COMPOUNDS FOR MODULATING T-CELLS

• US 20080293739A1
• Filed: 04/11/2008
• Published: 11/27/2008
• Est. Priority Date: 04/11/2007
• Status: Active Grant

• Current Assignee: University of Utah (State of Utah)
• Original Assignee: University of Utah (State of Utah)
• Inventors: Trede, Nikolaus S.
• Granted Patent: US 8,039,505 B2
• Time in Patent Office: Days
• US Class Current: 514/255.03
• CPC Class Codes: A61K 31/341 not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• CPC Class Codes: A61K 31/421 1,3-Oxazoles, e.g. pemoline, trimethadione
• CPC Class Codes: A61K 31/4402 only substituted in position 2, e.g. pheniramine, bisacodyl
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

Abstract

Disclosed are compounds and compositions that modulate T-cells. Such compounds can be used to treat T-cell mediated disease like T-ALL, rheumatoid arthritis, multiple sclerosis, and graft-vs-host disease (GvHD), to name but a few. The compounds have a general structure as shown in Formula I.

Ar¹-L-Ar²  I

wherein Ar¹ and Ar², are independent of one another, a substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl; and L is a bond or a linker spanning two, three, four, or five atoms.

Claims

1. A method of modulating T-cell activity in a subject diagnosed with a T cell mediated disease, comprising administering to the subject a composition comprising a therapeutic effective amount of a compound having Formula I or a pharmaceutically acceptable salt thereof:

Ar¹-L-Ar² 

 

I

wherein Ar¹ and Ar², are independent of one another, a substituted aryl, unsubstituted aryl, substituted heteroaryl, or unsubstituted heteroaryl; and

L is a bond or a linker spanning two, three, four, or five atoms, and a pharmaceutically acceptable carrier.

2. The method of claim 1, wherein Ar¹ and Ar² are moieties chosen from Formulae IIA, IIB, or IIC.

3. The method of claim 1, wherein L is chosen from methylhydrazine or methylhydrazone.

4. The method of claim 1, wherein L is chosen from methylenepropyl, butyl, pentyl, 1,3 substituted cyclopentyl, 1,3-substituted cyclohexyl, 1,3-substituted cycloheptyl, 1,4-substituted cyclohexyl, 1,4-substituted cycloheptyl, ethyoxyl, propoxyl, butoxyl, methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl, propoxymethyl, methylaminomethyl, methylaminoethyl, methylaminopropyl, ethylaminomethyl, ethylaminoethyl, propylaminomethyl, methoxymethoxymethyl, methoxymethoxyethyl, —

C(O)OCH₂—

, —

C(O)OCH₂CH₂—

, —

C(O)OCH₂CH₂CH₂—

, —

CH₂C(O)O—

, —

CH₂C(O)OCH₂—

, or —

CH₂CH₂C(O)OCH₂—

.

5. The method of claim 1, wherein the compound having Formula I is

6. The method of claim 1, wherein the compound having Formula I is:

7. The method of claim 1, wherein the compound having Formula I is:

8. The method of claim 1, wherein the compound having Formula I is:

9. The method of claim 1, wherein the compound having Formula I is:

10. The method of claim 1, wherein the compound having Formula I is:

11. The method of claim 1, wherein the compound having Formula I is:

12. The method of claim 1, wherein the compound having Formula I is:

13. The method of claim 1, wherein the compound having Formula I is:

14. The method of claim 1, wherein the compound having Formula I is:

15. The method of claim 1, wherein the compound having Formula I is:

16. The method of claim 1, wherein the T-cell mediated disease is acute lymphocytic leukemia.

17. The method of claim 1, wherein the T-cell mediated disease is rheumatoid arthritis.

18. The method of claim 1, wherein the T-cell mediated disease is multiple sclerosis.

19. The method of claim 1, wherein the T-cell mediated disease is graft-vs-host disease (GvHD).

20. The method of claim 1, wherein the composition is administered prior to treatment with an approved chemotherapeutic agent.