Modulators of TLR3/dsRNA complex and uses thereof

Patent metadata

Field	Value
Publication number	US-9409880-B2
Application number	US-201213980874-A
Country	US
Kind code	B2
Filing date	Jan 13, 2012
Priority date	Jan 20, 2011
Publication date	Aug 9, 2016
Grant date	Aug 9, 2016

Abstract

The present invention provides compounds and compositions that can modulate formation of Toll-like receptor 3 (TLR3) and double-stranded RNA (dsRNA) complex, and methods for using the same. In particular, some aspects of the invention provide compounds of the formula:

compositions comprising and methods for using the same, where n, Ar 1 , Ar 2 , X 1 , X 2 , X 3 , Z 1 , and Z 2 are those defined herein.

First claim

What is claimed is:

1. A compound of the formula:

wherein
X 2 is independently —NR a —, —O— or —S—;
each of Z 1 , and Z 2 is independently ═NR a , ═O or ═S;
X 3 is —NR a R b , —OR c , or —SR d ;
each of R 1 , R 2 , R 3 , and R 4 is independently hydrogen, alkyl, —OR c , halide, —NR a R b , or —SR d , provided at least one of R 1 and R 4 is not hydrogen;
each R a is independently hydrogen, alkyl, or a nitrogen protecting group;
R b is hydrogen or alkyl;
each R c is independently hydrogen, alkyl, or a hydroxyl protecting group;
R d is hydrogen, alkyl, or a thiol protecting group.

2. The compound of claim 1 wherein Z 1 and Z 2 are O.

3. The compound of claim 1 , wherein X 2 is NR a .

4. The compound of claim 3 , wherein R a is hydrogen.

5. The compound of claim 1 , wherein X 3 is OR c .

6. The compound of claim 5 , wherein R c is hydrogen.

7. The compound of claim 1 , wherein
R 1 is hydrogen, halide, alkyl, haloalkyl, or —OR c ;
each of R 2 and R 4 is independently hydrogen or halide; and
R 3 is hydrogen, halide, or —OR c , and wherein R e is hydrogen, alkyl, or a hydroxyl protecting group,
provided at least one of R 1 and R 4 is not hydrogen.

8. The compound of claim 7 , wherein R 1 is hydrogen, methyl, trifluoromethyl, Cl, F, or methoxy.

9. The compound of claim 7 , wherein R 2 is hydrogen, F, or Cl.

10. The compound of claim 7 , wherein R 3 is hydrogen, Cl, or OH.

11. The compound of claim 7 , wherein R 4 is hydrogen or F.

12. A composition comprising a compound of claim 1 .

13. A method for inhibiting Toll-like receptor 3 (TLR3)/double-stranded RNA (dsRNA) complex formation comprising contacting a cell with an effective amount of a compound of claim 1 .

Assignees

• Yin Hang
• Cheng Kui
• Univ Colorado Regents

Inventors

• Yin Hang
• Cheng Kui

Classifications

• C07D333/70 Primary

  attached in position 2 · CPC title

• A61K31/381

  having five-membered rings · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• C07C311/19

  to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups · CPC title

• A61K31/404

  Indoles, e.g. pindolol · CPC title