Compounds, compositions and methods for prevention and treatment of inflammatory and immunoregulatory disorders and diseases

A compound having the formula (III):

• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• A1 and A4 independently are C(Rb) or N;
• Q is a member selected from the group consisting of a bond, (C1-C8)alkylene, (C2-C8)heteroalkylene, —C(O)—, —OC(O)—, —CH2CO—, —CH2SO— and —CH2SO2—;
• each of W and Y is independently a carbon or a heteroatom and W and Y are linked together to form a 5- or 6-membered cycloalkyl or cycloheteroalkyl ring, wherein the 5- or 6-membered ring is unsubstituted or substituted with halogen, NH2, NO2, (C1-C20)alkyl, (C2-C20)heteroalkyl, heteroaryl, aryl, heteroaryl(C1-C6)alkyl, heteroaryl(C2-C6)heteroalkyl, aryl(C1-C6)alkyl and aryl(C2-C6)heteroalkyl;
• X is —CH2—, SO2 or —C(O)—;
• Ra is selected from the group consisting of —OR′, ═O, ═NR′, ═N—OR′, —NR′R″, —SR′, -halogen, —SiR′R″ R′″, —OC(O)R′, —C(O)R′, —CO2R′, —CONR′R″, —OC(O)NR′R″, —NR″C(O)R′, —NR′—C(O)NR″R′″, —NR″C(O)2R′, —NH—C(NH2)═NH, —NR′C(NH2)═NH, —NH—C(NH2)═NR′, —S(O)R′, —S(O)2R′, —S(O)2NR′R″, —CN and —NO2;
• Rb is selected from the group consisting of —OR′, ═O, ═NR′, ═N—OR′, —NR′R″, —SR′, -halogen, —SiR′R″R′″, —OC(O)R′, —C(O)R′, —CO2R′, —CONR′R″, —OC(O)NR′R″, —NR″C(O)R′, —NR′—C(O)NR″R′″, —NR″C(O)2R′, —NH—C(NH2)═NH, —NR′C(NH2)═NH, —NH—C(NH2)═NR′, —S(O)R′, —S(O)2R′, —S(O)2NR′R″, —CN and —NO2;
• the subscript n is 0, 1, 2 or 3;
• each R′, R″ and R′″ independently is H, unsubstituted (C1-C8)alkyl, heteroalkyl, unsubstituted aryl, or substituted aryl;
• R1 is heteroaryl or aryl;
• R3 is absent or is a member selected from the group consisting of —H, —CHR6R7, —S(O)mR5, —S(O)mN(R8)R9, —S(O)mN(R8)CH2R6, —N(R8)SO2R5, —N(R)CH2R10,
• R4 is a member selected from the group consisting of (C1-C20)alkyl, (C2-C20)heteroalkyl, heteroaryl, aryl, heteroaryl(C1-C6)alkyl, heteroaryl(C2-C6)heteroalkyl, aryl(C1-C6)alkyl and aryl(C2-C6)heteroalkyl;
• R5 is selected from the group consisting of (C1-C8)alkyl, (C2-C8)heteroalkyl, aryl and heteroaryl;
• R6 and R7 independently are hydrogen, (C1-C8)alkyl or (C2-C8)heteroalkyl;
• R8 is hydrogen, (C1-C8)alkyl, (C2-C8)heteroalkyl, heteroaryl or aryl;
• R9 is (C1-C8)alkyl;
• and
• R10 is aryl.

A compound having the formula (IV):

• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• W1 is absent or is selected from the group consisting of —O—, —S—, —S(O)—, —S(O)2—, —C(O)—, —CH2—, or —NR11—;
• W2 and Y independently are —CH2—, —CHR12—, —CH═, —CR12═, —NH—, —N═, or —NR12—;
• W3 is absent or is —O—, —S—, —S(O)—, —S(O)2—, —CH2—, —CHR13—, —CH═, —CR13═, —NH—, —N═, or —NR13—;
• A1 and A4 independently are C(Rb) or N;
• Q is a member selected from the group consisting of a bond, (C1-C8)alkylene, (C2-C8)heteroalkylene, —C(O)—, —OC(O)—, —CH2CO—, —CH2SO— and —CH2SO2—;
• X is —CH2—, SO2 or —C(O)—;
• Ra is selected from the group consisting of —OR′, ═O, ═NR′, ═N—OR′, —NR′R″, —SR′, -halogen, —SiR′R″ R′″, —OC(O)R′, —C(O)R′, —CO2R′, —CONR′R″, —OC(O)NR′R″, —NR″C(O)R′, —NR′—C(O)NR″R′″, —NR″C(O)2R′, —NH—C(NH2)═NH, —NR′C(NH2)═NH, —NH—C(NH2)═NR′, —S(O)R′, —S(O)2R′, —S(O)2NR′R″, —CN and —NO2;
• Rb is selected from the group consisting of —OR′, ═O, ═NR, ═N—OR′, —NR′R″, —SR′, -halogen, —SiR′R″R′″, —OC(O)R′, —C(O)R′, —CO2R′, —CONR′R″, —OC(O)NR′R″, —NR″C(O)R′, —NR″—C(O)NR″R′″, —NR″C(O)2R′, —NH—C(NH2)═NH, —NR′C(NH2)═NH, —NH—C(NH2)═NR′, —S(O)R′, —S(O)2R′, —S(O)2NR′R″, —CN and —NO2;
• the subscript n is 0, 1, 2 or 3;
• each R′, R″ and R′″ independently is H, unsubstituted (C1-C8)alkyl, heteroalkyl, unsubstituted aryl, or substituted aryl;
• R1 is heteroaryl or aryl;
• R3 is absent or is a member selected from the group consisting of —H, —CHR6R7, —S(O)mR5, —S(O)mN(R8)R9, —S(O)mN(R8)CH2R6, —N(R8)SO2R5, —N(R8)CH2R10,
• R4 is a member selected from the group consisting of (C1-C20)alkyl, (C2-C20)heteroalkyl, heteroaryl, aryl, heteroaryl(C1-C6)alkyl, heteroaryl(C2-C6)heteroalkyl, aryl(C1-C6)alkyl and aryl(C2-C6)heteroalkyl;
• R5 is selected from the group consisting of (C1-C8)alkyl, (C2-C8)heteroalkyl, aryl and heteroaryl;
• R and R7 independently are hydrogen, (C1-C8)alkyl or (C2-C8)heteroalkyl,
• R8 is hydrogen, (C1-C8)alkyl, (C2-C8)heteroalkyl, heteroaryl or aryl,
• R9 is (C1-C8)alkyl;
• R10 is aryl;
• R11 is selected from the group consisting of hydrogen, (C1-C8)alkyl, (C2-C8)heteroalkyl, aryl and heteroaryl;
• and
• R12 and R13 are independently (C1-C20)alkyl, (C2-C20)heteroalkyl, heteroaryl, aryl, heteroaryl(C1-C6)alkyl, heteroaryl(C2-C6)heteroalkyl, aryl(C1-C6)alkyl and aryl(C2-C6)heteroalkyl.