZ); Eman A. Akam (Tucson, AZ)

Assignee: ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIVERSITY OF ARIZONA

A61K31/175C07C337/04C07D249/08C07D277/36C07D307/64

Abstract

Claims (43)

1. A redox-activated pro-chelator having a formula according to Formula A-1, Formula A-12, or Formula A-13:

wherein R 1 , R 3 , R 5 , R 7 , R 11 , and R 13 are each independently H, Me, Et, Pr, i-Pr, Ph, alkyl, aryl, heteroaryl, substituted alkyl, substituted aryl, or substituted heteroaryl and R 9 is H, alkyl, aryl, alkoxy, carboxy, hydroxy, amino, phosphate, sulfonate, thiol, nitro, nitrile, or halo;

wherein S is bound to a first carbon on Ar 1 ;

wherein

are bound to another carbon adjacent to the first carbon on Ar 1 ,

wherein m is 0, 1, 2, 3, 4, 5, or 6;

wherein X 1 is O or S;

wherein Ar 1 is aromatic, substituted aromatic, heteroaromatic, substituted heteroaromatic, phenyl, phenol, furan, thiophene, pyrrole, pyridine, imidazole, thiazole, or pyrimidine;

wherein the pro-chelator comprises a disulfide bond; and

wherein Formula A-1 excludes

2. The pro-chelator of claim 1 , wherein the pro-chelator is according to Formula A-2, Formula A-3, Formula A-4, or Formula A-5:

3. The pro-chelator of claim 1 , wherein the pro-chelator is according to Formula A-6, Formula A7, Formula A-8, Formula A-9, Formula A-10 or Formula A-11:

wherein R 31 , R 33 , and R 35 are each independently H, Me, Et, Pr, i-Pr, Ph, alkyl, aryl, alkoxy, carboxy, hydroxy, amino, phosphate, sulfonate, thiol, nitro, nitrile, or halo.

4. The pro-chelator of claim 1 , wherein the pro-chelator is according to Formula A-14, Formula A-25, or Formula A-26:

wherein R 2 , R 4 , R 6 , R 8 , R 12 , and R 14 are each independently H, Me, Et, Pr, i-Pr, Ph, alkyl, aryl, heteroaryl, substituted alkyl, substituted aryl, or substituted heteroaryl and R 10 is H, alkyl, aryl, alkoxy, carboxy, hydroxy, amino, phosphate, sulfonate, thiol, nitro, nitrile, or halo;

wherein n is 0, 1, 2, 3, 4, 5, or 6;

wherein X 2 is O or S; and

wherein Ar 2 is aromatic, substituted aromatic, heteroaromatic, substituted heteroaromatic, phenyl, phenol, furan, thiophene, pyrrole, pyridine, imidazole, thiazole, or pyrimidine.

5. The pro-chelator of claim 4 , wherein the pro-chelator is according to Formula A-15, Formula A-16, Formula A-17, or Formula A-18:

6. The po-chelator of claim 4 , wherein the pro-chelator is according to Formula A19, Formula A-20, Formula A-21, Formula A22, Formula A-23 or Formula A-24:

wherein R 31 , R 32 , R 33 , R 34 , R 35 , and R 36 are each independently H, alkyl, aryl, alkoxy, carboxy, hydroxy, amino, phosphate, sulfonate, thiol, nitro, nitrile, or halo.

7. A redox-activated pro-chelator having a formula according to Formula A-27:

8. The pro-chelator of claim 1 , wherein the pro-chelator is according to Formula A-28:

9. A redox activated pro-chelator having a formula according to Formula B-1, Formula B-2, Formula B-3, or Formula B-4:

wherein R 5 , R 7 , R 9 , R 15 , R 17 , R 19 , R 21 , R 23 , R 25 , R 27 , R 29 , R 37 , R 39 , R 41 , R 43 , R 45 , R 47 , R 49 , R 51 , R 53 , R 55 , R 57 , and R 59 are each independently H, Me, Et, Pr, i-Pr, Ph, alkyl, aryl, heteroaryl, substituted alkyl, substituted aryl, substituted heteroaryl, alkoxy, carboxy, hydroxy, amino, phosphate, sulfonate, thiol, nitro, nitrile, halo, an electron withdrawing group, an ion stabilizing group, or an electron stabilizing goup;

wherein m is 0, 1, 2, 3, 4, 5, or 6; and

wherein Ar 1 is aromatic, substituted aromatic, heteroaromatic, substituted heteroaromatic, phenyl, phenol, furan thiophene, pyrrole, pyridine, imidazole, thiazole, or pyrimidine.

10. The pro-chelator of claim 9 , wherein the pro-chelator is according to Formula B-5:

wherein R 6 , R 8 , R 10 , R 16 , R 18 , R 20 , and R 22 are each independently H, Me, Et, Pr, i-Pr, Ph, alkyl, aryl, heteroaryl, substituted alkyl, substituted aryl, substituted heteroaryl, alkoxy, carboxy, hydroxy, amino, phosphate, sulfonate, thiol, nitro, nitrile, halo, an electron withdrawing group, an ion stabilizing group, or an electron stabilizing group;

wherein n is 0, 1, 2, 3 ,4, 5, or 6; and

wherein Ar 2 is aromatic, substituted aromatic, heteroaromatic, substituted heteroaromatic, phenyl, phenol, furan, thiophene, pyrrole, pyridine, imidazole, thiazole, or pyrimidine.

11. The pro-chelator of claim 9 , wherein the pro-chelator is according to Formula B-6:

wherein R 6 , R 8 , R 10 , R 16 , R 18 , R 24 , R 28 and R 30 are each indpendently H, Me, Et, Pr, i-Pr, Ph, alkyl, aryl, heteroaryl, substituted alkyl, substituted aryl, substituted heteroaryl, alkoxy, carboxy, hydroxy, amino, phosphate, sulfonate, thiol, nitro, nitrile, halo, an electron withdrawing group, an ion stabilizing group, or an electron stabilizing group;

wherein n is 0, 1, 2, 3, 4, 5, or 6; and

wherein Ar 2 is aromatic, substituted aromatic, heteroaromatic, substituted heteroaromatic, phenyl, phenol, furan, thiophene, pyrrole, pyridine, imidazole, thiazole, or pyrimidine.

12. The pro-chelator of claim 9 , wherein the pro-chelator is according to Formula B-7:

wherein R 6 , R 8 , R 10 , R 38 , R 40 , R 42 , R 44 , R 46 and R 48 are each independently H, Me, Et, Pr, i-Pr, Ph, alkyl, aryl, heteroaryl, substituted alkyl, substituted aryl, substituted heteroaryl, alkoxy, carboxy, hydroxy, amino, phosphate, sulfonate, thiol, nitro, nitrile, halo, an electron withdrawing group, an ion stabilizing group, or an electron stabilizing group;

wherein n is 0, 1, 2, 3, 4, 5, or 6; and

wherein Ar 2 is aromatic, substituted aromatic, heteroaromatic, substituted heteroaromatic, phenyl, phenol, furan, thiophene, pyrrole, pyridine, imidazole, thiazole, or pyrimidine.

13. The pro-chelator of claim 9 , wherein the pro-chelator is according to Formula B-8:

wherein R 6 , R 8 , R 10 , R 50 , R 52 , R 54 , R 56 , R 58 and R 60 are each independently H, Me, Et, Pr, i-Pr, Ph, alkyl, aryl, heteroaryl, substituted alkyl, substituted aryl, substituted heteroaryl, alkoxy, carboxy, hydroxy, amino, phosphate, sulfonate, thiol, nitro, nitrile, halo, an electron withdrawing group, an ion stabilizing group, or an electron stabilizing group;

wherein n is 0, 1, 2, 3, 4, 5, or 6; and

wherein Ar 2 is aromatic, substituted aromatic, heteroaromatic, substituted heteroaromatic, phenyl, phenol, furan, thiophene, pyrroe, pyridine, imidazole, thiazole, or pyrimidine.

Assignments (2)

Continuity (8)