Tlr 9 inhibitors

A method of inhibiting TLR9 activity, comprising:

• providing a compound of formula (I), or a pharmaceutically acceptable salt thereof,
• wherein,
• ring B is a substituted monocycle containing 5-6 atoms, the monocycle being selected from a cycloalkyl, aryl, heterocycle or heteroaryl, wherein the heterocycle or heteroaryl has from 1 to 4 heteroatoms that are independently selected from nitrogen, oxygen, and sulfur;
• G represents a substituted or unsubstituted C0-C5 alkylene;
• one of U, W, E and J represents CR-T or N-T and the rest of W, U, E and J independently represent CR2;
• T represents:
• wherein,
• Z is selected from —O—C(O)—, —(O)C—O—, —N—C(O)—, —(O)C—N—, —NH—C(O)—, —(O)C—NH—, —O—C(NCH3)—, —(NCH3)C—O—, —O—C(NR)—, —(NR)C—O—, —O—C(S)—, —(S)C—O—, —C(O)—, —C(O)ON—, and —N—C(O)—O—;
• X represents (—CH2—)n, wherein n=1 to 24, thereby forming an alkylene chain, wherein the carbon atoms of the alkylene chain can be replaced by at least one heteroatom, wherein the heteroatoms are independently —O—, —S— or —NH—, with the proviso that each heteroatom is separated from each other heteroatom by at least one carbon atom, and the alkylene chain is optionally substituted with a halogen, C1-C20 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, halogenated C1-C10 alkyl, hydroxy C1-C10 alkyl, or C1-C10 alkoxy;
• A is at least one ring structure comprised of a cycloalkyl, heterocycle, aryl, heteroaryl or combination thereof that are fused or linked together, which at least one ring structure is unsubstituted or substituted with one or more R groups;
• R1 is one or more of, independently of each other, H, C1-C10 alkyl, halogen, halogenated C1-C10 alkyl, hydroxy C1-C10 alkyl, C1-C10 alkoxy, —CN, amide, or tetrazolyl;
• R2 is one or more of hydrogen or a substituent;
• and
• R is independently hydrogen or a substituent, or two R groups together, if present, form a 3-8 membered saturated or unsaturated carbocyclic or heterocyclic ring which contains at least one heteroatom selected from N, S and O;
• and
• administering the compound to a TLR9 in an amount sufficient to inhibit activity thereof.

A method of treating a disorder or disease, comprising administering a subject in need thereof a compound of formula (I), or a pharmaceutically acceptable salt thereof,

• wherein,
• ring B is a substituted monocycle containing 5-6 atoms, the monocycle being selected from a cycloalkyl, aryl, heterocycle or heteroaryl, wherein the heterocycle or heteroaryl has from 1 to 4 heteroatoms that are independently selected from nitrogen, oxygen, and sulfur;
• G represents a substituted or unsubstituted C0-C5 alkylene;
• one of U, W, E and J represents CR-T or N-T and the rest of W, U, E and J independently represent CR2;
• T represents
• wherein,
• Z is selected from —O—C(O)—, —(O)C—O—, —N—C(O)—, —(O)C—N—, —NH—C(O)—, —(O)C—NH—, —O—C(NCH3)—, —(NCH3)C—O—, —O—C(NR)—, —(NR)C—O—, —O—C(S)—, —(S)C—O—, —C(O)—, —C(O)ON—, and —N—C(O)—O—;
• X represents (—CH2—)n, wherein n=1 to 24, thereby forming an alkylene chain, wherein the carbon atoms of the alkylene chain can be replaced by at least one heteroatom, wherein the heteroatoms are independently —O—, —S— or —NH—, with the proviso that each heteroatom is separated from each other heteroatom by at least one carbon atom, and the alkylene chain is optionally substituted with a halogen, C1-C20 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, halogenated C1-C10 alkyl, hydroxy C1-C10 alkyl, or C1-C10 alkoxy;
• A is at least one ring structure comprised of a cycloalkyl, heterocycle, aryl, heteroaryl or combination thereof that are fused or linked together, which at least one ring structure is unsubstituted or substituted with one or more R groups;
• R1 is one or more of, independently of each other, H, C1-C10 alkyl, halogen, halogenated C1-C10 alkyl, hydroxy C1-C10 alkyl, C1-C10 alkoxy, —CN, amide, or tetrazolyl;
• R2 is one or more of hydrogen or a substituent;
• and
• R is independently hydrogen or a substituent, or two R groups together, if present, form a 3-8 membered saturated or unsaturated carbocyclic or heterocyclic ring which contains at least one heteroatom selected from N, S and O;
• wherein the disorder or disease is antiphospholipid syndrome, autoimmune hepatitis, autoimmune myocarditis, autoimmune orchitis, autoimmune pancreatitis, autoimmune retinopathy, rheumatoid arthritis, psoriatic arthritis, osteoarthritis, systemic Lupus Erythematosus, lupus nephritis, osteoporosis, systemic sclerosis, multiple sclerosis, psoriasis, diabetes, inflammatory bowel disease (Cronh's Disease and Ulcerative Colitis), Hyperimmunoglobulinemia D, periodic fever syndrome, systemic juvenile idiopathic arthritis, sepsis, atherosclerosis, Celiac disease, Sjogren's Syndrome, Alzheimer's disease, Parkinson's disease, or cancer.