Purine derivatives and their use for treatment of autoimmune diseases
Compounds useful in the treatment of autoimmune disease are described by the following general formula: n=0-2 m=0-2 m is not necessarily equal to n; where R 1 , R 3 ═NH 2 , F, Cl, C 1 -C 4 alkoxy or phenoxy group, but R 1 is not necessarily equal to R 3 ; and R 2 ═H, F, Cl, NH 2 , or NH—R—XH;
1. A compound of the following formula:
n =0-2
m =0-2
m is not necessarily equal to n;
where:
R 1 is NH 2 ;
R 3 is NH 2 , F, or Cl; and
R 2 is H, F, Cl, NH 2 , or NH—R—XH;
or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , wherein R 1 =NH 2 ; R 3 =NH 2 , F, or Cl; n=0; and m=2.
3. The compound according to claim 1 , wherein R 1 =meta-NH 2 ; R 3 =meta-NH 2 , F, or Cl; R 2 =H; n=0; and m=2.
4. A compound selected from the group consisting of:
Com-
pound
No.
Structure
1
2
3
4
5
6
7
8
10
11
12
13
and
14
or a pharmaceutically acceptable salt thereof.
5. The compound according to claim 1 , wherein said compound is capable of noncovalently binding to the Fc portion of a human IgG antibody.
6. A composition comprising at least one compound according to claim 1 and a pharmaceutically acceptable carrier.
7. The composition according to claim 6 further comprising a recombinant protein which binds to human TNFα.
8. The composition according to claim 6 further comprising methotrexate, an anti-inflammatory corticosteroid, a nonsteroidal anti-inflammatory drug, or a combination thereof.
9. A method for isolating an antibody or an antibody-antigen immune complex, comprising binding a compound of claim 1 to an antibody or an antibody-antigen immune complex and separating unbound material to isolate said antibody or antibody-antigen immune complex.
10. The method of claim 9 , wherein said compound is immobilized to an insoluble support.
11. A method of reducing and/or alleviating synovitis in a patient with rheumatoid arthritis or psoriatic arthritis, comprising administering to said patient a therapeutically effective amount of a compound according to claim 1 .
12. The method of claim 9 , wherein the said compound is covalently linked to a support selected from the group consisting of a glass slide, a multiwell plate, an optical fiber, a protein chip, a test tube, a tissue culture dish, a magnetic beads, a porous membrane or a chromatographic media.
13. The method of claim 9 , wherein said antibody is an IgM, an IgD, an IgA1, an IgA2, an IgE, an IgG1, an IgG2, an IgG3, an IgG4, and and/or an Fc-containing material.
14. The method of claim 10 , wherein said insoluble support is made of a material selected from the group consisting of agarose, dextran, cellulose, polyacrylamide, silica, and glass.
15. A method of reducing and/or alleviating synovitis in a patient with systemic lupus erythematosus, comprising administering to said patient a therapeutically effective amount of a compound according to claim 1 .