Compounds and compositions as TLR activity modulators

A method for treating a disease selected from genital warts, actinic keratosis, basal cell carcinoma, human papilloma viral disease, herpes simplex viral disease, cutaneous lymphoma, squamous cell carcinoma and melanoma, wherein the method comprises administering to a subject in need of such treatment an effective amount of a compound of Formula (I-A), or pharmaceutically acceptable salt thereof;

• wherein the compound of Formula (I-A) is
• wherein:
• X3 is N;
• X4 is CR3;
• X5 is —CR4═CR5—;
• R3 is H;
• R4 is H;
• R5 is selected from halogen, —C(O)OR7, —C(O)R7, —C(O)N(R11R12), —N(R11R12), —N(R9)2, —NHN(R9)2, —SR7, —(CH2)nOR7, —(CH2)nR7, -LR10, —OLR8, —OLR10, C1-C6alkyl, C1-C6heteroalkyl, C1-C6haloalkyl, C2-C8alkenyl, C2-C8alkynyl, C1-C6alkoxy, C1-C6haloalkoxy, aryl, heteroaryl, C3-C8cycloalkyl, and C3-C8heterocycloalkyl, wherein the C1-C6alkyl, C1-C6heteroalkyl, C1-C6haloalkyl, C2-C8alkenyl, C2-C8alkynyl, C1-C6alkoxy, C1-C6haloalkoxy, aryl, heteroaryl, C3-C8cycloalkyl, and C3-C8heterocycloalkyl groups of R5 are each optionally substituted with 1 to 3 substituents independently selected from halogen, —CN, —NO2, —R7, —OR8, —C(O)R8, —OC(O)R8, —C(O)OR8, —N(R9)2, —P(O)(OR8)2, —OP(O)(OR8)2, —P(O)(OR10)2, —OP(O)(OR10)2, —C(O)N(R9)2, —S(O)2R8, —S(O)R8, —S(O)2N(R9)2, and —NR9S(O)2R8;
• each L is independently selected from a bond, —(O(CH2)m)t—, C1-C6alkyl, C2-C6alkenylene and C2-C6alkynylene, wherein the C1-C6alkyl, C2-C6alkenylene and C2-C6alkynylene of L are each optionally substituted with 1 to 4 substituents independently selected from halogen, —R8, —OR8, —N(R9)2, —P(O)(OR8)2, —OP(O)(OR8)2, —P(O)(OR10)2, and —OP(O)(OR10)2;
• R7 is selected from C1-C6alkyl, aryl, heteroaryl, C3-C8cycloalkyl, C1-C6heteroalkyl, C1-C6haloalkyl, C2-C8alkenyl, C2-C8alkynyl, C1-C6alkoxy, C1-C6haloalkoxy, and C3-C8heterocycloalkyl, wherein the C1-C6alkyl, aryl, heteroaryl, C3-C8cycloalkyl, C1-C6heteroalkyl, C1-C6haloalkyl, C2-C8alkenyl, C2-C8alkynyl, C1-C6alkoxy, C1-C6haloalkoxy, and C3-C8heterocycloalkyl groups of R7 are each optionally substituted with 1 to 3 R13 groups, and each R13 is independently selected from halogen, —CN, -LR9, -LOR9, —OLR9, -LR10, -LOR10, —OLR10, -LR8, -LOR8, —OLR8, -LSR8, -LSR10, -LC(O)R8, —OLC(O)R8, -LC(O)OR8, -LC(O)R10, -LOC(O)OR8, -LC(O)NR9R11, -LC(O)NR9R8, -LN(R9)2, -LNR9R8, -LNR9R10, -LC(O)N(R9)2, -LS(O)2R8, -LS(O)R8, -LC(O)NR8OH, -LNR9C(O)R8, -LNR9C(O)OR8, -LS(O)2N(R9)2, —OLS(O)2N(R9)2, -LNR9S(O)2R8, -LC(O)NR9LN(R9)2, -LP(O)(OR8)2, -LOP(O)(OR8)2, -LP(O)(OR10)2 and —OLP(O)(OR10)2;
• each R8 is independently selected from H, —CH(R10)2, C1-C8alkyl, C2-C8alkene, C2-C8alkyne, C1-C6haloalkyl, C1-C6alkoxy, C1-C6heteroalkyl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6hydroxyalkyl and C1-C6haloalkoxy, wherein the C1-C8alkyl, C2-C8alkene, C2-C8alkyne, C1-C6heteroalkyl, C1-C6haloalkyl, C1-C6alkoxy, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6hydroxyalkyl and C1-C6haloalkoxy groups of R8 are each optionally substituted with 1 to 3 substituents independently selected from —CN, R11, —OR11, —SR11, —C(O)R11, —OC(O)R11, —C(O)N(R9)2, —C(O)OR11, —NR9C(O)R11, —NR9R10, —NR11R12, —N(R9)2, —OR9, —OR10, —C(O)NR11R12, C(O)NR11OH, —S(O)2R11, —S(O)R11, —S(O)2NR11R12, —NR11S(O)2R11, —P(O)(OR11)2, and —OP(O)(OR11)2;
• each R9 is independently selected from H, —C(O)R8, —C(O)OR8, —C(O)R10, —C(O)OR10, —S(O)2R10, —C1-C6 alkyl, C1-C6 heteroalkyl and C3-C6 cycloalkyl, or each R9 is independently a C1-C6alkyl that together with N they are attached to form a C3-C8heterocycloalkyl, wherein the C3-C8heterocycloalkyl ring optionally contains an additional heteroatom selected from N, O and S, and wherein the C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, or C3-C8heterocycloalkyl groups of R9 are each optionally substituted with 1 to 3 substituents independently selected from —CN, R11, —OR11, —SR11, —C(O)R11, —OC(O)R11, —C(O)OR11, —NR11R12, —C(O)NR11R12, —C(O)NR11OH, —S(O)2R11, —S(O)R11, —S(O)2NR11R12, —NR11S(O)2R11, —P(O)(OR11)2, and —OP(O)(OR11)2;
• each R10 is independently selected from aryl, C3-C8cycloalkyl, C3-C8heterocycloalkyl and heteroaryl, wherein the aryl, C3-C8cycloalkyl, C3-C8heterocycloalkyl and heteroaryl groups are optionally substituted with 1 to 3 substituents selected from halogen, —R8, —OR8, -LR9, -LOR9, —N(R9)2, —NR9C(O)R8, —NR9CO2R8, —CO2R8, —C(O)R8 and —C(O)N(R9)2;
• R11 and R12 are independently selected from H, C1-C6alkyl, C1-C6heteroalkyl, C1-C6haloalkyl, aryl, heteroaryl, C3-C8cycloalkyl, and C3-C8heterocycloalkyl, wherein the C1-C6alkyl, C1-C6heteroalkyl, C1-C6haloalkyl, aryl, heteroaryl, C3-C8cycloalkyl, and C3-C8heterocycloalkyl groups of R11 and R12 are each optionally substituted with 1 to 3 substituents independently selected from halogen, —CN, R8, —OR8, —C(O)R8, —OC(O)R8, —C(O)OR8, —N(R9)2, —NR8C(O)R8, —NR8C(O)OR8, —C(O)N(R9)2, C3-C8heterocycloalkyl, —S(O)2R8, —S(O)2N(R9)2, —NR9S(O)2R8, C1-C6haloalkyl and C1-C6haloalkoxy;
• or R11 and R12 are each independently C1-C6alkyl and taken together with the N atom to which they are attached form an optionally substituted C3-C8heterocycloalkyl ring optionally containing an additional heteroatom selected from N, O and S;
• Ring A is phenyl or pyridyl, wherein the phenyl and pyridyl groups of Ring A are optionally substituted with 1 to 3 RA groups, wherein each RA is independently selected from —R8, —R7, —OR7, —OR8, —R10, —OR10, —SR8, —NO2, —CN, —N(R9)2, —NR9C(O)R8, —NR9C(S)R8, —NR9C(O)N(R9)2, —NR9C(S)N(R9)2, —NR9CO2R8, —NR9NR9C(O)R8, —NR9NR9C(O)N(R9)2, —NR9NR9CO2R8, —C(O)C(O)R8, —C(O)CH2C(O)R8, —CO2R8, —(CH2)nO2R8, —C(O)R8, —C(S)R8, —C(O)N(R9)2, —C(S)N(R9)2, —OC(O)N(R9)2, —OC(O)R8, —C(O)N(OR8)R8, —C(NOR8)R8, —S(O)2R8, —S(O)3R8, —SO2N(R9)2, —S(O)R8, —NR9SO2N(R9)2, —NR9SO2R8, —P(O)(OR8)2, —OP(O)(OR8)2, —P(O)(OR10)2, —OP(O)(OR10)2, —N(OR8)R8, —CH═CHCO2R8, —C(═NH)—N(R9)2, and —(CH2)nNHC(O)R8;
• or two adjacent RA substituents on Ring A form a 5-6 membered ring that contains up to two heteroatoms as ring members;
• n is, independently at each occurrence, 0, 1, 2, 3, 4, 5, 6, 7 or 8;
• each m is independently selected from 1, 2, 3, 4, 5 and 6, and
• t is 1, 2, 3, 4, 5, 6, 7 or 8.