Desazadesferrothiocin and desazadesferrothiocin polyether analogues as metal chelation agents

• US 9,045,440 B2
• Filed: 05/04/2011
• Issued: 06/02/2015
• Est. Priority Date: 05/04/2010
• Status: Expired due to Fees

• Current Assignee: Ferrokin Biosciences Incorporated (Shire plc)
• Original Assignee: Ferrokin Biosciences Incorporated (Shire plc)
• Inventors: Malecha, James
• Primary Examiner(s): Otton, Alicia L
• Application Number:
  US13/100,705
• Publication Number:
  US 20110275636A1
• Time in Patent Office: 1,490 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 39/04 Chelating agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07D 231/14 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 233/28 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 263/16 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 277/12 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 277/56 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

Abstract

Disclosed herein are new compounds of desazadesferrothiocin polyether (DADFT-PE) analogs, as well as pharmaceutical compositions comprising them and their application as metal chelation agents for the treatment of disease. Methods of chelation of iron and other metals in a human or animal subject are also provided for the treatment of metal overload and toxicity.

Claims

1. A compound having a structural formula chosen from the group consisting of IIIa, IIIb, IIIc and IIId:

2. The compound as recited in claim 1, having a structural formula chosen from the group consisting of IIIa1, IIIa2, IIIa3, IIIb1, IIIb2, IIIb3, IIIc1, IIIc2, IIIc3, IIId1, IIId2, and IIId3:

3. The compound as recited in claim 2, wherein Z is OR₁.

4. The compound as recited in claim 3, wherein R₁ is [(CH₂)_m—

O]_x—

[(CH₂)_x—

O]_y—

R₄.

5. The compound as recited in claim 4, wherein:

each m and each n is, independently, an integer from 1 to 4;

x is an integer from 0 to 4; and

y is an integer from 1 to 4.

6. The compound as recited in claim 5, wherein R₄ is alkyl.

7. The compound as recited in claim 6, wherein:

each n is, independently, an integer from 2 to 3;

x is 0; and

y is an integer from 1 to 4.

8. The compound as recited in claim 7, wherein R₄ is lower alkyl.

9. The compound as recited in claim 8, wherein R₇ is OR₈.

10. The compound as recited in claim 9, wherein:

each n is 2;

x is 0;

y is an integer from 2 to 3; and

R₄ is methyl.

11. The compound as recited in claim 10, wherein R₈ is hydrogen.

14. A pharmaceutical composition comprising the compound as recited in claim 1, together with at least one pharmaceutically acceptable excipient.

12. A compound selected from the group consisting of:

13. The compound as recited in claim 12, chosen from: