Purine Based Compounds as Toll-Like Receptor 9 Antagonist

1. The compounds can effect and inhibit immune stimulation via TLR9 antagonism.
2. The compounds can be evaluated by medium throughput biological assays involving human peripheral blood mononuclear cells, isolated human primary pDCs and reporter assay using transfected TLR9 cells. The assay system was standardized and the results from all three assay systems can be correlated.
3. The compounds can be used in a number of clinical contexts for treating conditions involving unwanted immune activity in response to a suitable TLR ligand or TLR signaling agonist where inhibition of TLR9 mediated signaling is important such as immunodeficiency, inflammation, infection, sepsis, allergy, asthma, graft rejection, graft-versus host disease (GvHD) and cancer.

The invention relates to the preparation of new compounds in free form or in pharmaceutically acceptable salts form for inhibiting signaling by TLR9. 

The invention relates to small molecules capable of inhibiting immune response mediated through TLR9.

The invention further relates to the preparation of new compounds without considerable cytotoxicity in HepG2 (a hepatic epithelial cell line) and SW480 (an intestinal mucosal epithelial cell line) cells at concentrations below 100 µM.

The invention relates to small molecules capable of inhibiting immune response mediated through TLR9.