E BIS-[N-((5-CARBAMOYL)-1HBENZO[D]IMIDAZOLE-2-YL)-PYRAZOLE-5-CARBOXAMIDE] AS STING (INTERFERON GENE STIMULATOR) AGONISTS FOR CANCER TREATMENT

Abstract

The present invention relates to compounds of formula (IA') as STING (interferon gene stimulator) agonists for use in the treatment of, for example, cancer, obesity, liver injury, lipid and glucose metabolism disorders, and viral infections. The present invention discloses the synthesis and characterization of exemplary compounds, as well as their pharmacological data (for example, pages 128 to 286: examples 1 to 54; tables 1, 2a, 2b, and 3). An exemplary compound is, for instance, example 1: (E)-N-(5-carbamoyl-1-(4-(5-carbamoyl-2-(4-ethyl-2-methyloxazol-5-carboxamido)-7-(3-hydroxypropoxy)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl)-7-methoxy-1H-benzo[d]imidazol-2-yl)-4-ethyl-2-methyloxazol-5-carboxamide (compound 9).

Description

DERIVED AND RELATED COMPOUNDS OF BIS-rN-((5-CARBAMOIL)-1HBENZOrDllMIDAZOL-2-YL)-PYRAZOL-5-CARBOXAMIDAl AS STING (INTERFERN GENE STIMULATOR) AGONISTS FOR THE TREATMENT OF CANCER Related requests This application claims the priority and benefit of the U.S. Provisional Application. No. 62 / 882,081, filed August 2, 2019, Provisional Application U.S. No. 62 / 944,643, filed December 6, 2019, and Provisional Application U.S. No. 62 / 982,935, filed February 28, 2020. The contents of each of these applications are incorporated herein by reference in their entirety. Background The Stimulator of Inferred Genes (STING) is a receptor in the endoplasmic reticulum that propagates detection in the innate immune system of pathogen-derived cytosolic and self-DNA. STING is a 378 amino acid protein, which contains mainly three structural domains: (i) N-terminal transmembrane domain (aa 1-154); (i) central globular domain (aa 155-341); and (iii) C-terminal tail (aa 342-379). The STING protein can form symmetric dimers combined with its ligands in a V-shaped conformation, without completely covering the bound ligands. A STING agonist can bind in the pocket region of STING. However, the STING activation process is easily inhibited in some severe diseases, resulting in inactivation of the STING pathway. Therefore, the screening and design of potent STING agonists is of great importance for cancer immunotherapy and other infectious disease treatments, including but not limited to obesity, liver injury, lipid-sugar metabolism. , and virus infection. Specific targeting of immune pathways presents opportunities for cancer therapy, potentially offering greater specificity than cell population-based therapeutic approaches. The compounds of this invention modulate the activity of STING and, consequently, may provide a beneficial therapeutic impact in the treatment of diseases, disorders and / or conditions in which the modulation of STING (stimulator of interferon genes) is beneficial, including , but not limited to, inflammation, allergic and autoimmune diseases, infectious diseases, cancer, pre-cancerous syndromes, and as vaccine adjuvants. Brief description of the invention In some aspects, the present invention provides a compound of Formula (lAj LCQfrzn / zznz / q / viAi R14 LCQfrzn / zznz / q / viAi (lAj or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Wi,Xi, Yi, Zi, W2, X2, Y2, and Z2 are, each independently, OR , S, C, or N; X3 and X4 are, each independently, S or NRf; Xs is N or CRA2; X6es N or CRA1; X9is N or CR4; r and s are, each independently, 0 or 1; p is 1 or 2; the total of r and s is 1 or 2; RA1 and ra2 are cac|a a0 independently, H, halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, O-P(O)(OH)2, -O-P(O)(R'R)2, -N( Re)(Rf), -CO2Rf, -N(Rf)CORb, -N(R9)SO2(Ci-4 alkylj-NÍR^ÍR1), N(R9)CO(Ci-4 alkyl)-N(Rh)( Rf), (Cvb alkyl) optionally substituted, (Cvb alkyl)oxy- optionally substituted, (C1-6 alkyl)amino- optionally substituted, and (C1-3 alkyl)(Ci-4 alkyl)amino- optionally substituted, where the (C1-6 alkyl) of said (C1-6 alkyl) optionally substituted, (C1-6 alkyl)oxy-optionally substituted, (Ci-b alkyl)amino-optionally substituted and (C1-6 alkyl)(Ci-4 optionally substituted alkyl)amino is optionally substituted with 1-4 substituents, each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(R R)2, C1-4 alkoxy-, -N(Re )(R*), COz / Rj, -CON(R«)(Rf), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-PfOXR'R^ amino, (Ci-ealkyl)amino-, (C1-6 alkyl )(Ci-e alkyl)amino, -(C1-6 alkyl)-NH2, halo(Ci-e alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)( OH)2, -(C1-4 alkyl)-OP(O)(R'R)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -( C2-4alkoxy)-0-P(0)(OH)2, -(C2-4alkoxy)-OP(O)(R'R)2, -C1-4alkyl-(Ci-4alkoxy), and C1 -4 alkoxy-(Ci-4 alkoxy)-; when r is 0, RB1 and RB2 are, each independently, H, Ci-e optionally substituted alkyl, halo(Ci-e alkyl), C2-6 optionally substituted alkenyl, C2-6 optionally substituted alkynyl, C3-6 optionally substituted cycloalkyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 910 membered heteroaryl, wherein said Cí e optionally substituted alkyl, Cz-e optionally substituted alkenyl, Cz-e alkynyl optionally substituted, C36 optionally substituted cycloalkyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, nitro, -Rc, OH, -O-P(O)(OH)2, -Ο-Ρ(Ο)(Ρ'Ρ)2 -ORg, -NH2, -NRcRc, -NRGRd, -OCORC, - CO2H, -CO2RC, -SORC, -SO2RC, -CONH2, -CONRGRd, -SO2NH2, -SO2NRGRd, -OCONH2, -OCONRGRd, -NRdCORG, -NRdSORG, -NRdCO2RG, and -NRdSOzRG; when s is 0, RC1 is absent, or is H, halogen, or C1-4 alkyl and RC2 is absent or is optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl group is optionally substituted with a substituent selected from - ORG, -NRGRd, -CO2RG, -CONRGRd, SO2NRGRd, and -OCONRcRd; when r is 1, RB1 and RB2 are, each independently, -CH2-, and B, taken together with RB1 and RB2, forms a linking group, where B is a bond or B is -halo(Ci-w alkyl)-, -C1-10 alkyl optionally substituted, -C2-10 alkenyl- optionally substituted, -C2-10 alkynyl- optionally substituted, -C1-6 alkyl-O-Ci-6 alkyl- optionally substituted, -C1-6 alkyl-NRa-Ci -6 alkyl- optionally substituted, C3-6 cycloalkyl optionally substituted, phenyl optionally substituted, 4-6 membered heterocycloalkyl optionally substituted, 5-6 membered heteroaryl optionally substituted, -C1-4 alkyl(C3-6 cycloalkyl)- Ci-4 alkyl- optionally substituted, -C1-4 alkyl-phenyl-Ci-4 alkyl- optionally substituted, -C1-4 alkyl-(4-6 membered heterocycloalkyl)-Ci-4 alkyl- optionally substituted, or -C1 -4 alkyl-(5-6 membered heteroaryl)-Ci 4 alkyl- optionally substituted, wherein the alkyl moiety of said -C1-10 alkyl- optionally substituted, -C2-10 alkenyloptionally substituted, -C2-10 alkynyl- optionally substituted, -C1-6 alkyl-O-Ci-6 alkyl optionally substituted, -C1-6 alkyl-NRa-Ci-e alkyl- optionally substituted, -C1-4 alkyl-(C3-6 cycloalkyl)-Ci-4 alkyl- optionally substituted, -C1-4 alkyl-phenyl-Ci-4 alkyl- optionally substituted, C1-4 alkyl-(4-6 membered heterocycloalkyl)-Ci-4 alkyl- optionally substituted, or -C1-4 alkyl(heteroaryl 5-6 members -Ci-4 alkyl)- optionally substituted is optionally substituted with 1 or 2 substituents, each independently selected from halogen, halo(Ci-4 alkyl), -OH, -OP(O)(OH)2, -O-P(O)(R'R)2, -ORg, -NH2, -NRcRd, -OCORG, -CO2H, -CO2RG, -SORG, -SO2RG, -CONH2, CONRGRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRGRd, -NRdCORc, -NRdSORG, -NRdCO2RG, and NRdSO2RG, and the C3-6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said optionally substituted C3-6cycloalkyl, optionally substituted phenyl , heterocycloalkyl of 4 LCQfrzn / zznz / q / YiAi members optionally substituted, 5-6 membered heteroaryl optionally substituted, -C1-4 alkyl(C3-6 cycloalkyl)-Ci-4 alkyl- optionally substituted, -C1-4 alkyl-phenyl-Ci- 4 alkyl- optionally substituted, -C1-4 alkyl-(4-6 membered heterocycloalkyl)-Ci-4 alkyl- optionally substituted, or -C1-4 alkyl-(5-6 membered heteroaryl)-Ci-4 alkyl- optionally substituted is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -OP(O)(OH)z, -O-P(O)(OR'R)2, amino, (Ci-4alkyl)amino -, (C1-4 alkyl)(Ci-4 alkyl)amino-, C14 alkyl, halo(Ci4 alkyl), halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2 4 alkoxy)-, -(C2 4 alkoxy)-0-P(0)(OH)2, -(C2 4 alkoxy)-OΡ(Ο)(Ρ'Ρ)2, and C1-4 alkoxy-(Ci-4 alkoxy)-; when s is 1, W1 and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D taken together with RC1 and RC2 forms a linking group, where D is halo(Ci -i2alkyl)-, -C1-12alkyl- optionally substituted, -C2-i2alkenyl- optionally substituted, -C2-12alkynyl- optionally substituted, -Ci-β alkyl-O-Ci-6alkyl- optionally substituted, -C1- 6 alkyl-NRa-Ci6 alkyl- optionally substituted, -C1-6 alkyl-(C3-6cycloalkyl)-Ci-6 alkyl- optionally substituted, -C1-6 alkyl-phenyl-Ci-6 alkyl- optionally substituted, -C1- 6 alkyl-(4-6 membered heterocycloalkyl)-Ci-6 alkyl- optionally substituted, or -C1-6 alkyl-(5-6 membered heteroaryl)-Ci-6 alkyl- optionally substituted, wherein the alkyl moiety of said -C1-12 alkyl- optionally substituted, -C1-6 alkenyloptionally substituted, -C2-12 alkynyl- optionally substituted, -Ci-e alkyl-O-Ci-6 alkyloptionally substituted, -Ci-β alkyl-NRa-Ci- 6 alkyl- optionally substituted, -C1-6 alkyl-(C3-6 cycloalkyl)-Ci-6 alkyl- optionally substituted, -C1-6 alkyl-phenyl-Ci-6 alkyl- optionally substituted, C1-6 alkyl-(heterocycloalkyl 4-6 membered)-Ci-6 alkyl- optionally substituted, or -C1-6 alkyl(5-6 membered heteroaryl)Ci-6 alkyl- optionally substituted is optionally substituted with 1 or 2 substituents, each independently selected from halogen, halo(Ci-4 alkyl), -OH, -OP(O)(OH)2, -O-P(O)(R'R)2, -ORc, -NH2, -NRcRd, -OCORC, -CO2H, -CO2RC, -SORC, -SO2RC, -CONH2, CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and NRdSO2Rc, and the remainder C3-6Cícloalkyl, phenyl, heterocycloalkyl 4-6 membered, or 5-6 membered heteroaryl of said -C1-6 alkyl-(C3-6 cycloalkyl)-Ci-6 alkyl- optionally substituted, -C1-6 alkyl-phenyl-Ci-6 alkyloptionally substituted, -C1-6 alkyl-(4-6 membered heterocycloalkyl)-Ci-6 alkyl- optionally substituted, or -Ci-e alkyl-(5-6 membered heteroaryl)-Ci-6 alkyl- optionally substituted is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, O-P(O)(R'R)2, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino, C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-OP(O)(OH)2, -(θ2-4 3ΐοοχί)-Ο-Ρ(Ο)(Ρ'Ρ)2, and C1-4 alkoxy-(Ci-4 alkoxy) -; R3 and R5 are, each independently, -CON(Rd)(Rj, -CH2N(Rd)(Rf), -N(Rd)(R*), -N(Rd)CO(Rf), -ΟΗ2Ν(Ρό)ΟΟ (Ρί), or one of R3and R5es -CON(Rd)(Rf), -CH2N(Rd)(Rf), -N(Rd)(Rf), -NÍR^COÍR1), or -CH2N(Rd)CO( R1), and the other of R3 and R5 is H, COOH, or -CO2RC; LCQfrzn / zznz / q / viAi R4 and R6 are selected, each independently, from H, halogen, halo(Ci-6 alkyl), halo(Ci-6 alkoxy)-, hydroxyl, -O-P(O)(OH)2, O-P(O)(R'R )2, -NH2, -NRCRC, -NRcRd, -CORC, -CO2RC, N(Rd)CORc, -N(Rd)SO2Rc, -N(R9)SO2(Ci-2alkylj-NCR^CR1), -N( R9)CO(Ci-2 alkyl)-N(Rh)(Rf), (Ci-6 alkyl) optionally substituted, (C1-6 alkyl)ox¡- optionally substituted, (C1-6 alkyl)amino- optionally substituted, and (C1-6 alkyl)(Ci-4 alkyl)amino-optionally substituted, wherein the (Ci-e alkyl) of said (Cíe alkyl) optionally substituted, (Ci-e alkyl)oxyoptionally substituted, (Cvs alkyl )amino-optionally substituted and (Os alkyl)(Ci 4 alkyl)aminooptionally substituted is optionally substituted with 1-4 substituents, each independently selected from -OH, -O-P(O)(OH)2, -O-P(O)( R'R)2, -ORc, -NH2, -NRcRc, -NRcRd, -CO2H, -CO2Rc, -OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc-CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, -NRdSO2Rc, optionally substituted phenyl, optionally substituted 5-6-membered heterocycloalkyl, and optionally substituted 5-6-membered heteroaryl group, wherein said optionally substituted phenyl, 5-6 membered, or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R) 2, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, C1-4 alkyl, halo(Ci-4 alkyl), hydroxy-(Ci-4 alkyl)- , -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-O-P(O)(R'R)2, halo(Ci-4 alkoxy)-, C1- 4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-O-P(O)(OH)2, -(C2-4alkoxy¡)-0-P(0)(R'R) 2, C1-4 alkoxy-(Ci-4 alkoxy)-, -CORd, -CON(Rd)(Rf), and -CO2Rd, R14 is absent, or is H, halogen, or optionally substituted C1-4 alkyl, where said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; R16 is absent, or is H, halogen, or C1-4 alkyl; R15 and R17, each independently, are absent, or are H, cyclopropyl, halogen or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORG, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; o R15y Taken together with the atom or atoms through which they are connected, they form a 5-6 membered ring; o R1sy Taken together with the atom or atoms through which they are connected, they form a 5-6 membered ring; R18 and R19, each independently, are absent, or are H, halogen, optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORG, -NRcRd, -CO2RC , -CONRGRd, -SO2NRcRd, and -OCONRGRd; or R17 and R18 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; Raes H, -RG, -CORG, -CO2H, -CO2RG, -SORG, -SO2RG-CONH2, -CONRGRd, -SO2NH2, -CH2-CO2RG, or -SO2NRcRd; each Rbes independently C1-4 alkyl, halo(Ci-4 alkyl), -(C1-4 alkyl)-OH, -(C1-4 alkyl)-OP(O)(OH)2, -(C1-4 alkyl) -O-P(O)(R'R)2, -(C1-4 alkyl)-O-(Ci-4 alkyl), -(C1-4 alkyl)-N(Re)(Rf), -(C1-4 alkyl)-OCO(Ci-4 alkyl), or -(C1-4 alkyl)-CO-O-(Ci-4 alkyl); LCQfrzn / zznz / q / viAi each Rces independently H, C1-4 alkyl, halo(Ci-4 alkyl), -(C1-4 alkyl)-OH, -(C1-4 alkyl)-OP(O)(OH) 2, -(C1-4 alkyl)-O-P(O)(R'R)2, -(C1-4 alkyl)-O-(Ci-4 alkyl), -(C1-4 alkyl)-N(Re) (Rf), -(C1-4 alkyl)-OCO(Ci-4 alkyl), -(C1-4 alkyl)-CO-O-(Ci-4 alkyl), C3-6 optionally substituted cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, optionally substituted 9-10 membered heteroaryl, -C1-4 alkyl-C36 optionally substituted cycloalkyl, -C1-4 optionally substituted alkyl-phenyl, -C14 optionally substituted 4-6 membered alkylheterocycloalkyl, optionally substituted -C14 5-6 membered alkylheteroaryl, or optionally substituted -C1-4 9-10 membered alkylheteroaryl, wherein the moiety C3-6 cycloalkyl, phenyl, heterocycloalkyl 4-6 membered, 5-6 membered heteroaryl or 9-10 membered heteroaryl of said C3-6 optionally substituted cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, optionally substituted 9-10 membered heteroaryl, -C1-4 alkyl-C36 optionally substituted cycloalkyl, -C1-4 optionally substituted alkylphenyl, -C1-4 optionally substituted 4-6 membered alkylheterocycloalkyl, -C1-4 alkyl -optionally substituted 5-6 membered heteroaryl, or -optionally substituted 9-10 membered -C1-4alkylheteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH) )2, -O-P(O)(R'R)2, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino, C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-OP(O)(OH)2, -(C2-4alkoxy )-0-P(0)(R'R)2, C1-4 alkoxy-(Ci-4 alkoxy)-, -CORd, -CON(Rd)(Rf), and-CO2Rd; each Rdes independently H, hydroxyl, or C1-4 alkyl; each R® is independently H, (C1-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), -CO2(Ci-4 alkyl), -(C1-4 alkyl)amino, -(C1-4 alkyl)-Ci-4 alkoxy, -CO-(5-6 membered heterocycloalkyl optionally substituted), -CO-(Ci-4 alkyl)-(5-6 membered heterocycloalkyl optionally substituted), -CO -(optionally substituted 5-6-membered heteroaryl), -CO-(Ci-4 alkyl)-(optionally substituted 5-6-membered heteroaryl), wherein optionally substituted 5-6-membered heterocycloalkyl or 5-6-membered heteroaryl optionally substituted members are optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-PÍOJÍR'R1^, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy )-, -(C2-4 alkoxy) O-P(O)(OH)2, -(C2-4 alkoxy¡)-0-P(0)(R'R)2, C1-4 alkoxy-(Ci-4 alkoxy)-, CORd, -CON^XRf), and -CO2Rd; each Rfes independently H, hydroxyl, or (C1-4 alkyl); R9 and Rhson, each independently, H or (C1-4 alkyl) or Rs and Rh, taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; and each R1 and R are independently (C1-6 alkyl)oxy-; provided that at least one of (i), (i), or (iii) applies: (i) when s is 0, r is 1, (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are LCQfrzn / zznz / q / viAi each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S 0X9 is N; or (i) when s is 0, r is 1, (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and , -SOzNRcRd, and -OCONRcRden where Rces H; or (ii) when s is 0, r is 1, (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) Wz and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Xe, and -e alkyl)oxy- substituted, (C1-6 alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the (C1-6 alkyl) of said (C1 -6 alkyl) optionally substituted, (C1-6 alkyl)oxy- substituted, (C1-6 alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted is optionally substituted with 1 -4 substituents each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, -N^XR1), -CO2(Rj, -CONCR^ÍRf), phenyl optionally substituted, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O )(OH)2, -O-P(O)(R'R)2, amino, (Ci-e alkyl)amino-, (Ci-s alkyl)(Ci-6 alkyl)amino-, -(C1-6 alkyl )-NHz, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C14 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-O-P(O)( RlRll)2, halo(Ci-4alkoxy)-, C1-4alkoxy-, hydroxy-(C2-4alkoxy)-, -(C24alkoxy)-O-P(O)(OH)2, -(C2-4alkoxy¡ )-O-P(O)(R'R)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy). In some embodiments, the compound is of Formula (lAj, where the compound is of Formula (IA): i CQbzn / zznz / zi / YiAi R14 (IA), or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof. In some embodiments, the compound is of Formula (Vj: R14 CQbzn / zznz / zi / YiAi (Vj or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Υι, Y2, Z1 and Z2 are each independently O, S, C or N; Χι, X2, W1 and W2 are each independently C or N; X3 and X4 are each independently S or NRf; X5es N or CRA2; X6es N or CRA1; Xg is N or CH; R3 and R5 are, each independently, -CON(Rd)(Rj, -CH2N(Rd)(R*), -N(Rd)(R<), -N(Rd)CO(Rf), -CH2N(Rd) CO(R1) or one of R3and R5es -CON(Rd)(Rf), -CH2N(Rd)(Rf), -N(Rd)(Rf), -N^COCR1), or -CH2N(Rd)CO( Rf), and the other of R3 and R5 is H, COOH or -CO2RC; Rces C1-4 alkyl; RA2 and RA1 are, each independently, H, halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, (C1-6 alkyl) optionally substituted, or (Ci-6alkyl)oxy- optionally substituted, wherein the Ci- e alkyl of said (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxyoptionally substituted is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxy, -N( Re)(Rf), CO2(Rf), -CON(Re)(Rf), and -COOH; each R is independently H, hydroxy, or C1-4 alkyl; Rese selected from H, (C1-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), and -CO2(Ci-4 alkyl); each Rfes independently H, hydroxyl, or (C1-4alkyl); R14 and RC2 are each independently absent, or are C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd; R16 and RC1, each independently, are absent, or are H or C1-4 alkyl; and R15, R17, R18, or R19 are each independently absent, or are H, C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2Rc, -CONRcRd, -SO2NRcRd, and -OCONRcRd; provided that at least one of (i), (ii), or (iii) applies: (i) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S or X9 is N; or (¡i) when (a) Ζι, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and SO2NRcRd, and -OCONRcRden where Rces H; or (iii) when (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Xe, and )ox¡- substituted, (C1-6 alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the Ci-e alkyl of said (C1-6 alkyl) optionally substituted, or (Ci-β aIkyl)ox¡- substituted is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxy, -N^XRO, -CO^RO, - CON(Re)(Rf), and -COOH. In some embodiments, the compound is of Formula (V'), wherein the compound is of Formula (V): LCQfrzn / zznz / q / viAi R14 (V), or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one skilled in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein may be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In the event of a conflict, this specification, including its definitions, will prevail. Likewise, the materials, methods and examples are illustrative only and are not intended to be limiting. Other features and advantages of the invention will be apparent from the following detailed description and claims. Detailed description of the invention It is to be understood that references herein to the compounds of any one or more of the Formulas (lj, (lAj, (llj, (lllj, (IVj, or (Vj, and salts thereof)) cover the compounds of the Formula (Ij, (lAj, (llj, (lllj, (IVj, or (Vj, as free bases, or as salts thereof, for example as pharmaceutically acceptable salts thereof. Therefore, in some embodiments, the The invention is directed to compounds of any one or more of the Formulas (Ij, (lAj, (IIj, (lllj, (IVj, or (Vj, as the free base. In some embodiments, the invention is directed to the compounds of any one or more of Formulas (I j, (IA j, (II j, (lllj, (IVj, or (Vj, and salts thereof. In some embodiments, the invention is directed to compounds of any one or more of the Formulas (I j, (lAj, (II j, (lllj, (IVj, or (Vj, and pharmaceutically acceptable salts thereof. Compounds of any one or more of Formulas (I j, (lAj, (II j, (lllj, (IVj, or (Vj), or salts thereof, including pharmaceutically acceptable salts thereof, are STING modulators Accordingly, this invention provides a compound of any one or more of the Formulas (lj, (lAj, (IIj, (lllj, (IVj, or (Vj), or a salt thereof, including a pharmaceutically acceptable salt of the themselves, for use in therapy. The invention provides the use of a compound of any one or more of the Formulas (lj, (lAj, (llj, (lllj, (IVj, or (Vj, or a pharmaceutically acceptable salt thereof , as an active therapeutic substance in the treatment of a STING-mediated disease or disorder. In some embodiments, a compound of any one or more of the Formulas (lj, (lAj, (llj, (lllj, (IVj, or (Vj, or a salt thereof, including a pharmaceutically acceptable salt thereof, for use in the treatment of a disease mediated by STING agonism or antagonism. The invention also provides a compound of any one or more of Formulas (I j, (lAj, (llj, (lllj, (IVj, or (V), or a salt thereof, including a pharmaceutically acceptable salt thereof , for use in the manufacture of a medicament for the treatment of a STING-mediated disease or disorder. The invention is also directed to a method for modulating STING, wherein the method comprises contacting a cell with a compound of any one or more of Formulas (lj, (lAj, (llj, (lllj, (IVj, or ( Vj, or a salt thereof, including a pharmaceutically acceptable salt thereof. The invention is also directed to a method of treating a STING-mediated disease or disorder comprising administering a therapeutically effective amount of a compound according to one or plus any of the Formulas (lj, (lAj, (llj, (lllj, (IVj, or (Vj, or a salt of the LCQfrzn / zznz / q / viAi themselves, including a pharmaceutically acceptable salt thereof, to a patient (a human or other mammal) in need. Such STING-mediated diseases or disorders include inflammation, allergic and autoimmune diseases, infectious diseases, cancer, and precancerous syndromes. Likewise, STING modulators may be useful as immunogenic composition or vaccine adjuvants. The present invention is also directed to a pharmaceutical composition comprising a compound according to any one or more of the Formulas (Ij, (lAj, (llj, (III j, (IVj, or (Vj, or a salt thereof , including a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient The invention is directed to a pharmaceutical composition for the treatment of a STING-mediated disease or disorder, wherein the composition comprises a compound according to any one or more of the Formulas (Ij, (lAj, (llj, (IIIj, (IVj, or (Vj), or a salt thereof, including a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. Definitions The chemical names provided for the intermediate compounds and / or the compounds of this invention described herein may refer to any one of the tautomeric representations of such compounds (in some cases, such alternative names are provided in the experimentation section). It should be understood that any reference to a named compound (an Intermediate compound or a compound of the invention) or a structurally represented compound (an intermediate compound or a compound of the invention) is intended to encompass all tautomeric forms, including zwitterionic forms of said compounds and any mixture thereof. (1 ) It is understood that, in any one or more of the Formulas (Ij, (lAj, (llj, (IIIj, (IVj, or (Vj, when present, denotes Ring 1 which may be specified according to the various forms ( ?) of embodiment described herein; and, when present, denotes Ring 2 which may be specified in accordance with the various embodiments described herein. It is to be understood that the embodiments for a compound of Formula (I j, (lAj, (llj, (III j, (IVj, or (Vj,)) are intended to encompass the Formulas (I j, (lAj, (llj, (III j, (IVj, and (Vj when applicable. It is to be understood that the terms in some embodiments, in some embodiments of the present invention, and in some embodiments of a compound of the present invention may be used interchangeably, where appropriate. The term alkyl, as used herein, represents a saturated, linear or branched hydrocarbon group having the specified number of carbon atoms. The term C1-4 alkyl refers to a linear or branched alkyl moiety comprising 1 to 4 carbon atoms. Exemplary alkyls include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, / -butyl, pentyl and hexyl. LCQfrzn / zznz / q / YiAi When a substituent term such as alkyl is used in combination with another substituent term, for example, as in hydroxy(Ci-4 alkyl), the linking substituent term (for example, alkyl) is intended to encompass a divalent moiety. , where the point of attachment is through that linking substituent. Examples of hydroxy(Ci-4 alkyl) groups include, but are not limited to, hydroxymethyl, hydroxyethyl, and hydroxyisopropyl. The term halo(alkyl), as used herein, represents a saturated, linear or branched hydrocarbon group having the specified number (n) of carbon atoms and one or more (up to 2n+l) halogen atoms. For example, the term halo(Ci-4 alkyl) represents a group having one or more halogen atoms, which may be the same or different, on one or more carbon atoms of an alkyl moiety comprising 1 to 4 atoms. carbon. Examples of halo(Ci-4 alkyl) groups include, but are not limited to, -CF3 (trifluoromethyl), -CCb (trichloromethyl), 1,1-difluoroethyl, 2,2,2-trifluoroethyl, and hexafluoroisopropjium. The term alkenyl, as used herein, refers to a linear or branched hydrocarbon group having the specified number of carbon atoms and at least 1 and up to 3 carbon-carbon double bonds. Examples include ethenyl and propenyl. The term alkynyl, as used herein, refers to a linear or branched hydrocarbon group having the specified number of carbon atoms and at least 1 and up to 3 carbon-carbon triple bonds. Examples include ethinyl and propynyl. The term alkoxy- or (alkyl)oxy-, as used herein, refers to an alkyl-oxy group comprising an alkyl moiety, having the specified number of carbon atoms, linked through a linking atom. of oxygen. For example, the term C1-4 alkoxy represents a saturated, linear or branched hydrocarbon moiety having at least 1 and up to 4 carbon atoms linked through an oxygen bonding atom. Exemplary C1-4 alkoxy- or (C1-4 alkyl)oxy- groups include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, s-butoxy, and f-butoxy. The term halo(alkoxy)-, as used herein, represents a saturated, linear or branched hydrocarbon group having the specified number (n) of carbon atoms and one or more (up to 2n+l) halogen atoms, linked through an oxygen bonding atom. For example, the term halo(Ci4 alkoxy)- refers to a haloalkyl-oxy- group, which comprises a halo(Ci-4 alkyl) moiety attached through an oxygen linking atom. Exemplary halo(Ci-4 alkoxy)- groups include, but are not limited to, -OCHF2 (difluoromethoxy), -OCF3 (triflu gold methoxy), -OCH2CF3 (trifluoroethoxy), and -OCH(CF3)2 (hexafluoroisopropoxy). The term amino, as used herein, refers to a substituent comprising at least one nitrogen atom. Specifically, the substituents -NH2, -NH(Ci-4 alkyl), alkylamino, or (C1-4 alkyl)amino- or (C1-4 alkyl)(Ci-4 alkyl)amino- or dialkylamino, amide-, carbamide- , urea, and sulfonamide are included in the term “amino.” The term carbocyclic group or moiety, as used herein, refers to a cyclic group or moiety in which the ring members are carbon atoms, which may be saturated, partially unsaturated (non-aromatic), or completely unsaturated (aromatic). ). LCQfrzn / zznz / q / viAi The term cycloalkyl, as used herein, refers to a non-aromatic, saturated hydrocarbon ring group comprising the specified number of ring carbon atoms. For example, the term C3-6 cycloalkyl refers to a cyclic group having three to six ring carbon atoms. Examples of C3-6 cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term "heterocyclic group or moiety," as used herein, refers to a cyclic group or moiety having, as ring members, atoms of at least two different elements, wherein the cyclic group or moiety may be partially saturated. unsaturated (non-aromatic) or completely unsaturated (aromatic). The term heteroatom, as used herein, refers to a nitrogen, sulfur or oxygen atom; for example, a nitrogen atom or an oxygen atom. The term heterocycloalkyl, as used herein, refers to a non-aromatic, monocyclic or bicyclic group comprising 3-10 ring atoms and comprising one or more (generally one or two) independently selected heteroatom ring members. between oxygen, sulfur and nitrogen. The point of attachment of a heterocycloalkyl group may be any suitable carbon or nitrogen atom. Examples of heterocycloalkyl groups include, but are not limited to, aziridinyl, thiiranyl, oxiranyl, azetidinyl, oxetanyl, thietanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, 1,3-dioxolanyl, piperidinyl, piperazinyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, 1,3- dioxanyl, 1,4-dioxanyl, 1,3-oxathiolanyl, 1,3-oxathianyl, 1,3-dithianyl, 1,4-oxathiolanyl, 1,4-oxathianyl, 1,4-dithianyl, morpholinyl, thiomorpholinyl, and hexahydro -11,4-diazepinyl. Examples of 4-membered heterocycloalkyl groups include oxetanyl, thietanyl and azetidinyl. The term 5-6 membered heterocycloalkyl, as used herein, refers to a saturated monocyclic group, comprising 5 or 6 ring atoms, including one or two heteroatoms independently selected from oxygen, sulfur and nitrogen. Illustrative examples of 5-6 heterocycloalkyl groups include, but are not limited to, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, piperazinyl, morpholinyl, and thiomorpholinyl. The term "heteroaryl", as used herein, refers to a monocyclic or bicyclic aromatic group comprising 5 to 10 ring atoms, including 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein at least a part of the group is aromatic. For example, this term encompasses bicyclic heterocyclic-aryl groups comprising either a phenyl ring fused to a heterocyclic moiety or a heteroaryl ring moiety fused to a carbocyclic moiety. The point of attachment of a heteroaryl group can be any suitable carbon or nitrogen atom. The term 5-6 membered heteroaryl, as used herein, refers to a monocyclic aromatic group comprising 5 or 6 ring atoms, including at least one carbon atom and 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur. Selected 5-membered heteroaryl groups contain a nitrogen, oxygen or sulfur heteroatom in the LCQfrzn / zznz / q / YiAi ring, and optionally contain 1, 2 or 3 additional nitrogen atoms in the ring. Selected 6-membered heteroaryl groups contain 1,2, or 3 nitrogen heteroatoms in the ring. Examples of 5-membered heteroaryl groups include furyl (furanyl), thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, and oxadiazolyl. Selected 6-membered heteroaryl groups include pyridinyl (pyridyl), pyrazinyl, pyrimidinyl, pyridazinyl and triazinyl. The term 9-10 membered heteroaryl, as used herein, refers to a bicyclic aromatic group comprising 9 or 10 ring atoms, including 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur. Examples of 9-membered heteroaryl groups (6,5-fused heteroaryl) include benzothienyl, benzofuranyl, indolyl, indolinyl (dihydroindolyl), isoindolyl, isoindolinyl, indazolyl, isobenzofuryl, 2,3-dihydrobenzofuryl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoisothiazolyl , benzimidazolyl, benzoxadiazolyl, benzothiadiazolyl, benzotriazolyl, purinyl, imidazopyridinyl, pyrazolopyridinyl, triazolopyridinyl and 1,3-benzodioxolyl. Examples of 10-membered heteroaryl groups (6,6-fused heteroaryl) include, but are not limited to, quinolinyl (quinolyl), isoquinolyl, phthalazinyl, naphthyridinyl (1,5-naphthyridinyl, 1,6-naphthyridinyl, 1,7-naphthyridinyl, 1,8-naphthyridinyl), quinazolinyl, quinoxalinyl, 4H-quinolizínyl, 1,2,3,4-tetrahydroquinolinyl (tetrahydroquinolinyl), 1,2,3,4-tetrahydroisoquinolinyl (tetrahydroisoquinolinyl), cinnolinyl, pteridinyl, and 2,3dihydrobenzo[b][l,4]dioxin. The terms halogen and halo, as used herein, refer to a halogen radical; for example, a fluorine, chlorine, bromine or iodine substituent. The term oxo, as used herein, refers to a double-bonded oxygen moiety; for example, if it bonds directly to a carbon atom, it forms a carbonyl moiety (C = 0). The term hydroxy or hydroxyl, as used herein, is intended to refer to the -OH radical. The term cyano, as used herein, refers to a nitrile group, -ΟξΝ. The term optionally substituted, as used herein, indicates that a group (such as an alkyl, cycloalkyl, alkoxy, heterocycloalkyl, aryl or heteroaryl group) or ring or moiety may be unsubstituted, or the group, ring or moiety may be substituted with one or more substituents as defined in the definitions of substituents (A, R3, etc.) given herein. In the case where the groups can be selected from a number of alternative groups, the selected groups may be the same or different. The term independently, as used herein, means that when more than one substituent is selected from a number of possible substituents, those substituents may be the same or different. The term pharmaceutically acceptable, as used herein, refers to those compounds, materials, compositions and dosage forms that are, within the scope of good medical judgment, suitable for use in contact with the tissues of humans and animals without LCQfrzn / zznz / q / viAi excessive toxicity, irritation, or other problem or complication, proportional to a reasonable risk / benefit ratio. The length of the linking groups defined here represents the lowest number of atoms in a direct chain composed of -RB1-B-RB2- and / or -RC1-D-RC2-. For example, when B is an optionally substituted phenyl, the linking group -RB1-B-RB2- may be represented as -(CH2)-phenyl(CH2)-. This linking group is characterized as a 4-membered linking group when the 2 -(CH2)- residues are located on adjacent carbon atoms of the phenyl ring (1,2-substituted phenyl). In some embodiments, this linking group is characterized as a 6-membered linking group when the 2-(CH2)- residues are substituted at para positions on the phenyl ring (1,4-substituted phenyl). Any alkyl, alkenyl or alkynyl group or residue of B or D will be understood to be a linear or branched alkyl, alkenyl or alkynyl group or residue. For example, a linking group -RB1-B-RB2-, where B is -Cmo alkyl- can contain an 8 membered linking group having one branched group (C1-4 alkyl) or 2-4 branched groups ( C1-3 alkyl); for example, 4 branched methyl groups (2 gem-dimethyl groups) or 2 branched methyl groups. The terms compound(s) of the invention or compound(s) of this invention, as used herein, mean a compound of Formula (I'), Formula (IA'), Formula (II'), Formula (III '), Formula (IV'), and Formula (V') as defined herein, in any form, that is, any tautomeric form, any isomeric form, any saline or non-saline form (for example, as a form base or free acid, or as a salt, particularly a pharmaceutically acceptable salt thereof) and any physical form thereof (for example, including non-solid forms (for example, liquid or semi-solid forms), and solid forms ( for example, amorphous or crystalline forms, specific polymorphic forms, solvate forms, including hydrate forms (e.g., mono-, di-, and hemi-hydrates), and mixtures of various forms. Accordingly, compounds of one or more of any of Formulas (I'), (ΙΑ'), (ΙΓ), (III'), (IV'), or (V') are included within the present invention. , as defined herein, in any salt or non-salt form and any physical form thereof, and mixtures of various forms. Although these are included within the present invention, it will be understood that the compounds of one or more of any of the Formulas (I'), (ΙΑ'), (ΙΓ), (III'), (IV'), or (V'), as defined herein, in any salt or non-salt form, and any physical form thereof, may have varying levels of activity, different bioavailabilities and different handling properties for formulation purposes. Compound of the present invention In some aspects, the present invention provides a compound of Formula (IA') LCQfrzn / zznz / q / viAi R14 LCQfrzn / zznz / q / viAi or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: W1X1, Yi, Zi, W2, X2, Y2, and Z2 are, each independently, O, S, C , or N; X3 and X4 are, each independently, S or NRf; X5es N or CRA2; Xs is N or CRA1; Xa is N or CR4; r and s are, each independently, 0 or 1; p is 1 or 2; the total of r and s is 1 or 2; RA1 and ra2 are cac|a un0 independently, H, halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, O-P(O)(OH)2, -O-P(OXR'R)2, -N(Re)( Rf), -CO2Rf, -N(Rf)CORb, -N(R9)SO2(Ci-4 alkyl)-N(Re)(Rf), N(R9)CO(Ci-4 alkyl)-N( Rh)(Rf), (Ove alkyl) optionally substituted, (C1-6 alkyl)oxy- optionally substituted, (C1-6 alkyl)amino- optionally substituted, and (C1-5 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the (C1-6 alkyl) of said (C1-6 alkyl) optionally substituted, (Ci-β alkyl)oxyoptionally substituted, (C1-6 alkyl)amino-optionally substituted and (Ci-e alkyl)( Optionally substituted Ci-4 alkyl)amino is optionally substituted with 1-4 substituents, each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(RIR)2, C1-4 alkoxy-, - ΙψΡθχΡ1), CC^Rf), -CONCReXRj, optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -Ο-Ρ(Ο)(Ρ'Ρ)2, amino, (Ci-6alkyl)amino-, (C1-6 alkyl)(Ci- 6 alkyl)amino, -(C1-6 alkyl)-NH2, halo(Ci-s alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-OP(O)(R'R)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4alkoxy) -0-P(0)(OH)2, -(C2-4 alkoxy)-OPIOXR'R'X, -C1-4 alkyl-(Ci 4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy) -; when r is 0, RB1 and RB2 are, each independently, H, Ci-e optionally substituted alkyl, halo(Ci-e alkyl), C2-6 optionally substituted alkenyl, C2-6 optionally substituted alkynyl, C3-6 optionally substituted cycloalkyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 910 membered heteroaryl, wherein said Ci-β optionally substituted alkyl, Cz-e optionally substituted alkenyl, Cz-e optionally substituted alkynyl, C36 optionally substituted cycloalkyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, nitro, -Rc, OH, -O-P(O)(OH)2, -Ο-Ρ(Ο)(Ρ'Ρ)2 -ORg, -NH2, -NRcRc, -NRGRd, -OCORC, -CO2H, -CO2RC, -SORC, -SO2RC, -CONH2, -CONRGRd, -SO2NH2, -SO2NRGRd, -OCONH2, -OCONRGRd, -NRdCORG, -NRdSORG, -NRdCO2RG, and -NRdSOzRG; when s is 0, RC1 is absent, or is H, halogen, or C1-4 alkyl and RC2 is absent or is optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl group is optionally substituted with a substituent selected from - ORG, -NRGRd, -CO2RG, -CONRGRd, SO2NRGRd, and -OCONRcRd; when r is 1, RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and RB2, forms a linking group, where B is a bond or B is -halo(Ci w alkyl)-, - C1-10 alkyl optionally substituted, -C2-10 alkenyl- optionally substituted, -C2-10 alkynyl- optionally substituted, -C1-6 alkyl-O-Ci-6 alkyl- optionally substituted, -C1-6 alkyl-NRa-Ci- 6-alkyl- optionally substituted, C3-6 optionally substituted cycloalkyl, optionally substituted phenyl, optionally substituted 4-6-membered heterocycloalkyl, optionally substituted 5-6-membered heteroaryl, -C1-4 alkyl(C3-6 cycloalkyl)-Ci -4 alkyl- optionally substituted, -C1-4 alkyl-phenyl-Ci-4 alkyl- optionally substituted, -C1-4 alkyl-(4-6 membered heterocycloalkyl)-Ci-4 alkyl- optionally substituted, or -C1- 4 alkyl-(5-6 membered heteroaryl)-Ci 4 alkyl- optionally substituted, wherein the alkyl moiety of said -C1-10 alkyl- optionally substituted, -C2-10 alkenyloptionally substituted, -C2-10 alkynyl- optionally substituted , -C1-6 alkyl-O-Ci-6 alkyl optionally substituted, -C1-6 alkyl-NRa-Ci-6 alkyl- optionally substituted, -C1-4 alkyl-(C3-6 cycloalkyl)-Ci-4 alkyl- optionally substituted, -C1-4 alkyl-phenyl-Ci-4 alkyl- optionally substituted, C1-4 alkyl-(4-6 membered heterocycloalkyl)-Ci-4 alkyl- optionally substituted, or -C1-4 alkyl(5-membered heteroaryl) -6 membered-Ci-4 alkyl)- optionally substituted is optionally substituted with 1 or 2 substituents, each independently selected from halogen, halo(Ci-4 alkyl), -OH, -OP(O)(OH)2, - O-P(O)(R'R)2, -ORg, -NH2, -NRcRd, -OCORG, -CO2H, -CO2RG, -SORG, -SO2RG, -CONH2, CONRGRd, -SO2NH2, -SO2NRcRd, -OCONH2, - OCONRGRd, -NRdCORc, -NRdSORc, -NRdCO2RG, and NRdSO2RG, and the C3-6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said optionally substituted C3-6cycloalkyl, optionally substituted phenyl, 4-heterocycloalkyl LCQfrzn / zznz / q / viAi optionally substituted membered, optionally substituted 5-6 membered heteroaryl, -C1-4 alkyl(C3-6 cycloalkyl)-Ci-4 alkyl- optionally substituted, -C1-4 alkyl-phenyl-Ci- 4-alkyl- optionally substituted, -C1-4 alkyl-(4-6-membered heterocycloalkyl)-Cy-4-alkyl- optionally substituted, or -C1-4 alkyl-(5-6-membered heteroaryl) -Ci-4 alkyl- optionally substituted is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -OP(O)(OH)z, -O-P(O)(OR'R)2, amino, (Ci-4alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, C14 alkyl, halo(Ci4 alkyl), halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-( C2 4 alkoxy)-, -(C2 4 alkoxy)-0-P(0)(OH)2, -(C2 4 alkoxy)-OΡ(Ο)(Ρ'Ρ)2, and C1-4 alkoxy-(Ci -4 alkoxy)-; when s is 1, W1 and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D taken together with RC1 and RC2 forms a linking group, where D is halo(Ci -i2alkyl)-, -C1-12alkyl- optionally substituted, -C2-i2alkenyl- optionally substituted, -C2-12alkynyl- optionally substituted, -Ci-β alkyl-O-Ci-6alkyl- optionally substituted, -C1- 6 alkyl-NRa-Ci6 optionally substituted alkyl-, -C1-6 alkyl-(C3-6cycloalkyl)-Ci-6 optionally substituted alkyl-, -C1-6 alkyl-phenyl-Optionally substituted Ci-6 alkyl-, -C1- 6-alkyl-(4-6 membered heterocycloalkyl)-Ci-6 optionally substituted alkyl-, or -C1-6 alkyl-(5-6 membered heteroaryl)-Ci-6 optionally substituted alkyl-, wherein the alkyl moiety of said -C1-12 optionally substituted alkyl-, -C1-6 optionally substituted alkenyl, -C2-12 optionally substituted alkynyl-, -Ci-e alkyl-O-Ci-6 optionally substituted alkyl, -Ci-e alkyl-NRa-Ci- 6-alkyl- optionally substituted, -C1-6 alkyl-(C3-6 cycloalkyl)-Ci-6 alkyl- optionally substituted, -C1-6 alkyl-phenyl-Ci-6 alkyl- optionally substituted, C1-6 alkyl- (4-6 membered heterocycloalkyl)-Ci-6 alkyl- optionally substituted, or -C1-6 alkyl(5-6 membered heteroaryl)Ci-6 alkyl- optionally substituted is optionally substituted with 1 or 2 substituents , each independently selected from halogen, halo(Ci-4alkyl), -OH, -OP(O)(OH)2, -O-P(O)(R'R)2, -ORc, -NH2, -NRcRd, -OCORC, -CO2H, -CO2RC, -SORC, -SO2RC, -CONH2, CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and NRdSO2Rc, and remainder Csecycloalkyl, phenyl , 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl of said -C1-6 alkyl-(C3-6 cycloalkyl)-Ci-6 alkyl- optionally substituted, -C1-6 alkyl-phenyl-Ci-6 alkyloptionally substituted, -C1-6 alkyl-(4-6 membered heterocycloalkyl)-Ci-6 alkyl- optionally substituted, or -Ci-e alkyl-(5-6 membered heteroaryl)-Ci-6 alkyl- optionally substituted is optionally substituted substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, O-P(O)(R'R)2, amino, (C1-4 alkyl)amino-, (C1 -4 alkyl)(Ci-4 alkyl)amino, C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4alkoxy)-OP(O)(OH)2, -(C2-4alkoxy)-O-P(O)(R1R)2, and C1-4alkoxy-(Ci-4alkoxy)-; R3 and R5 are each independently -CON(Rd)(Rj, -CH2N(Rd)(Rf), -N(Rd)(R*), -N(Rd)CO(Rf), -ΟΗ2Ν(Ρό)ΟΟ (Ρί), or one of R3 and R5 is -CON(Rd)(Rf), -CH2N(Rd)(Rf), -N(Rd)(Rj, -NfR^COÍR1), or -CH2N(Rd)CO(R '), and the other of R3 and R5 is H, COOH, or -CO2RC; LCQfrzn / zznz / q / viAi R4 and R6 are selected, each independently, from H, halogen, halo(Ci-6 alkyl), halo(Ci-6 alkoxy)-, hydroxyl, -O-P(O)(OH)2, O-PIOXR'R^, - NH2, -NRCRC, -NRcRd, -CORC, -CO2RC, N(Rd)CORc, -N(Rd)SO2Rc, -N(R9)SO2(Ci-2alkylj-NÍR^CR1), -N(R9)CO( Ci-2 alkyl)-N(Rh)(Rf), (Ci-6 alkyl) optionally substituted, (C1-6 alkyl)ox¡- optionally substituted, (C1-6 alkyl)amino- optionally substituted, and (C1- 6 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the (Ci-e alkyl) of said (Cí e alkyl) optionally substituted, (Ci-e alkyl)oxyoptionally substituted, (Cvs alkyl)amino- optionally substituted and (Cve alkyl)(Ci 4 alkyl)aminooptionally substituted is optionally substituted with 1-4 substituents, each independently selected from -OH, -O-P(O)(OH)2, -O-P(O)(R'R )2, -ORC, -NH2, -NRCRC, -NRcRd, -CO2H, -CO2Rc, -OCORc, -CO2H, -CO2Rg, -SORc, -SO2Rc-CONH2, -CONRcRd, -SO2NH2, -SO2NRGRd, OCONH2, - OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, -NRdSO2Rc, optionally substituted phenyl, optionally substituted 5-6-membered heterocycloalkyl, and optionally substituted 5-6-membered heteroaryl group, wherein said optionally substituted phenyl, 5-6-membered heterocycloalkyl membered, or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino , (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, C1-4 alkyl, halo(Ci-4 alkyl), hydroxy-(Ci-4 alkyl)-, -( C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-O-P(O)(RlR)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-( C2-4 alkoxy)-, -(C2-4 alkoxy)-O-P(O)(OH)2, -(02-4 3ΐοοχί)-0-Ρ(0)(Ρ'Ρ)2, Ci-4alkoxy-( Ci-4 alkoxy)-, -CORd, -CON(Rd)(Rf), and -CO2Rd, R14 is absent, or is H, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; R16 is absent, or is H, halogen, or C1-4 alkyl; R15 and R17, each independently, are absent, or are H, cyclopropyl, halogen or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORG, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; o R15y Taken together with the atom or atoms through which they are connected, they form a 5-6 membered ring; o R1sy Taken together with the atom or atoms through which they are connected, they form a 5-6 membered ring; R18 and R19, each independently, are absent, or are H, halogen, optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORG, -NRcRd, -CO2RC , -CONRGRd, -SO2NRcRd, and -OCONRGRd; or R17 and R18 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; Raes H, -RG, -CORG, -CO2H, -CO2RG, -SORG, -SO2RG-CONH2, -CONRGRd, -SO2NH2, -CH2-CO2RG, or -SO2NRGRd; each Rbes independently C1-4 alkyl, halo(Ci-4 alkyl), -(C1-4 alkyl)-OH, -(C1-4 alkyl)-OP(O)(OH)2, -(C1-4 alkyl) -O-P(O)(R'R)2, -(C1-4 alkyl)-O-(Ci-4 alkyl), -(C1-4 alkyl)-N(Re)(Rf), -(C1-4 alkyl)-OCO(Ci-4 alkyl), or -(C1-4 alkyl)-CO-O-(Ci-4 alkyl); CQbzn / zznz / zi / YiAi each Rces independently H, C1-4 alkyl, halo(Ci-4 alkyl), -(C1-4 alkyl)-OH, -(C1-4 alkyl)-OP(O)(OH) 2, -(C1-4 alkyl)-O-P(O)(R'R)2, -(Ci-4alkyl)-O-(Ci-4 alkyl), -(C1-4 alkyl)-N(R®) (Rf), -(C1-4 alkyl)-OCO(Ci-4 alkyl), -(C1-4 alkyl)-CO-O-(Ci-4 alkyl), C3-6 optionally substituted cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, optionally substituted 9-10 membered heteroaryl, -C1-4 alkyl-C36 optionally substituted cycloalkyl, -C1-4 optionally substituted alkyl-phenyl, -C14 optionally substituted 4-6 membered alkylheterocycloalkyl, optionally substituted -C14 5-6 membered alkylheteroaryl, or optionally substituted -C1-4 9-10 membered alkylheteroaryl, wherein the moiety C3-6 cycloalkyl, phenyl, heterocycloalkyl 4-6 membered, 5-6 membered heteroaryl or 9-10 membered heteroaryl of said C3-6 optionally substituted cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, optionally substituted 9-10 membered heteroaryl, -C1-4 alkyl-C36 optionally substituted cycloalkyl, -C1-4 optionally substituted alkylphenyl, -C1-4 optionally substituted 4-6 membered alkylheterocycloalkyl, -C1-4 alkyl -optionally substituted 5-6 membered heteroaryl, or -optionally substituted 9-10 membered -C1-4alkylheteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH) )2, -O-P(O)(R'R)2, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino, C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-OP(O)(OH)2, -(C2-4 alkoxy )-0-P(0)(R'R)2, C1-4 alkoxy-(Ci-4 alkoxy)-, -CORd, -CON(Rd)(Rf), and -CO2Rd; each Rdes independently H, hydroxyl, or C1-4 alkyl; each R® is independently H, (C1-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), -CO2(Ci-4 alkyl), -(C1-4 alkyl)amino, -(C1-4 alkyl)-Ci-4 alkoxy, -CO-(5-6 membered heterocycloalkyl optionally substituted), -CO-(Ci-4 alkyl)-(5-6 membered heterocycloalkyl optionally substituted), -CO -(optionally substituted 5-6-membered heteroaryl), -CO-(Ci-4 alkyl)-(optionally substituted 5-6-membered heteroaryl), wherein optionally substituted 5-6-membered heterocycloalkyl or 5-6-membered heteroaryl optionally substituted members are optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-PtOXR'R^, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy )-, -(C2-4 alkoxy) O-P(O)(OH)2, -(C2-4 alkoxy¡)-0-P(0)(R'R)2, C1-4 alkoxy-(Ci-4 alkoxy)-, CORd, -CON(Rd)(Rf), and -CO2Rd; each Rfes independently H, hydroxyl, or (C1-4 alkyl); R9 and Rhson, each independently, H or (C1-4 alkyl) or Rs and Rh, taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; and each R1 and R are independently (C1-6 alkyl)oxyl-; provided that at least one of (i), (i), or (i!) applies: (i) when s is 0, r is 1, (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are LCQfrzn / zznz / q / viAi each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S 0X9 is N; or (ii) when s is 0, r is 1, (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) Wi, W2, X1 and , -SOzNRcRd, and -OCONRcRden where Rces H; or (ii) when s is 0, r is 1, (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) Wz and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Xe, and -e alkyl)oxy- substituted, (C1-6 alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the (C1-6 alkyl) of said (C1 -6 alkyl)optionally substituted, (C1-6 alkyl)oxy- substituted, (C1-6 alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted is optionally substituted with 1 -4 substituents each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, -N(Re)(Rj, -CO2(Rj, -CON(Re) (Rj, optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (Ci-e alkyl)amino-, (Ci-s alkyl)(Ci-6 alkyl)amino-, -( C1-6 alkyl)-NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C14 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-O-P (O)(RlRl)2, halo(Ci-4alkoxy)-, C1-4alkoxy-, hydroxy-(C2-4alkoxy)-, -(C24alkoxy)-O-P(O)(OH)2, -(C2 -4alkoxy¡)-O-P(O)(R'R)2, -C1-4alkyl-(Ci-4alkoxy), and C1-4alkoxy-(Ci-4alkoxy)-. In some embodiments, the compound is of Formula (lAj, where the compound is of Formula (IA): LCQfrzn / zznz / q / viAi R14 or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof. In some aspects, the present invention provides a compound of Formula (Ij R14 LCQfrzn / zznz / q / viAi or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Wi.Xi, Yi, Zi, W2, X2, Y2, Z2, r, s, X3, X4X5, Xe, X9, R3, R5, R14, Ra, Rb, Rc, Rd, Re, Rf, R1, and R are, each independently, as defined for Formula (lAj; when r is 0, RB1 and RB2 are each independently as defined for Formula (IA'); when s is 0, RC1 is as defined for Formula (lAj; when r is 1, RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and RB2, forms a linking group, where B is a bond or B is as defined for Formula (1Aj; when s is 1, Wi and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D taken together with RC1 and RC2 forms a link group, where D is as defined for the Formula (lAj; R16 is absent, or is H, halogen, or C1-4 alkyl; R15 and R17, each independently, are absent, or are H, cyclopropyl, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd , -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; or R15and R19 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; R18 and R19 are, each independently, as defined for Formula (1Aj; or R17 and R18 taken together with the atom(s) through which they are connected, form a 5-6 membered ring; Ra and Rh are each independently, as defined for Formula (lAj or Ra and Rh taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; and provided that at least one of (i), (ii), or (iii) of Formula (lAj. In some aspects, the present invention provides a compound of Formula (Ij or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, provided that at least one of (i), (i) or (i¡) is applied ): (i) when s is 0, r is 1, (a) Zi, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Ζι, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or Xs is N; or (i) when s is 0, r is 1, (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and , -SO2NRcRd, and -OCONRcRden where Rces H; or (iii) when s is 0, r is 1, (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Xb, and ¡- substituted, (C1-6 alkyl)amino- optionally substituted, and (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the (C1-6 alkyl) of said (C1-6 alkyl) substituted and (C1-6 alkyl)oxy-substituted is substituted with 1-4 substituents each independently selected from -O-P(O)(OH)2, -O-P(O)(R'R)2, optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH)2 , -OP(O)(R'R)2, amino, (Ove alkyl)amino-, (Ove alkyl)(Ci-e alkyl)amino-, -(Ci-e alkyl)-NH2, halo(Ci-e alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkylj-O-PIOXR'R1^, halo(Ci-4 alkoxy )-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-O-P(O)(OH)2, -(C2-4alkoxy¡)-O-P(O)(R 'R)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-; and the (C1-6 alkyl) of said (C1-6 alkyl)amino- optionally substituted and (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted is optionally substituted with 1-4 substituents each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(RIR)2, -N(Re)(Rf), -CCbCRj, CON^XRf), optionally substituted phenyl, and a 5-heteroaryl group 6-membered optionally substituted, wherein said optionally substituted phenyl or 5-6-membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O) (R'R)2, amino, (Ci-6alkyl)amino-, (C1-6alkyl)(Ci-6alkyl)amino, -(C1-6alkyl)-NH2, halo(Ci-6alkyl), hydroxy -(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-OP(O)(R'R)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4alkoxy)-0-P(0)(OH)2, -(C2-4 alkoxy)-OP(O) (R'R)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments, the compound is of Formula (I'), wherein the compound is of Formula (I): I CQb7n / 77n7 / =l / YIAI (YO), LCQfrzn / zznz / q / YiAi or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof. In some aspects, the present invention provides a compound of Formula (II j or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: W2, X2, Y2, Z2, r, s, X3, X4X5, Xe, the Formula (lAj; when r is 0, RB1 and RB2 are, each independently, as defined in Formula (lAj; when s is 0, RC1 is as defined in Formula (IA'); when r is 1, RB1 and RB2 are, each independently, -CH2-, and B, taken together with RB1 and RB2, forms a bonding group, where B is a bond or B is as defined in Formula (lAj; when s is 1, Z2 is C or N, RC1 and RC2 are, each independently, -CH2-, and D taken together with RC1 and RC2, forms a linking group, where D is as defined in Formula (lAj; R16 is absent, or is H, halogen, or C1-4 alkyl; R17 is absent, or is H, cyclopropyl, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; R18 is absent, or is H, halogen, optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRGRd, -SO2NRcRd, and -OCONRcRd; or R17 and R18 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; R19 is absent, or is H, halogen, optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; and Rg and Rhson, each independently, as defined in Formula (IA') or R9y Rhtaken together with the atom or atoms through which they are connected, form a 5-6 membered ring. In some aspects, the present invention provides a compound of Formula (II j, or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, provided that, when s is 0, r is 1, (a) Z2 and Y2 are each N, W2 and X2 are each C; or (b) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of ) substituted, (C1-6 alkyl)oxy-substituted, (C1-6 alkyl)amino- optionally substituted, and (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein (Ci-β alkyl) of said (Ci-β alkyl) substituted and (C1-6 alkyl)oxy-substituted is optionally substituted with 1-4 substituents each independently selected from -OP(O)(OH)2, -O-PIOXR' R^, optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, - O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (Ci-6alkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino, -(C1-6 alkyl)-NH2, halo(Ci-e alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-OΡ( Ο)(Ρ'Ρ)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2 4 alkoxy)-, -(C2 4alkoxy)-0-P(0)(OH)2, -(C2 4 alkoxy)-OΡίΟχΡ'Ρ1^, -Ci-4 alkyl-(Ci 4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-; and the (C1-6 alkyl) of said (C1-6 alkyl)amino- optionally substituted and (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted is optionally substituted with 1-4 substituents each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, -N(Re)(R*), -CO2(Rf), CON^XRO, optionally substituted phenyl, and a optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (Ci-6alkyl)amino-, (C16 alkyl)(Ci-6 alkyl)amino, -(C1-6 alkyl)-NH2, halo(Ci-6 alkyl ), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-OΡίΟχΡ^'Χ, halo(Ci-4 alkoxy)- , C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4alkoxy)-0-P(0)(OH)2, -(C2-4 alkoxy)-OΡίΟχΡ^'Χ, -Ci -4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments, the compound is of Formula (II j, wherein the compound is of Formula (II): LCQfrzn / zznz / q / viAi (II), LCQfrzn / zznz / q / viA or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof. In some aspects, the present invention provides a compound of Formula (III') R14 or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Wi,Xi, Yi, Zi, W2, X2, Y2, Z2, s, X3, X4X5, Xe, Xg. R3, R4R5, R6, R14, Ra, Rb, Rc, Rd, Re, Rf, R1, and R are, each independently, as defined in Formula (IA'); when s is 0, RC1 is as defined in Formula (IA); when s is 1, Wi and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D taken together with RC1 and RC2 forms a link group, where D is as defined in the Formula (IA'); R16 is absent, or is H, halogen, or C1-4 alkyl; R15 and R17, each independently, are absent, or are H, cyclopropyl, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORG, -NRcRd , -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; or R15and R19 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; R18 and R19 are, each independently, as defined herein; or R17 and R18 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; and Ro and Rh are each independently, as defined in Formula (IA j or Ra and Rh taken together with the atom(s) through which they are connected, form a 5-6 membered ring; and provided that at least one of (i), (ii), or (iii): (i) when (a) Ζι, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Ζι, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or X9is N; or (ii) when s is 0, (a) Ζι, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Ζι, Z2, Y1 and Y2 are each C, then R14 is a C1-4 alkyl substituted with halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd , -SO2NRcRd, and -OCONRcRden where Rces H; or (iii) when s is 0, (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Xb, and X9 is N and RA1 or RA2 is halogen, hydroxyl, optionally substituted (C1-6 alkyl), (C1-6 substituted alkyl)oxy¡-, optionally substituted (C1-6 alkyl)amino-, or optionally substituted (C1-6 alkyl)(Ci-4 alkyl)amino-, wherein the (O-e alkyl) of said (C1-6 alkyl) ) optionally substituted, (C1-6 alkyl)oxy¡- substituted, (O-b alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted is optionally substituted with 1-4 substituents, each independently selected from the group hydroxyl, -O-P(O)(OH)2, -O-P(O)(RIR)2, -N(Re)(Rf), CO^R*), -CONÍReXRj, optionally substituted phenyl , and optionally substituted 5-6 membered heteroaryl, wherein said optionally substituted phenyl, or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH )2, -O-P(O)(R'R)2, amino, (Ci-6alkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino, -(C1-6 alkyl)-NH2, halo (Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-OP(O)(R'R )2, halo(Ci-4alkoxy)-, C1-4alkoxy-, hydroxy-(C2-4alkoxy)-, -(C2-4alkoxy)-0-P(0)(OH)2, -(C2- 4-alkoxy)-OP(O)(R'R)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments, the compound is of Formula (III j, wherein the compound is of Formula (III): LCQfrzn / zznz / q / viAi R14 LCQfrzn / zznz / q / viAi or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof. In some aspects, the present invention provides a compound of Formula (IVj R14 or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Wi.Xi, Yi, Zi, W2, X2, Y2, Z2, r, s, X3, X4X5, X6, X9. R3, R4R5, R6, R14, R18, R19, Ra, Rb, Rc, Rd, Re, Rf, R1, and R are each independently when r is 0, RB1 and RB2 are each independently as defined in Formula (lAj; when s is 0, RC1 is as defined in Formula (IA'); when r is 1, RB1 and RB2 are, each independently, -CH2-, and B, taken together with RB1 and RB2, forms a bonding group, where B is a bond or B is as defined in Formula (lAj; when s is 1, Wi and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D taken together with RC1 and RC2 forms a link group, where D is as defined in the Formula (lAj; R16 is absent, or is H, halogen, or C1-4 alkyl; R15 and R17, each independently, are absent, or are H, cyclopropyl, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd , -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; or R15and R19 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; and Ro and Rh are each independently, as defined in Formula (IA j or Ra and Rh taken together with the atom(s) through which they are connected, form a 5-6 membered ring. In some embodiments, the compound is of Formula (IVj, where the compound is of Formula (IV): LCQfrzn / zznz / q / viAi (IV), or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof. In some embodiments, the compound is of Formula (Vj: R14 or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Υι, Y2, Z1 and Z2 are each independently O, S, Co N; Χι, X2, W1 and W2 are each independently CoN; X3 and Χ4 are each independently S or NRf; X5es N or CRA2; X6es N or CRA1; XgesNo CH; R3 and R5 are each independently -CON(Rd)(Rj, -CH2N(Rd)(R*), -N(Rd)(Rf), -N(Rd)CO(R*), -CH2N(Rd) CO(Rf) or one of R3 and R5 is -CON(Rd)(Rf), -CH2N(Rd)(Rf), -N(Rd)(Rf), -N(Rd)CO(Rf) or C^N^ CCKRf), and the other of R3 and R5 is H, -COOH, or -CO2RC; Rces C1-4 alkyl; RA2y raison cac|a each independently, H, halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, optionally substituted (C1-6 alkyl), or optionally substituted (Ci-6alkyl)oxy¡-, wherein the Ci- β alkyl of said optionally substituted (C1-6 alkyl), or optionally substituted (C1-6 alkyl)oxy is optionally substituted with 1-4 substituents, each independently selected from the group consisting of hydroxyl, C1-4 alkoxy, -N( R®)(Rf), CO2(Rf), -ΟΟΝ^®)^, and -COOH; each R is independently H, hydroxy, or C1-4 alkyl; Rese selected from H, (C1-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), and -CO2(Ci-4 alkyl); each Rfes independently H, hydroxyl, or (C1-4alkyl); R14 and RC2 are each independently absent, or are C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORG, -NRcRd, -COzR0, CONRcRd, -SO2NRcRd, and -OCONRcRd; R16 and RC1 are each independently absent, or are H or C1-4 alkyl; and R15, R17, R18, or R19 are each independently absent, or are H, C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2Rc, -CONRcRd, -SO2NRcRd, and -OCONRcRd; provided that at least one of (i), (¡i), or (iii) applies: (i) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or X9 is N; or (i) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C, then R14 is a C1-4 alkyl substituted with halogen, -ORC, -NRcRd, -CO2Rc, -CONRcRd, - SO2NRcRd, and -OCONRcRden where Rces H; or (iii) when (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Xe, and Xg is N and RA1 or RA2 is halogen, hydroxyl, optionally substituted (C1-6 alkyl), (C1-6 alkyl )oxy-substituted, (Ci e alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, LCQfrzn / zznz / q / YiAi wherein the C1-6 alkyl of said optionally substituted (C1-6 alkyl) or (Cíe alkyl)oxy¡- substituted is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxyl, -Ν^θ)^, -CC^RD, -CON^XRf), and -COOH. In some embodiments, the compound is of Formula (Vj, wherein the compound is of Formula (V): LCQfrzn / zznz / q / YiAi R14 or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof. In some aspects, the present invention provides a compound of Formula (lj or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Υι, Y2, Z1, and Z2 are each independently O, S, C, or N; Χι, X2, W1, and W2 are each independently C or N; RA1 and ra2 are each independently, H, halogen, hydroxyl, -O-P(O)(OH)2, -OPfOXR'RHX, -N(Re)(Rf), -CO2Rf, -N(Rf)CORb, -N( R9)SO2(Ci-4 alkyl)-N(Re)(R^, -N(R9)CO(Ci-4 alkyl)N(Rh)(Rf), (C1-6 alkyl) optionally substituted, (Cíe alkyl )oxy¡- optionally substituted, (C1-6 alkyl)amino- optionally substituted, and (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the (C1-6 alkyl) of said (C1-6 alkyl) ) optionally substituted, optionally substituted (C1-6 alkyl)oxy, optionally substituted (C1-6 alkyl)amino- and optionally substituted (C1-6 alkyl)(Ci-4 alkyl)amino are optionally substituted with 1-4 substituents, each independently selected from hydroxyl, -O-P(O)(OH)2, -O-PfOjfR'R1^, C1-4 alkoxy-, -ΙψΡθχΡ1), ΟΟΣίΡ'), -CON(Re)(Rf), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH)2 , -O-P(O)(R'R)2, amino, (Ci-6alkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino, -(C1-6 alkyl)-NH2, halo(Ci -6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-OP(O)(R'R)2 , halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-0-P(0)(OH)2, -(C2-4 alkoxy)-OP(O)(R'R)2, and C1-4 alkoxy-(Ci-4 alkoxy)-; and provided that at least one of (i), (i), or (iii) applies: (i) when s is 0, r is 1, (a) Zi, Z2, Yi and Y2 are each N, Wi, W2, Xi and X2 are each C; or (b) Wi, W2, Xi and X2 are each N, Zi, Z2, Yi and Y2 are each C; or (c) Zi and Yi are each N, Wi and Xi are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) Wi and Xi are each N, Zi and Yi are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or Xs is N; or (ii) when s is 0, r is 1, (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and SO2NRcRd, and -OCONRcRden where Rces H; or (iii) when s is 0, r is 1, (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2and Y2are each N, W2and X2are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Xe, and - substituted, (C1-6 alkyl)amino- optionally substituted, or (Ove alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the (Cí e alkyl) of said (Cí e alkyl) optionally substituted, (C1 -6 alkyl)ox¡- substituted, (C1-6 alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted is optionally substituted with 1-4 substituents, each independently selected between the hydroxyl group, -O-P(O)(OH)2, -O-P(O)(R'R)2, -N(Re)(Rf), COXRO, -CON(Re)(Rf), optionally substituted phenyl , and optionally substituted 5-6 membered heteroaryl, wherein said optionally substituted phenyl, or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH )2, -O-PIOXR'R^ amino, (C1-6 alkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino-, -(C1-6 alkyl)-NH2, halo(Ci- 6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl-O-PCOXR'R1^, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4alkoxy)-, -(C2-4alkoxy)-O-P(O)(OH)2, -(C2-4alkoxy)-O-P(O)(RlR)2 , C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-. In some aspects, the present invention provides a compound of Formula (Γ) or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: RA1 and RA2 are, each independently, H, halogen, hydroxyl, -N^XRf), -CO2Rf, N(Rf)CORb, -N(R9)SO2(Ci-4 alkyl)-N(Re)(R<), -N(R9)CO(Ci-4 alkyl)-N(Rh)(Rf), (C1-6 alkyl) optionally substituted, (C1-6 alkyl)ox¡- optionally substituted, (C1-6 alkyl)amino- optionally substituted, and (C1-6 alkyl)(Ci-4 alkyl)amino-optionally substituted, wherein the (C1-6 alkyl) of said optionally substituted (C1-6 alkyl), (C1-6 alkyl)oxyoptionally substituted, (C1-6 alkyl)amino-optionally substituted and (Ci-β alkyl)(Ci-4 alkyl)aminooptionally substituted is optionally substituted with 1-4 substituents, each independently selected from hydroxyl, C1-4 alkoxy-, -N^ Xro, -co2 (RF), -ον (ρ®) (ρ0, optionally substituted phenyl, and heteroarl group of 5-6 options optionally replaced, where said optionally optionally replaced or heteroaril of 5-6 members is optionally replaced with 1 -4 substituents, each independently selected from halogen, hydroxyl, amino, (C1-6 alkyl)amino-, (Cvs alkyl)(Ci-6 alkyl)amino-, halo(Ci-6 alkyl), hydroxy-(Ci- 4 alkyl)-, halo-(Ci-4 alkoxy)-, C14 alkoxy-, hydroxy-(C2-4 alkoxy)-, and C1-4 alkoxy-(Ci-4 alkoxy)-; LCQfrzn / zznz / q / viAi when r is 0, RB1 and RB2 are each independently H, Ci-e optionally substituted alkyl, halo(Ci6 alkyl), optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, C3- optionally substituted 6-cycloalkyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 910-membered heteroaryl, wherein said optionally substituted Ci-β alkyl, optionally substituted C2-6 alkenyl substituted, optionally substituted C2-6 alkynyl, optionally substituted C3s cycloalkyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl is optionally substituted with 1 -4 substituents each independently selected from halogen, nitro, -Rc, OH, -ORC, -NHZ, -NRCRC, -NRcRd, -OCORC, -CO2H, -CO2RC, -SORC, -SO2RC, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc; when r is 1, RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and RB2, forms a linking group, where B is a bond or B is -halo(Ci-io alkyl)-, -C1-10 optionally substituted alkyl, -C2-10 optionally substituted alkenyl-, -C2-10 optionally substituted alkynyl-, -C1-6 alkyl-O-Ci-6 optionally substituted alkyl-, -Ci-β alkyl-NRa-Ci -6-optionally substituted alkyl-, optionally substituted C3-6 cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, -C1-4 alk¡I(C3-6 cycloalkyl)- C1-4 alkyl- optionally substituted, -C1-4 alkyl-phenyl-Ci-4 alkyl- optionally substituted, -C1-4 alkyl-(4-6 membered heterocycloalkyl)-Ci-4 alkyl- optionally substituted, or -C1 -4-alkyl-(5-6 membered heteroaryl)-Ci-4-optionally substituted alkyl-, wherein the alkyl moiety of said -C1-10 optionally substituted alkyl-, -C2-10 optionally substituted alkenyl, -C2-10 alkynyl- optionally substituted, -Ci-e alkyl-O-Ci-s optionally substituted alkyl, -Ci-β alkyl-NRa-Ci-6 alkyl- optionally substituted, -C1-4 alkyl-(C3-6 cycloalkyl)-Ci 4 alkyl- optionally substituted, -C1-4 alkyl-phenyl-Optionally substituted C1-4 alkyl-, C1-4 alkyl-(4-6 membered heterocycloalkyl)-Optionally substituted Ci-4 alkyl-, or -Cu alkyl(5-6 heteroaryl optionally substituted member-Ci-4alkyl)- is optionally substituted with 1 or 2 substituents, each independently selected from halogen, halo(Ci-4alkyl), -OH, -ORC, -NH2, -NRcRd, -OCORC, - CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc, and remainder C3-e cycloalkyl, phenyl , 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl of said optionally substituted C3-bcycloalkyl, optionally substituted phenyl, optionally substituted 46-membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, -C1-4(C3)alkyl -6 cycloalkyl)-Ci-4 alkyl- optionally substituted, -C1-4 alkyl-phenyl-Ci-4 alkyl- optionally substituted, -C1-4 alkyl-(4-6 membered heterocycloalkyl)-Ci-4 alkyl- optionally substituted, or optionally substituted -C1-4 alkyl-(5-6 membered heteroaryl)-Ci-4 alkyl- is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxy, amino, (C1-4 LCQfrzn / zznz / q / viAi alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, C1 -4 alkoxy-, hydroxy-(C2-4 alkoxy)-, and C1-4 alkoxy-(Ci-4 alkoxy)-; when s is 1, W1 and Z2 are, each independently, C or N, RC1 and RC2 are each independently, -CH2-, and D taken together with RC1 and RC2, forms a linking group, where D is halo(Ci- i2 alkyl)-, -C112 alkyl- optionally substituted, -C2-i2alkenyl- optionally substituted, -Cz-iz alkynyl- optionally substituted, -Ci-β alkyl-O-Ci-e alkyl- optionally substituted, -Ci-β alkyl -NRa-Cie alkyl- optionally substituted, -C1-6 alkyl-(C3 6C¡cloalkyl)-Ci-6 alkyl- optionally substituted, -C1-6 alkyl-phenyl-Ci-6 alkyl- optionally substituted, -C1-6 optionally substituted alkyl-(4-6 membered heterocycloalkyl)-Ci-6 alkyl, or optionally substituted -C1-6 alkyl-(5-6 membered heteroaryl)-Ci-6 alkyl, wherein the alkyl moiety of said -C1-12 alkyl- optionally substituted, -C1-6 alkenyloptionally substituted, -C2-12 alkynyl- optionally substituted, -Ci-β alkyl-O-Ci-6 alkyloptionally substituted, -Ci-b alkyl-NRa-Ci-6 alkyl- optionally substituted, -C1-6 alkyl-(C3-6 cycloalkyl)-Ci-6 alkyl- optionally substituted, -Ci-β alkyl-phenyl-Ci-6 alkyl- optionally substituted, C1-6 alkyl-(heterocycloalkyl) 4-6 membered)-Ci-6 alkyl- optionally substituted, or -Ci-β alkyl(5-6 membered heteroaryl-Ci-6 alkyl optionally substituted is optionally substituted with 1 or 2 substituents, each independently selected from halogen, halo(Ci-4 alkyl), -OH, -ORC, NH2, -NRcRd, -OCORC, -CO2H, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, OCONH2, -OCONRcRd , -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc, and the Cs-ecycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said -Ci-β alkyl-(C3-6 cycloalkyl )-Ci-6 alkyl- optionally substituted, -C1-6 alkyl-phenyl-Ci-6 alkyloptionally substituted, -C1-6 alkyl-(4-6 membered heterocycloalkyl)-Ci-6 alkyl- optionally substituted, or -Ci -e alkyl-(5-6 membered heteroaryl)-Ci-e alkyl- optionally substituted is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (C1-4 alkyl)amino-, ( C1-4 alkyl)(Ci 4 alkyl)amino-, C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci~4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C24 alkoxy)-, and C1-4alkoxy-(Ci-4alkoxy)-; R4 and R6 are selected, each independently, from H, halogen, halo(Ci-s alkyl), halo(Ci-6 alkoxy)-, hydroxyl, -NH2, -NRCRC, -NRcRd, -CORC, -CO2RC, -N( Rd)CORc, -N(Rd)SO2Rc, N(R9)SO2(Ci-2alkyl)-N(Rh)(Rf), -N(R9)CO(Ci-2alkyl)-N(Rh)(Rf), (Ci-β alkyl) optionally substituted, (C16 alkyl)ox¡- optionally substituted, (Ci-β alkyl)amino- optionally substituted, and (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, where the (C1-6 alkyl) of said optionally substituted (C1-6 alkyl), (C1-6 alkyl)oxyoptionally substituted, (C1-5 alkyl)amino-optionally substituted and (C1-6 alkyl)(Ci-4 alkyl) aminooptionally substituted is optionally substituted with 1-4 substituents, each independently selected from the group -OH, -ORC, -NH2, -NRCRC, -NRcRd, -CO2H, -CO2RC, OCORC, -CO2H, -CO2Rc, -SORc, -SO2Rc-CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, -NRdSO2Rc, optionally substituted phenyl, optionally substituted 5-6-membered heterocycloalkyl, and 5-6-membered heteroaryl members optionally Substituted LCQfrzn / zznz / q / viAi, wherein said optionally substituted phenyl, 5-6 membered heterocycloalkyl, or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, C1-4 alkyl, halo(Ci-4 alkyl), hydroxy-(Ci-4 alkyl)-, halo(Ci -4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, C1-4 alkoxy-(Ci-4 alkoxy)-, -CORd, -CON(Rd)(Rf), and -CO2Rd ; each Rbes independently C1-4 alkyl, halo(Ci-4 alkyl), -(C1-4 alkyl)-OH, -(C1-4 alkyl)-O-(Ci4 alkyl), -(C1-4 alkylO-N^ XR'), -(Cu alkyl)-O-CO(Ci-4 alkyl), or -(C1-4 alkyl)-CO-O-(Ci-4 alkyl); each Rces independently H, C1-4 alkyl, halo(Ci-4 alkyl), -(C1-4 alkyl)-OH, -(C1-4 alkyl)-O(C1-4 alkyl), -(C1-4 alkyl -N^XRO, -(C1-4 alkyl)-O-CO(Ci-4 alkyl), -(C1-4 alkyl)-CO-O-(Ci-4 alkyl), C3-6 optionally substituted cycloalkyl, phenyl optionally substituted, optionally substituted 4-6-membered heterocycloalkyl, optionally substituted 5-6-membered heteroaryl, optionally substituted 9-10-membered heteroaryl, -C1-4 alkyl-C3-6cycloalkyl optionally substituted, -C1-4 alkyl-phenyl optionally substituted, -C1-4 optionally substituted 4-6 membered alkylheterocycloalkyl, -optionally substituted -C1-4 5-6 membered alkylheteroaryl, or -optionally substituted -C1-4 9-10 membered alkylheteroaryl, wherein the C3-6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl or 9-10 membered heteroaryl moiety of said optionally substituted C3-6 cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl -C1-4 alkylheterocycloalkyl 6-membered optionally substituted, -C1-4 optionally substituted 5-6-membered alkylheteroaryl, or -C1-4 optionally substituted 9-10 membered alkylheteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen , hydroxyl, amino, -(C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, C1-4 alkyl, halo(Ci-4 alkyl), halofCw alkoxy)-, C1- 4 alkoxy-, hydroxy-(C2 4alkoxy)-, C1-4 alkoxy-(Ci-4 alkoxy)-, -CORd, -CONfR^fR1), and -CO2Rd; and each Rees independently H, (C1-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), -CO2(Ci-4 alkyl), -CO-(5-6 heterocycloalkyl optionally substituted), -CO-(Ci-4 alkyl)-(56-membered heterocycloalkyl optionally substituted), -CO-(5-6 membered heteroaryl optionally substituted), -CO-(Ci-4 alkyl)(5-6 membered heteroaryl) optionally substituted member), wherein the optionally substituted 5-6 membered heterocycloalkyl or optionally substituted 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (C1-4 alkyl) amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2 -4 alkoxy)-, C1-4 alkoxy(C1-4 alkoxy)-, -CORd, -CON(Rd)(Rf), and -CO2Rd; provided that at least one of (i), (i), or (iii) applies: (i) when s is 0, r is 1, (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 LCQfrzn / zznz / q / viAi are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or X9 is N; or (¡i ) when s is 0, r is 1, (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and -SO2NRcRd, and -OCONRcRden where Rces H; or (iii) when s is 0, r is 1, (a) Z1 and Y1 are each N, W1 and Xi are each C; or (b) Zz and Y2 are each N, Wz and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Xs, and substituted, (C1-6 alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the (C1-6 alkyl) of said (C1-6 alkyl) optionally substituted , (Ci-β alkyl)oxy- substituted, (C1-6 alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted is optionally substituted with 1-4 substituents, each one independently selected from the group hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, N(Re)(R*), -CO^RO, -CONfR^fRi), optionally substituted phenyl, and optionally substituted 5-6 membered heteroaryl, wherein said optionally substituted phenyl, or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O )(OH)2, -O-P(O)(R'R)2, amino, (Ci-6alkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino, -(C1-6 alkyl)- NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-OP(O)( R'R)2, halo(Ci-4alkoxy)-, C1-4alkoxy-, hydroxy-(C2-4alkoxy)-, -(C2-4alkoxy)-0-P(0)(OH)2, - (C2-4alkoxy)-OP(O)(R'R)2, -C1-4alkyl-(Ci-4alkoxy), and C1-4alkoxy-(Ci-4alkoxy)-. Alternative definitions for the various groups and groups of substituents of Formula (I j, Formula (lAj, Formula (llj, Formula (lllj, Formula (IVj, or Formula (Vj) given throughout the specification are intended to describe each species of compounds described herein, individually, as well as groups of one or more species of compounds. The scope of this invention includes any combination of these definitions of groups and groups of substituents. The compounds of the invention are only those that are contemplated as chemically stable as will be appreciated by persons skilled in the art. Those skilled in the art will appreciate that the compounds of this invention may exist in other tautomeric forms including zwitterionic forms, or isomeric forms. All tautomeric (including zwitterionic forms) and isomeric forms of the formulas and compounds described herein are intended to be encompassed within the scope of the present invention. Those skilled in the art will also appreciate that the compounds of this invention may exist in tautomeric forms including, but not limited to, Formula (A), Formula (B), Formula (C), Formula (D) and / or Formula (E) or zwitterionic forms including, but not limited to, Formula (F), Formula (G), or Formula (H): LCQfrzn / zznz / q / YiAi LCQfrzn / zznz / q / viAi In some embodiments, when r is 1 and s is 0 (the total of r and s is I), the compound of the invention is a compound of Formula (l-Bj or Formula (l-bj: R14 (l-Bj (l-bj where X7 and Xs are each independently C=O or CH2. In some embodiments, the compound of the invention is a compound of Formula (IBj or Formula (l-bj where Xs is CR4. In some embodiments, when r is 0 and s is 1 (the total of r and s is I), W1 and Z2 are each independently C or N, the compound of the invention is a compound of Formula (l-D j or Formula ( l-dj: LCQfrzn / zznz / q / viAi (l-Dj (l-dj where X? and Xa are, each independently, C=O or CH2. In some embodiments, the compound of the invention is a compound of Formula (ΙΟ') or Formula (l-dj where X9 is CR4. In some embodiments, when r is 1 and s is 1 (the total of r and s is 2), W1 and Z2 are each independently C or N, the compound of the invention is a compound of Formula (l-BDj or Formula (l-bd j: (l-BD) (l-bd) where X7 and Xa are, each independently, C=O or CH2. In some embodiments, the compound of the invention is a compound of Formula (IBD j or Formula (l-bd j where Xg is CR4. It is to be understood that, for a compound of Formula (Ij, Formula (lAj, Formula (IIj, Formula (lllj, Formula (IVj, or Formula (Vj, where applicable): In some embodiments, W1, X1, Y1, Z1, W2, X2, Y2, and Z2 are each independently O, S, C, or N. In some embodiments, W1X1, Y1, and Z1 are each independently O, S, C, or N. In some embodiments, Wi, Xi, Yi, and Zi are each independently O, C, or N. In some embodiments, Wi, Xi, Yi, and Zi are each independently S, C, or N. In some embodiments, Wi,Xi, Yi, and Zi are each independently O, S, or C. In some embodiments, Wi.Xi, Yi, and Zi are each independently Or are. In some embodiments, Wi is O, S, C, or N. In some embodiments, Wi is O. In some embodiments, Wi is S. In some embodiments, Wi is C. In some embodiments of realization, Wi is N. In some embodiments, Xi is O, S, C, or N. In some embodiments, Xi is O. In some embodiments, Xi is S. In some embodiments, Xi is C. In some embodiments of realization, Xi is N. In some embodiments, Yi is O, S, C, or N. In some embodiments, Yi is O. In some embodiments, Yi is S. In some embodiments, Yi is C. In some embodiments of realization, Yi, is N. In some embodiments, Zi is O, S, C, or N. In some embodiments, Zi is O. In some embodiments, Zi is S. In some embodiments, Zi is C. In some embodiments of realization, Zi is N. In some embodiments, W2, X2, Y2, and Z2 are each independently O, S, C, or N. In some embodiments, W2, X2, Y2, and Z2 are each independently O, C, or N. In some embodiments, W2, X2, Y2, and Z2 are each independently S, C , or N. In some embodiments, W2, X2, Y2, and Z2 are each independently O, S, or C. In some embodiments, W2, X2, Y2, and Z2 are each independently , Or are. In some embodiments, W2 is O, S, C, or N. In some embodiments, W2 is O. In some embodiments, W2 is S. In some embodiments, W2 is C. In some embodiments, W2 is no. In some embodiments, X2 is O, S, C, or N. In some embodiments, X2 is O. In some embodiments, X2 is S. In some embodiments, no. In some embodiments, Y2 is O, S, C, or N. In some embodiments, Y2 is O. In some embodiments, Y2 is S. In some embodiments, Y2 is C. In some embodiments, Y2 is no. In some embodiments, Z2 is O, S, C, or N. In some embodiments, Z2 is O. In some embodiments, Z2 is S. In some embodiments, Z2 is C. In some embodiments, Z2 is no. In some embodiments, X3 and X4 are each independently S or NRf. In some embodiments, X3 and X4 are each independently S. In some embodiments, X3 and X4 are each independently NRf. I CQb7n / 77n7 / =l / YIAI In some embodiments, X3 is S or NRf. In some embodiments, X3 is S. In some embodiments, X3 is NRf. In some embodiments, X4 is S or NRf. In some embodiments, X4 is S. In some embodiments, X4 is NRf. In some embodiments, r is 0 or 1. In some embodiments, r is 0. In some embodiments, r is 1. In some embodiments, s is 0 or 1. In some embodiments, s is 0. In some embodiments, s is 1. In some embodiments, p is 1 or 2. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, when r is 0, B is absent, and RB1 and RB2 are not connected. In some embodiments, when s is 0, D is absent, and RC1 and RC2 are not connected. In some embodiments of the compounds of the present invention, RA1 and RA2 are, each independently, H, halogen, hydroxyl, -N(Re)(Rj, -CO2Rf, -NÍRjCOR13, -N(Rg)SO2(Ci-4 alkyl)N(Re)(Rj, -N(R9)CO(Ci-4 alkyl)-N(Rh)(Rj, (C1-6 alkyl) optionally substituted, (C1-6 alkyl)oxyoptionally substituted, ( C1-6 alkyl)amino-optionally substituted, and (Ci-β alkyl)(Ci-4 alkyl)amino-optionally substituted, wherein the (C1-6 alkyl) of said optionally substituted (C1-6 alkyl), (Ci-β optionally substituted alkyl)oxy, optionally substituted (C1-6 alkyl)amino and optionally substituted (C1-6 alkyl)(Ci-4 alkyl)amino is optionally substituted with 1-4 substituents, each independently selected from hydroxyl, C1-4 alkoxy -, -NÍR^ÍRj, -CO2(Rf), -CON^XRj, optionally substituted phenyl, and optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (C1-6 alkyl)amino-, (Ci-β alkyl)(Ci e alkyl)amino-, halo(Ci-e alkyl), hydroxy-( Ci-4 alkyl)-, halo-(Ci-4 alkoxy)-, Cv 4 alkoxy-, hydroxy-(C2 4 alkoxy)-, and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments of the compounds of the present invention, RA1 and RA2 are each independently hydroxyl, (C1-6 alkyl) substituted, (C1-6 alkyl)oxy-substituted, (Ci-e alkyl)amino optionally substituted, and optionally substituted (C1-6 alkyl)(Ci-4 alkyl)amino-, wherein the (Ci-e alkyl) of said substituted (Ci-e alkyl) and (C1-6 alkyl)oxy-substituted is optionally substituted with 1-4 substituents each independently selected from -OP(O)(OH)2, -O-P(O)(R'R)2, optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-PÍOJÍR'R'jz, amino, ( Ci-6alkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino, -(C1-6 alkyl)-NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, - (C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-OP(O)(R'R)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4alkoxy)-, -(C2-4alkoxy)-0-P(0)(OH)2, -(C2-4alkoxy)-OP(O)(R'R)2, -C1- 4-alkyl-(Ci-4alkoxy), and C1-4alkoxy-(Ci-4alkoxy)-; LCQfrzn / zznz / q / viAi and the (C1-6 alkyl) of said (Ci-e alkyl)amino- optionally substituted and (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted is optionally substituted with 1- 4 substituents each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, -N(Re)(R*), -CO2(R*), CON( Re)(Rf), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (Ci-6alkyl)amino-, (O s alkyl)(Ci e alkyl)amino, -(Ci- e alkyl)-NH2, halo(Ci-e alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-OP (O)(R'R)2, halo(Ci-4alkoxy)-, Ci-4alkoxy¡-, hydroxy-(C2-4alkoxy)-, -(C2-4alkoxy)-0-P(0)(OH )2, -(C2-4alkoxy)-OP(O)(R'R)2, -C1-4alkyl-(Ci-4alkoxy), and C1-4alkoxy-(Ci-4alkoxy)-. In some embodiments of the compounds of the present invention, RA1 and RA2 are, each independently, H, halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, -N (Re)(Rf), -CO2Rf, NÍRjCORh, -N(Ra)SO2(Ci-4 alkylj-NÍR^CR*), -N(R9)CO(Ci-4 alkyl)-N(Rh)(Rf) , (Ci-B alkyl) optionally substituted, (C16 alkyl)ox¡- optionally substituted, (C1-6 alkyl)amino- optionally substituted, and (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, in wherein the (C1-6 alkyl) of said (C1-6 alkyl) optionally substituted, (C1-6 alkyl)oxyoptionally substituted, (C1-6 alkyl)amino-optionally substituted and (Ci-β alkyl)(Ci-4 alkyl )aminooptionally substituted is optionally substituted with 1-4 substituents, each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(R R)2, C1-4 alkoxy-, -NíR^íRj, CC^Rj, -CON^XRj, optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected among halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (Ci-6alkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino , -(C1-6 alkyl)-NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1- 4 alkyl)-OP(O)(R'R)2, halo(Ci~4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2 4 alkoxy)-, -(C2 4alkoxy)-0-P(0 )(OH)2, -(C2 4 alkoxy)-OPIOOXR'R^, and C1-4 alkoxy¡-(Ci~4 alkoxy). In some embodiments of the compounds of the present invention, RA1 and RA2 are, each independently, H, halogen, hydroxyl, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino -, (C1-4 alkyl), hydroxy(Ci-4 alkyl)-, amino(Ci-4 alkyl)-, (C1-4 alkyl)amino(Ci-4 alkyl)-, (C1-4 alkyl)(Ci -4 alkyl)amino(Ci-4 alkyl)-, C1-4 alkoxy, hydroxy(C2-4 alkoxy)-, amino(C2-4 alkoxy)-, (C1-4 alkyl)amino(C2-4 alkoxy)- , (C1-4 alkyl)(Ci-4 alkyl)amino(C2-4 alkoxy)-, 6-membered heterocycloalkyl-(Ci-4 alkyl)-, phenyl(Ci-4 alkoxy)-, (C1-4 alkyl) OCONH(Ci-4 alkyl)-, hydrox¡(Ci-4 alkyl)amino-, (C1-4 alkyl)CONH-, (C1-4 alkyl)CON(Ci-4 alkyl)-, -CO2H, - CO2(Ci-4 alkyl), amino(Ci-4 alkyl)CONH-, (C1-4 alkyl)amino(Ci-4 alkyl)CONH-, (C1-4 alkyl)(Oí-4 alkyl)amino( Gi-4 alkyl)CONH-, amino(Gi-4 alkyl)WITH(Ci-4 alkyl)-, (C1-4 alkyl)amino(Ci-4 alkyl)WITH(Ci-4 alkyl)-, hydroxy(Ci- 4 alkyl)CONH-, (C1-4 alkyl)(Ci-4 alkyl)amino(Ci-4 alkyl)WITH(Ci-4 alkyl)-, hydroxy(Ci-4 alkyl)WITH(Ci-4 alkyl)-, HO2C(Ci-4 alkoxy)-, (C1-4 alkoxy)OCO(Ci-4 alkoxy)-, H2NCO(Ci-4 alkoxy)-, (C1-4 alkyl)HNCO(Ci-4 alkoxy)-, (C1 -4 alkyl)(Ci-4 alkyl)NCO(Ci-4 alkoxy)-, andNHSO2(Ci-4 alkyl)-. LCQfrzn / zznz / q / viAi In some embodiments of the compounds of the present invention, RA1 and RA2 are each independently H, halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (C1-4 alkyl)amino-, (Ci-4 alkyl)(Ci-4 alkyl)amino-, (C1-4 alkyl), hydroxy(Ci-4 alkyl)-, amino(Ci-4 alkyl)-, ( C1-4 alkyl)amino(Ci4 alkyl)-, (C1-4 alkyl)(Ci-4 alkyl)amino(Ci-4 alkyl)-, C1-4 alkoxy-, hydroxy(C2-4 alkoxy)-, -( C2-4 alkoxy)-OP(O)(OH)2, -(C2-4 3ΐοοχί-Ο-Ρ(Ο)(Ρ'Ρ)2, amino(C2-4 alkoxy)-, (C1-4 alkyl) amino(C2-4 alkoxy)-, (C1-4 alkyl)(Ci-4 alkyl)amino(C2-4 alkoxy)-, 6-membered heterocycloalkyl-(Ci-4 alkyl)-, phenyl(Ci-4 alkoxy) -, (C1-4 alkyl)OCONH(Ci-4 alkyl)-, hydroxy(Ci-4 alkyl)amino-, -amino(Ci-4 alkyl)-O-P(O)(OH)2, -amino(Ci- 4 alkyl)O-P(O)(R'R)2, (C1-4 alkyl)CONH-, (C1-4 alkyl)CON(Ci-4 alkyl)-, -CO2H, -CO2(Ci-4 alkyl), amino(Ci-4 alkyl)CONH-, (C1-4 alkyl)amino(Ci-4 alkyl)CONH-, (C1-4 alkyl)(Ci-4 alkyl)amino(Ci-4 alkyl)CONH-, amino( Ci-4 alkyl)WITH(Ci-4 alkyl)-, (C1-4 alkyl)amino(Ci-4 alkyl)WITH(Ci-4 alkyl)-, hydroxy(Ci-4 alkyl)CONH-, -NHCO(Ci -4 alkyl)-O-P(O)(OH)2, -NHCO(Ci-4 alkyl)-O- P(O)(R'R)2, (C1-4 alkyl)(Ci-4 alkyl)amino( Ci-4 alkyl)WITH(Ci-4 alkyl)-, hydroxy(Ci-4 alkyl)WITH(Ci-4 alkyl)-, -(C1-4 alkyl)NCO(Ci-4 alkyl)-O-P(O)( OH)2, -(C1-4 alkyl)NCO(Ci-4 alkyl)-O-P(O)(R'R)2, HO2C(Ci-4 alkoxy)-, (C1-4 alkyl)OCO(Ci-4 alkoxy)-, H2NCO(Ci-4 alkoxy)-, (C1-4 alkyl)HNCO(Ci-4 alkoxy)-, (C1-4 alkyl)(Ci-4 alkyl)NCO(Ci-4 alkoxy)-, and NHSO2(Ci-4 alkyl)-. In some embodiments, RA1 and RA2 are, each independently, H, halogen, (C16 alkyl)ox¡-, hydroxy(C2-6 alkyl)ox¡-, HO(O)C-(C2-6 alkyl)ox¡ -, amino(C2-6 alkyl)ox¡-, hydroxyl, amino, or amino(Ci-4 alkyl)-. In some embodiments, RA1 and RA2 are each independently H, halogen, hydroxyl, (C1-6alkyl)ox¡-, hydroxy(C2-6alkyl)ox¡-, -(C2-4alkoxy)-0-P(0 )(OH)2, o-(C2-4 alkoxy)-0-P(0)(RlR)2. In some embodiments, RA1 and RA2 are each independently H. In some embodiments, RA1 and RA2 are each H. In some embodiments, RA1 and RA2 are each independently halogen. In some embodiments, RA1 and RA2 are each halogen. In some embodiments, RA1 and RA2 are each -OCH2CH2CH2NH2. In some embodiments, RA1 and RA2 are independently H, halogen, hydroxyl, OCH2CH2CH2OH, -OCH2CH2CH2COOH, -OCH2CH2CH2NH2, -OCH3, or -Ν(Ρθ)(Ργ In some embodiments of RA1 and RA2 is -OCHs and the other of RA1 and RA2 is halogen, -OH, OCH2CH2CH2OH, -OCH2CH2CH2COOH, -OCH2CH2CH2NH2, -OCH3, or -N(Re)(Rf). In some embodiments of RA1 and RA2 is H and the other of RA1 and RA2 is halogen, -OH, OCH2CH2CH2OH, -OCH2CH2CH2COOH, -OCH2CH2CH2NH2, -OCH3, or -N(Re)(Rf). In some embodiments of RA1 and RA2 is -OCHs and the other of RA1 and RA2 is -OCH2CH2CH2OH. In some embodiments of RA1 and RA2 is -OCH3 and the other of RA1 and RA2 is OCH2CH2CH2COOH. In some embodiments of RA1 and RA2 is H and the other of RA1 and RA2 is -OCH2CH2CH2OH. In some embodiments of RA1 and RA2 is -OCHs and the other of RA1 and RA2 is -OCH2CH2CH2NH2. In some embodiments of RA1y RA2 is -OH and the other of RA1y RA2 is -OCH2CH2CH2OH. LCQfrzn / zznz / q / viAi In some embodiments of RA1 and RA2 is -OH and the other of RA1 and RA2 is OCH2CH2CH2COOH. In some embodiments of RA1y RA2is -OH and the other of RA1y RA2is -OCH2CH2CH2NH2. In some embodiments, RA1 is H, halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, -OP(O)(OH)2, -O-P(O)(R'R)2, -N(Re )(Rf), -CO2Rf, -N(R1)CORb, -N(R9)SO2(Ci-4 alkyl)-N(R®)(Rf), -N(R0)CO(Ci4 alkyl)-N( Rh)(Rf), (C1-6 alkyl) optionally substituted, (C1-6 alkyl)oxy- optionally substituted, (C1-6 alkyl)amino- optionally substituted, and (C1-6 alkyl)(Ci 4 alkyl)amino - optionally substituted, wherein the (C1-6 alkyl) of said (Ove alkyl) optionally substituted, (C1-6 alkyl)oxyoptionally substituted, (C1-6 alkyl)amino-optionally substituted and (C1-6 alkyl)(Ci -4 alkyl)aminooptionally substituted is optionally substituted with 1-4 substituents, each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(RIR)2, C1-4 alkoxy-, -N (Re)(Rf), CCh / R1), -CON(Re)(Rf), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (Ci-6alkyl)amino-, ( C1-6 alkyl)(Ci-6 alkyl)amino, -(C1-6 alkyl)-NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P (O)(OH)2, -(C1-4 alkyl)-OP(O)(R'R)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy) -, -(C2-4alkoxy)-0-P(0)(OH)2, -(C2-4 alkoxy)-OP(O)(R'R)2, -C1-4 alkyl-(Ci-4 alkoxy ), and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments, RA1 is H. In some embodiments, RA1 is halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, -OP(O)(OH)2, -O-P(O)(R'R)2, -N(Re )(R*), -CO2Rf, -NCR^COR / -N(R9)SO2(Ci-4 alkyl)-N(R®)(Rf), -N(R9)CO(Ci4 alkylj-NCRbXR1), ( C1-6 alkyl) optionally substituted, (C1-6 alkyl)oxy- optionally substituted, (C1-6 alkyl)amino- optionally substituted, and (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, where the (C1-6 alkyl) of said (C1-6 alkyl) optionally substituted, (C1-6 alkyl)oxy-optionally substituted, (C1-5 alkyl)amino-optionally substituted and (C1-6 alkyl)(Ci 4 alkyl) )optionally substituted amino is optionally substituted with 1-4 substituents, each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P / OjíR'R1^, C14 alkoxy-, -Ν / ΡθχΡ1), CChCR1), -CON^XR1), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-PtOXR'R^ amino, (Ci-6alkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino, -(C1-6 alkyl) -NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-OP(O) (R'R)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-0-P(0)(OH)2 , -(C2-4 alkoxy)-OP(O)(R'R)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments, RA1 is halogen. In some embodiments, RA1 is F, Cl, Br, or I. In some embodiments, RA1 is F, Cl, or Br. In some embodiments, RA1 is F. In some embodiments, RA1 is Cl. embodiments, RA1es Br. LCQfrzn / zznz / q / viAi In some embodiments, RA1 is amino, amino(Ci-4 alkyl)-, hydroxyl, -O-P(O)(OH)2, -OP(O)(R'R)2, -Ν(Ρ®)(Ρ % -CO2Rf, -NÍROCOR», -N(R9)SO2(Ci-4 alkyl)-N(Re)(Rf), -N(R9)CO(Ci-4 alkyl)N(Rh)(R*), (Ci-6 alkyl)optionally substituted, (Ci-e alkyl)oxy¡- optionally substituted, (C1-6 alkyl)amino- optionally substituted, and (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the (Ci-e alkyl) of said optionally substituted (Ci-s alkyl), (Ci-s alkyl)oxy¡optionally substituted (Ci-e alkyl)amino- optionally substituted and (Ci-b alkyl)(Ci- Optionally substituted 4alkyl)amino is optionally substituted with 1-4 substituents, each independently selected from hydroxyl, -O-P(O)(OH)2, -O-PtOXR'R11)^ C1.4 alkoxy-, -N(Re) (Rf), CO2(R0, -CON^XR1), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(RIR)2, amino, (Ci-ealkyl)amino-, (Ci b alkyl)(Ci-6 alkyl )amino, -(C1-6 alkyl)-NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -( C1-4 alkyl)-OP(O)(R'R)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4alkoxy)-0 -P(0)(OH)2, -(C2-4 alkoxy)-OP(O)(R'R)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci -4 alkoxy)-. In some embodiments, RA1 is amino or amino(Ci-4 alkyl)-, wherein the (C1-6 alkyl) of said optionally substituted (C1-6 alkyl)amino- is optionally substituted with 1-4 substituents each independently selected from hydroxyl, O-P(O)(OH)2, -O-P(O)(R'RH)2, C1-4 alkoxy-, N(R®)(R*), -CO2(R*), -CON ^XRf), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (Ci-ealkyl)amino-, (C1-6 alkyl)(Ci-e alkyl)amino, -( C1-6 alkyl)-NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl) -OP(O)(R'R)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4alkoxy)-0-P(0) (OH)2, -(C2-4 alkoxy)-OΡ(Ο)(Ρ'Ρ)2, -Ci-4 alkyl-(Ci 4 alkoxy), and C1-4 alkoxy¡-(Ci~4 alkoxy)- . In some embodiments, RA1 is hydroxyl, -O-P(O)(OH)2, -O-PfOjfR'R1^, -NfR^fRf), CO2Rf, -NfRjCORf, -N(R9)SO2(Ci-4 alkyD- N^XRf), -N(R9)CO(Ci-4 alkylhN^XRf), (C1-6 alkyl) optionally substituted, (C1-6 alkyl)oxy- optionally substituted, (C1-6 alkyl)amino- optionally substituted , and (C1-6 alkyl)(Ci-4 alkyl)amino-optionally substituted, wherein the (C1-6 alkyl) of said (C1-6 alkyl) optionally substituted, (C1-6 alkyl)oxyoptionally substituted, (Ci-b alkyl)amino-optionally substituted and (Ci-e alkyl)(Ci-4 alkyl)amino-optionally substituted is optionally substituted with 1-4 substituents, each independently selected from hydroxyl, -O-P(O)(OH)2 , -O-P(O)(R R)2, C1-4 alkoxy-, -N(R®)(Rf), CO^Rf), -CON(Re)(Rf), optionally substituted phenyl, and a heteroaryl group of 5-6 membered optionally substituted, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P( O)(R'R)2, amino, (Ci-ealkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino, -(C1-6 alkyl)-NH2, halo(Ci -6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-O LCQfrzn / zznz / q / viAi P(O)(R'R)2, halo(Ci-4 alkoxy)-, Ci-4alkoxy¡-, hydroxy-(C2-4 alkoxy)-, -(C2-4alkoxy)-0-P(0)( OH)2, -(C2-4 alkoxy)-OP(O)(R'R)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments, RA1 is optionally substituted (C1-6 alkyl)oxy-, wherein the (C16 alkyl) of said optionally substituted (C1-6 alkyl)oxy- is optionally substituted with 1-4 substituents each independently selected between hydroxyl, O-P(O)(OH)2, -O-P(O)(R'R)2, C14 alkoxy-, -N(Re)(Rf), -CO2(Rf), -CON(Re)(Rf ), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P (O)(OH)2, -O-P(O)(R'R)2, amino, (C1-6 alkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino-, -(Cí e alkyl)-NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkylJ-O-PIOXR 'R^, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-O-P(O)(OH)2, -(C2- 4 alkoxy)-O-P(O)(RlR)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments, RA1 is (Ci s alkyl)oxy-substituted, wherein the (C1-6 alkyl) of said (C1-6 alkyl)oxy-substituted is substituted with 1-4 substituents each independently selected from hydroxyl, O-P(O)(OH)2, -O-P(O)(R'R)2, C1-4 alkoxy-, -Ν^χΡ*), -CO2(Rf), -CONÍR^ÍR1), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH) 2, -OP(O)(R'R)2, amino, (C1-6 alkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino-, -(Ci-e alkyl)-NH2, halo(Ci-e alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkylO-O-PIOjíR'R1^, halo (Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-O-P(O)(OH)2, -(C2-4alkoxy)-O-P( O)(RlR)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments, RA1 is (C1-6 alkyl)oxy-substituted, wherein the (C1-6 alkyl) of said (C1-6 alkyl)oxy-substituted is substituted with hydroxy. In some embodiments, RA1 is OCH2CH2CH2OH. In some embodiments, RA1 is hydroxy(C2 alkyl)oxy-. In some embodiments, RA1 is HO(O)C-(C2-6 alkyl)oxy-, In some embodiments, RA1 is -OCH2CH2CH2COOH. In some embodiments, RA1 is amino(C2-6 alkyl)oxy-. In some embodiments, RA1 is -OCH2CH2CH2NH2. In some embodiments, RA1 is (C1-6 alkyl)ox¡-. In some embodiments, RA1 is (methyl)oxy- (i.e., methoxy). In some embodiments, RA1 is -OH. In some embodiments, RA1 is amino. In some embodiments, RA1 is amino(Ci-4 alkyl)-. In some embodiments, RA2 and RA1 are, each independently, H, halogen, hydroxyl, amino, amino(Ci-4 alkyl)-, (Ci-β alkyl) optionally substituted, or (C1-6 alkyl)oxyoptionally substituted, in wherein the C1-6 alkyl of said optionally substituted (C1-6 alkyl), or optionally substituted (C1-6 alkyl)oxy is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, -O-P (O)(OH)2, C1-4 alkoxyl, LCQfrzn / zznz / q / viAi N(R®)(R*), -COOH, and optionally substituted phenyl, and each Rese independently selected from H, Ci-4 alkyl, -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), - (C1-4 alkyl)NH2, -(C1-4 alkyl)(Ci-4 alkoxy), and -CO2(Ci-4 alkyl). In some embodiments, RA2 and RA1 are each independently H, halogen, hydroxyl, amino, amino(Ci-4 alkyl)-, optionally substituted (Gis alkyl), or optionally substituted (Ci-s alkyl), and the Ci-b alkyl of said optionally substituted (Cí e alkyl), (Ci-e alkyl)oxyoptionally substituted is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, -O-P(O) (OH)2, -0^(0)^^)2, -Ν(Ρ®)(Ρ*), C1-4 alkoxy, phenyl, and optionally substituted 5-6 membered heteroaryl comprising at least one nitrogen u oxygen as a ring member, and each R® is selected, each independently, from H, C1-4 alkyl, -(C1-4 alkyl)NH2, and -(C1-4 alkyl)Ci-4 alkoxy. In some embodiments, at least one of RA2 or RA1 are, each independently, H, hydroxyl, halogen, amino, amino(Ci-4 alkyl)-, (Ci s alkyl) optionally substituted, or (Ci-b alkyl)ox optionally substituted, and the Ci-e alkyl of said (Ci-e alkyl) optionally substituted, (Ci-β alkyl)oxyoptionally substituted is optionally substituted with 1-4 substituents, each independently selected from -N^XRO, tetrahydropyran, pyrrolidinyl, piperazinyl, piperidyl and morpholinyl and each R® is selected, each independently, from H, C1-4 alkyl, -(C1-4 alkyl)NH2, and -(Ci-4 alkyl)Ci-4 alkoxy. In some embodiments, at least one of RA2 or RA1 are, each independently, H, hydroxyl, halogen, amino, amino(Ci-4 alkyl)-, (C1-6 alkyl) optionally substituted, or (O-e alkyl)oxy optionally substituted, and the Ci-ealkyl of said optionally substituted (Ci-b alkyl), (C1-6 alkyl)oxyoptionally substituted is optionally substituted with 1-4 substituents, each independently selected from tetrahydropyran, pyrrolidinyl, piperazinyl, piperidyl and morpholinyl , and each R® is selected, each independently, between H and C1-4 alkyl. In some embodiments, RA2 is H, halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, -OP(O)(OH)2, -O-PIOXR'R^ -N(R®)(Rf) , -CO2Rf, -N(Rf)CORb, -N(R9)SO2(Ci-4 alkyl)-N(R®)(Rf), -N(R9)CO(Ci4 alkyl)-N(Rh)(Rf ), (Ci-e alkyl) optionally substituted, (C1-6 alkyl)oxy- optionally substituted, (Ci b alkyl)amino- optionally substituted, and (Ci-β alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the (Ci-b alkyl) of said optionally substituted (Cib alkyl), (0-6 alkyl)oxyoptionally substituted, (Ci-b alkyl)amino-optionally substituted and (Ci-e alkyl)(Ci-4 alkyl) aminooptionally substituted is optionally substituted with 1-4 substituents, each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(RIRII)2, C1-4 alkoxy-, -N(R®) (Rf), CO2(Rf), -CON(R«)(Rf), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -0^(0)(^)2, amino, (Ci-6alkyl)amino-, (Ci b alkyl)(Ci-6 alkyl)amino, -(C1-6 alkyl)-NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O )(OH)2, -(C1-4 alkyl)-O P(O)(R'R)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4alkoxy)-0-P(0)( OH)2, -(C2-4 alkoxy)-OP(O)(R'R)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments, RA2 is H. In some embodiments, RA2 is halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, -OP(O)(OH)2, -O-P(O)(R'R)2, -N(R®) (Rf), -CO2Rf, -N(R1)CORb, -N(R9)SO2(Ci-4 alkyl)-N(Re)(Rf), -N(R9)CO(Ci4 alkyl)-N(Rh) (Rf), (C1-6 alkyl) optionally substituted, (C1-6 alkyl)oxy- optionally substituted, (C1-6 alkyl)amino- optionally substituted, and (C1-6 alkyl)(Ci 4 alkyl)amino- optionally substituted, wherein the (C1-6 alkyl) of said (C1-6 alkyl) optionally substituted, (C1-6 alkyl)oxyoptionally substituted, (C1-6 alkyl)amino-optionally substituted and (C1-6 alkyl) Optionally substituted (Ci-4 alkyl)amino is optionally substituted with 1-4 substituents, each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(RIR)2, C1-4 alkoxy-, -ΙψΡθχΡ1), CC^Rf), -CON(Re)(Rf), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (Ci-6alkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino, -(C1-6 alkyl)-NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O) (OH)2, -(C1-4 alkyl)-OP(O)(R'R)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, - (C2-4alkoxy)-0-P(0)(OH)2, -(C2-4 alkoxy)-OΡίΟχΡ^'Χ, -Ci-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-( Ci-4 alkoxy)-. In some embodiments, RA2 is halogen. In some embodiments, RA2 is F, Cl, Br, or I. In some embodiments, RA2 is F, Cl, or Br. In some embodiments, RA2 is F. In some embodiments, RA2 is Cl. embodiments, RA2es Br. In some embodiments, RA2 is amino, amino(Ci-4 alkyl)-, hydroxyl, -O-P(O)(OH)2, -OP(O)(R'R)2, -N(Re)(Rf) , -CO2Rf, -NCRjCOR1 / -N(R9)SO2(Ci-4 alkyl)-N(Re)(Rf), -N(R0)CO(Ci^ alkyl)N(Rh)(R*), (C1 -6 alkyl) optionally substituted, (Ci-β alkyl)oxy- optionally substituted, (C1-6 alkyl)amino- optionally substituted, and (C1-6 alkyl)(Ci 4 alkyl)amino- optionally substituted, wherein ( C1-6 alkyl) of said (Cve alkyl) optionally substituted, (C1-6 alkyl)oxyoptionally substituted, (C1-6 alkyl)amino-optionally substituted and (C1-6 alkyl)(Ci-4 alkyl)aminooptionally substituted is optionally substituted with 1-4 substituents, each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, C1-4 alkoxy-, -ΙψΡθχΡ1), CC^RO, -CON(Re)(Rf), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected between halogen, hydroxyl, -O-P(O)(OH)2, -O-PIOXR'R^ amino, (Ci-6alkyl)amino-, (C16 alkyl)(Ci-6 alkyl)amino, -(C1-6 alkyl )-NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-OΡίΟχΡ^' Χ, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4alkoxy)-0-P(0)(OH)2, -(C2-4 alkoxy)-OΡίΟχΡ^'Χ, -Ci-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments, RA2 is amino or amino(Ci-4 alkyl)-, wherein the (C1-6 alkyl) of said optionally substituted (C1-6 alkyl)amino- is optionally substituted with 1-4 substituents each. LCQfrzn / zznz / q / viAi one independently selected from hydroxyl, O-P(O)(OH)2, -O-P(O)(R'R)2, C1-4 alkoxy-, ΙψΡθχΡ1), -ΟΟς / Ρ1), - CON(Re)(Rf), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (Ci-6alkyl)amino-, (Ci-s alkyl)(Ci-6 alkyl)amino, -(Ci-6 alkyl)-NH2, halo(Ci-e alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-OΡ(Ο)(Ρ'Ρ)2, halo(Ci-4 alkoxy)-, Cu alkoxy-, hydroxy-(C2 4 alkoxy)-, -(C24alkoxy¡)-0-P(0)(OH )2, -(C2 4 alkoxy)-OP(O)(RiR)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments, RA2 is optionally substituted (C1-6 alkyl)oxy¡-, wherein the (C1-6 alkyl) of said optionally substituted (C1-6 alkyl)oxy- is optionally substituted with 1-4 substituents each independently selected between hydroxyl, O-P(O)(OH)2, -O-P(O)(RIR)2, C14 alkoxy-, -N(Re)(Rf), -CO^Rj, -CON(Re)(Rf), phenyl optionally substituted, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O) (OH)2, -O-P(O)(R'R)2, amino, (C1-6 alkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino-, -(C16 alkyl)-NH2 , halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 3^υϋ)-Ο-Ρ( Ο)(Ρ'Ρ)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-O-P(O)(OH)2 , -(C2-4 alkoxyj-O-PÍOJÍR'R1^, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments, RA2 is (Ci-e alkyl)oxy-substituted, wherein the (C1-6 alkyl) of said (C1-6 alkyl)oxy- substituted is substituted with 1-4 substituents each independently selected from hydroxyl, O-P(O)(OH)2, -O-P(O)(R'R)2, C1-4 alkoxy-, -N(Re)(R*), -CO2(Rj, -CONCRg / R1), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxy, -O-P(O )(OH)2, -OΡ(Ο)(Ρ'Ρ)2, amino, (Ove alkyl)amino-, (Ove alkyl)(Ci e alkyl)amino-, -(C1-6 alkyl)-NH2, halo (Ci-e alkyl), hydroxy-(Ci 4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(Cu alkylXO-P / OXR'R11)^ halo(Ci-4 alkoxy)-, C1-4alkoxy-, hydroxy¡-(C2-4alkoxy)-, -(C2-4alkoxy)-O-P(O)(OH)2, -(C2-4alkoxy)-O-P(O)( RlRll)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments, RA2 is (Ci-e alkyl)oxy-substituted, wherein the (C1-6 alkyl) of said (C1-6 alkyl)oxy-substituted is substituted with hydroxy. In some embodiments, RA2 is OCH2CH2CH2OH. In some embodiments, RA2 is hydroxy(C2-6 alkyl)oxy-. In some embodiments, RA2 is HO(O)C-(C2-6 alkyl)oxy-, In some embodiments, RA2 is -OCH2CH2CH2COOH. In some embodiments, RA2 is amino(C2-6 alkyl)oxy-. In some embodiments, RA2 is -OCH2CH2CH2NH2. In some embodiments, RA2 is (C1-6 alkyl)oxy-. In some embodiments, RA2 is (methyl)oxy- (i.e., methoxy). In some embodiments, RA2 is -OH. In some embodiments, RA2 is amino. LCQfrzn / zznz / q / viAi In some embodiments, RA2 is amino(Ci-4 alkyl)-. In some embodiments, r is 0 and RB1 and RB2 are each independently H, Ci^ optionally substituted alkyl, halo(Ci-6 alkyl), optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, C3-6 optionally substituted cycloalkyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl, wherein said Cve is optionally substituted alkyl, C2e optionally substituted alkenyl, C2e optionally substituted alkynyl, optionally substituted C3-6 cycloalkyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, nitro, -Rc, OH, -ORC, -NHZ, -NRCRC, -NRcRd, -OCORC, -CO2H, -CO2RC, -SORC, -SO2RC, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc. In some embodiments, r is 0 and RB1 and RB2 are each H. In some embodiments, r is 0 and RB1 and RB2 are each independently H, optionally substituted C1-6 alkyl, halo(Ci-6 alkyl), optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, C3- optionally substituted 6-cycloalkyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-membered heteroaryl. In some embodiments, s is 0, W1 and Z2 are each independently C or N, and RC1 is absent, or is H, halogen, or C1-4 alkyl and RC2 is absent or is optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl group is optionally substituted with a substituent selected from -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments of the compounds of this invention, when s is 0, W1 and Z2 are each independently C or N, and RC1 and RC2 are each independently absent, or are H or C1-4 alkyl. In some embodiments, when s is 0, W1 is C, RC1 is C1-3 alkyl; specifically, methyl. In some embodiments, when s is 0, Z2 is C or N, RC2 is C1-3alkyl; specifically, methyl or ethyl. In some embodiments, when s is 0, Z2 is C or N, RC2 is ethyl. In some embodiments of the compounds of this invention, s is 0, W1 is C, Z2 is O or S, and RC1 is absent, or is H, halogen, or C1-4 alkyl and RC2 is absent. In some embodiments of the compounds of this invention, when s is 0, W1 is C, Z2 is O or S, and RC1 is absent, or is H or C1-4 alkyl and RC2 is absent. In some embodiments, when s is 0, W1 is C, RC1 is C1-3 alkyl; specifically, methyl. In some embodiments, when s is 0, Z2 is O or S, RC2 is C1-3 alkyl; specifically, methyl or ethyl. In some embodiments, when s is 0, Z2 is O or S, RC2 is ethyl. In some embodiments of the compounds of this invention, res1 and RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and RB2, forms a linking group, where B is a bond or B is -halo(Ci-io alkyl)-, -C1-10 alkyl- optionally substituted, -C2-io alkenyl CQbzn / zznz / zi / YiAi optionally substituted, -C2-10 alkynyl- optionally substituted, -C1-6 alkyl-O-Ci-6 alkyloptionally substituted, -C1-6 alkyl-NRa-Ci-6 alkyl- optionally substituted, C3 -6 optionally substituted cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, -optionally substituted -C1-4 alkyl-(C3-6 cycloalkyl)-Ci-4 alkyl, - C1-4 alkyl-phenyl-Ci-4 alkyl- optionally substituted, C1-4 alkyl-(4-6 membered heterocycloalkyl)-Ci-4 alkyl- optionally substituted, or -C1-4 alkyl(5-6 membered heteroaryl) )-Ci-4 alkyl- optionally substituted, wherein the alkyl moiety of said -C1-10 alkyl- optionally substituted, -C2-10 alkenyl-optionally substituted, -C2-10 alkynyl- optionally substituted, -C1-6 alkyl-O- Ci-6 alkyl optionally substituted, -C1-6alkyl-NRa-Ci-6 alkyl- optionally substituted, -Ci-4alkyl-(C3-6 cycloalkyl)C1-4 alkyl- optionally substituted, -C1-4 alkyl-phenyl-Ci- 4 alkyl- optionally substituted, -C1-4 alkyl(4-6 membered heterocycloalkyl)-Ci-4 alkyl- optionally substituted, or -C1-4 alkyl-(56 membered heteroaryl-Ci-4 alkyl)- optionally substituted optionally substituted with 1 or 2 substituents, each independently selected from halogen, halo(Ci-4 alkyl), -OH, -ORC, -NH2, -NRcRd, OCORC, -CO2H, -CO2Rc, -SORc, -SO2Rc-CONH2 , -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc, and the C3-6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-membered heteroaryl moiety 6 members of said C3-6 optionally substituted cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, -C1-4 alkyl-(C3-6 cycloalkyl)-Ci-4 alkyl - optionally substituted, -C1-4 alkyl-phenyl-Ci-4 alkyl- optionally substituted, C1-4 alkyl-(4-6 membered heterocycloalkyl)-Ci-4 alkyl- optionally substituted, or -C1-4 alkyl optionally substituted (5-6 membered heteroaryl)-Ci-4 alkyl- is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (C1-4 alkyl)amino-, (C1-4 alkyl )(Ci-4 alkyl)amino-, -C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, -C1-4 alkoxy-, hydroxy-(C2 4 alkoxy)-, and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments of the compounds of this invention, r is 1 and RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and RB2, forms a linking group, where B is a bond or B is -halo(Ci-io alkyl)-, -C1-10 alkyl- optionally substituted, -C2-10 alkenyl optionally substituted, -C2-10 alkynyl- optionally substituted, -C1-6 alkyl-O-Ci-6 alkyl optionally substituted , -C1-6 alkyl-NRa-Ci-6 alkyl- optionally substituted, C3-6 optionally substituted cycloalkyl, optionally substituted phenyl, optionally substituted 4-6-membered heterocycloalkyl, optionally substituted 5-6-membered heteroaryl, -C1-4 alkyl-(C3-6 cycloalkyl)-Ci-4 alkyl- optionally substituted, -C1-4 alkyl-phenyl-Ci-4 alkyl- optionally substituted, C1-4 alkyl-(4-6 membered heterocycloalkyl)-Ci -4 alkyl- optionally substituted, or -C1-4 alkyl(5-6 membered heteroaryl)-Ci-4 alkyl- optionally substituted, wherein the alkyl moiety of said -C1-10 alkyl- optionally substituted, -C2-10 optionally substituted alkenyl, -C2-10 alkynyl- optionally substituted, -C1-6 alkyl-O-Ci-6 alkyloptionally substituted, -Ci-6alkyl-NRa-Ci-6alkyl- optionally substituted, -Ci-4alkyl-(C3-6cycloalkyl) LCQfrzn / zznz / q / YiAi Ci-4 alkyl- optionally substituted, -C1-4 alkyl-phenyl-Ci-4 alkyl- optionally substituted, -C1-4 alkyl(4-6 membered heterocycloalkyl)-Ci-4 alkyl- optionally substituted, or -C1- Optionally substituted 4-alkyl-(56-membered heteroaryl-Ci-4 alkyl)- is optionally substituted with 1 or 2 substituents, each independently selected from halogen, halo(Ci-4 alkyl), -OH, -O-P(O)( OH)2, -OP(O)(R'R)2,-ORC, -NH2, -NRcRd, -OCORC, -CO2H, -CO2RC, -SORC, -SO2RC, -CONH2, -CONRcRd, -SO2NH2, - SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRd, and NRdSO2Rc, and the C3.6cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said optionally substituted C3e cycloalkyl, optionally substituted phenyl, optionally substituted 4-6-membered heterocycloalkyl, optionally substituted 5-6-membered heteroaryl, -C1-4 alkyl-(C3-6 cycloalkyl)-Ci-4 alkyl- optionally substituted, -C1-4 alkyl-phenyl -Ci-4 alkyl- optionally substituted, C1-4 alkyl-(4-6 membered heterocycloalkyl)-Ci-4 alkyl- optionally substituted, or -C1-4 alkyl(5-6 membered heteroaryl) C1-4 alkyl- optionally substituted is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -OP(O)(R'R)2, amino, (C1-4 alkyl) amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, -C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, -C1-4 alkoxy-, hydroxy¡-(C2-4 alkoxy)-, and -C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments of the compounds of this invention, r is 1, RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and RB2, forms a 2-6 membered linking group. In another embodiment, res 1, RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and RB2, forms a 3-6 member linking group. In yet another embodiment, r is 1, RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and RB2, forms a 4-5 member linking group. In some embodiments, B is a link. In some embodiments, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -C1-10 alkyl- group or is a -C1-10 alkyl-, -C2-w alkenyl- group. , -C2-w alkynyl-, -Ci-e alkyl-O-Ci-6 alkyl-, or -C1-6 alkyl-NRa-Ci-6 alkyl unsubstituted, wherein said -C1-10 alkylsubstituted group is substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (C1-6 alkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino-, halo(Ci-s alkyl), halo (Ci-4 alkoxy)-, -C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -C1-4 alkoxy-(Ci-4 alkoxy)-, -NHCO(Ci-4 alkyl), phenyl optionally substituted, optionally substituted 5-6-membered heterocycloalkyl, and optionally substituted 56-membered heteroaryl, wherein said optionally substituted phenyl, 5-6-membered heterocycloalkyl, or 5-6-membered heteroaryl is optionally substituted with 1-4 substituents, each one independently selected from halogen, hydroxyl, amino, (Ci-salkyl)amino-, (C1-6 alkyl)(Ci6 alkyl)amino-, halo(Ci-6 alkyl), halo(Ci-4 alkoxy)-, -C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -C1-10 alkyl- group or is a -C1-10 alkyl-, -C2-io alkenyl- group. , -C2-io alkynyl-, -C1-6 alkyl-O-Ci-6 alkyl-, or -C1-6 alkyl-NRa-Ci-6 alkyl unsubstituted, wherein said -C1-10 alkylsubstituted group is substituted with 1-4 substituents, each independently selected from I CQb7n / 77n7 / 3 / YIAI halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (Ci-6alkyl)amino-, (Ci-6alkyl)( Ci-6alkyl)amino, halo(Ci-6alkyl), halo(Ci-4alkoxy)-, -C1-4 alkoxy-, hydroxy-(C2-4alkoxy¡)-, -Ci-4alkoxy-(Ci-4 alkoxy)- , -NHCO(Ci4 alkyl), optionally substituted phenyl, optionally substituted 5-6-membered heterocycloalkyl, and optionally substituted 5-6-membered heteroaryl, wherein said optionally substituted phenyl, 5-6-membered heterocycloalkyl, or 5-membered heteroaryl 6 members is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -OPÍOXR'R^, amino, (Cy alkyl)amino-, (Cy-6alkyl) (Ci-6alkyl)amino-, halo(Ci-e alkyl), halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy¡-(C2-4 alkoxy)-, and C1-4 alkoxy- (Ci-4 alkoxy)-. In some embodiments, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -C1-10 alkyl- group or is a -C1-10 alkyl-, -C2-10 alkenyl- group. , -C2-10 alkynyl-, -C1-6 alkyl-O-Ci-6 alkyl-, or -C1-6 alkyl-NRa-Ci-6 alkyl unsubstituted, wherein said -C1-10 alkylsubstituted group is substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, halo(Ci-4 alkyl), halo (Ci-4 alkoxy)-, and C1-4 alkoxy-. In some embodiments, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -C1-10alkyl- group or is a -C1-10alkyl-, -C2-10alkenyl- group, -C2-10 alkynyl-, -C1-6 alkyl-O-Ci-e alkyl-, or -C1-6 alkyl-NRa-Ci-6 alkyl- unsubstituted, wherein said -C1-10 alkyl- group is substituted substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (C1-4 alkyl)amino, (C1 -4 alkyl)(Ci-4 alkyl)amino-, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, and C1-4 alkoxy-. In some embodiments, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -C1-8 alkyl- group or is a -Ci-a alkyl-, -C2-8alkenyl- group, -C2-salkynyl-, -C1-4 alkylO-C1-4 alkyl-, or -C1-4 alkyl-NRa-Ci-4 alkyl- unsubstituted, wherein said substituted -C1-8 alkyl- group is substituted with 1 -4 substituents, each independently selected from halogen, hydroxyl, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci 4 alkyl)amino-, halo(Ci-4 alkyl), halo(Ci- 4 alkoxy)-, and C1-4 alkoxy-. In some embodiments, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -C1-8alkyl- group or is a -C1-8alkyl-, -C2-s alkenyl-, -group. C2-8 alkynyl-, -C1-4alkylO-C1-4 alkyl-, or -C1-4 alkyl-NRa-Ci-4 alkyl- unsubstituted, wherein said substituted -C1-8 alkyl- group is substituted with 1- 4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (C1-4 alkyl)amino, (C1-4 alkyl) (Ci-4 alkyl)amino-, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, and C1-4 alkoxy-. In some embodiments, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -C1-6 alkyl- group or is a -C1-6 alkyl-, -C2-6 alkenyl- group. , -C2-6alkynyl-, -Ci-2 alkylO-Ci-2 alkyl-, or -C1-2 alkyl-NRa-Ci-2 alkyl unsubstituted, wherein said substituted -Ci-s alkyl- group is substituted with 1-2 substituents, each independently selected from halogen, hydroxyl, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, halo(Ci-4 alkyl), halo( Ci-4 alkoxy)-, and C1-4 alkoxy-. In some embodiments, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -Ci-βalkyl- group or is a -Ci-β alkyl-, -C2-6 alkenyl- group, -Cz-βalkynyl-, -C1-2alkyl LCQfrzn / zznz / q / YiAi O-Ci-2 alkyl-, or -C1-2 alkyl-NRa-Ci-2 alkyl- unsubstituted, wherein said substituted -C1-6 alkyl- group is substituted with 1-2 substituents, each independently selected from halogen , hydroxyl, -O-P(O)(OH)2, amino, (Ci-4alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, halo(Ci-4 alkyl), halo(Ci- 4 alkoxy), and C1-4 alkoxy-. In some embodiments, r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -C2-4 alkyl- group or is a -C2-4 alkyl-, -C2-4alkenyl- group, -C2-4 alkynyl-, -C1-4alkylO-C1-4 alkyl-, or -C1-4 alkyl-NRa-Ci-4 alkyl- unsubstituted, wherein said substituted -C1-4 alkyl- group is substituted with 1 -2 substituents, each independently selected from halogen, hydroxyl, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, halo(Ci-4 alkyl), halo(Ci -4 alkoxy)-, and C1-4 alkoxy-. In some embodiments, r is 1, RB1 and RB2 are each independently -CH2-, and B is a -C2-4 alkyl-, -C2-4alkenyl-, -C2-4 alkynyl-, -C1 alkyl- group. O-Ci alkyl-, or -C1 alkyl-NRa-Ci substituted alkylon, wherein said substituted -C2-4 alkyl- group is substituted with 1-2 substituents, each independently selected from halogen, hydroxyl, -O-P(O) (OH)2, amino, (Ci-4alkyl)amino-, (Ci4 alkyl)(Ci-4 alkyl)amino-, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, and C1-4 alkoxy -. In some embodiments, r is 1, RB1 and RB2 are each independently -CH2-, and B is -CH=CH-, -CH2CH2-, -CH(OH)CH(OH)-, or -CH2N(CH3 )CH2-. In some embodiments, r is 1, B, taken together with RB1 and RB2, forms a group -CH2CH=CHCH2-, -CH2CH2CH2CH2-, CH2CH(OH)CH(OH)CH2-, or -CH2CH2N(CH3)CH2CH2- In some embodiments, r is 1, B, taken together with RB1 and RB2, forms a -CH2CH=CHCH2-, In some embodiments of the compounds of this invention, when s is 1, W1 and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D, taken together with RC1 and RC2, forms a linking group, where D is -halo(Ci-i2 alkyl)-, -C1-12 alkyl optionally substituted, -C2-12 alkenyl- optionally substituted, -C2-12 alkynyl- optionally substituted, -C1-6 alkyl -O-Ci-6 alkyl- optionally substituted, -Ci-β alkyl-NRa-Ci-6 alkyl- optionally substituted, -Cí e alkyl-(C3 6Cícloalkyl)-Ci-6 alkyl- optionally substituted, -Cí e -C1-6 alkyl-(5-6 membered heteroaryl)-Ci-6 optionally substituted alkyl, wherein the alkyl moiety of said -C1-12 alkyl- optionally substituted, -C2-12 alkenyl-optionally substituted, -C2-12 alkynyl- optionally substituted, -C1-6 alkyl-O-Ci-6 alkyl-optionally substituted , -C1-6alkyl-NRa-Ci-6 alkyl- optionally substituted, -Ci-6alkyl-(C3-6 cycloalkyl)C1-6 alkyl- optionally substituted, -C1-6 alkyl-phenyl-Ci-6 alkyl- optionally substituted , -C1-6 alkyl(4-6 membered heterocycloalkyl)-Ci-6 alkyl- optionally substituted, or -Ci-β alkyl-(56 membered heteroaryl-Ci-6 alkyl)- optionally substituted is optionally substituted with 1 or 2 substituents, each independently selected from halogen, halo(Ci-4 alkyl), -OH, -ORC, -NH2, -NRcRd, OCORC, -CO2H, -CO2Rc, -SORc, -SO2Rc-CONH2, -CONRcRd, - SO2NH2, -SO2NRcRd, -OCONH2, OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc, and the C3-6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said - C1-6 alkyl-(C3-6 cycloalkyl)-Ci-6 alkyl- optionally substituted, -C1-6 alkyl-phenyl-Ci-e alkyl- optionally substituted, Ci-e alkyl-(4-6 membered heterocycloalkyl)-Ci-6 alkyl- optionally substituted, or -Ci-β alkyl(5-6 membered heteroaryl)-Ci-6 alkyl- optionally substituted is optionally substituted with 1- 4 substituents, each independently selected from halogen, hydroxyl, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, C1-4 alkyl, halo(Ci-4 alkyl) , halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, and Ci-4alkoxy-(Ci-4 alkoxy)-. In some embodiments of the compounds of this invention, when s is 1, Wi and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D, taken together with RC1 and RC2, forms a linking group, where D is -halo(Ci-i2 alkyl)-, -C1-12 alkyl optionally substituted, -C2-12 alkenyl- optionally substituted, -C2-12 alkynyl- optionally substituted, -C1-6 alkyl -O-Ci-6 alkyl- optionally substituted, -C1-6 alkyl-NRa-Ci-6 alkyl- optionally substituted, -Ci-e alkyl-(C3-6 cycloalkyl)-Ci-6 alkyl- optionally substituted, -C1 -6 alkyl-phenyl-Ci-6 alkyloptionally substituted, -C1-6 alkyl-(4-6 membered heterocycloalkyl)-Ci-6 alkyl-optionally substituted, or -C1-6 alkyl-(5-6 membered heteroaryl) -Ci-6 alkyl- optionally substituted, wherein the alkyl moiety of said -C1-12 alkyl- optionally substituted, -C2-12 alkenyloptionally substituted, -C2-12 alkynyl- optionally substituted, -C1-6 alkyl-O-Ci -6alkyloptionally substituted, -Ci-6alkyl-NRa-Ci-6alkyl-optionally substituted, -C1-6alkyl-(Cs-6cycloalkyl)C1-6alkyl-optionally substituted, -C1-6alkyl-phenyl-Ci-6 alkyl- optionally substituted, -C1-6 alkyl(4-6-membered heterocycloalkyl)-Ci-6 alkyl- optionally substituted, or -C1-6 alkyl-(56-membered heteroaryl)-Ci-6 alkyl- optionally substituted is optionally substituted with 1 or 2 substituents, each independently selected from halogen, halo(Ci-4 alkyl), -OH, -O-P(O)(OH)2, -OPÍOXR'R'^.-OR0, -NH2, and the C3-6cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl moiety of said optionally substituted -Ci-e alkyl-(C3-s cycloalkyl)-Ci-6 alkyl-, -Ci- β alkyl-phenyl-Ci-e alkyl- optionally substituted, Cí e alkyl-(4-6 membered heterocycloalkyl)-Ci-6 alkyl- optionally substituted, or -C1-6 alkyl(5-6 membered heteroaryl)-Ci 6 alkyl-optionally substituted is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -OP(O)(R'R)2, amino, (Ci- 4alkyl)amino-, (Ci-4alkyl)(Ci-4alkyl)amino-, C1-4alkyl, halo(Ci-4 alkyl), halo(Ci4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy )-, -(C2-4 alkoxy)-O-P(O)(OH)2, -(C2-4 alkoxy¡)-0-P(0)(R'R)2, and C1-4 alkoxy-(Ci -4 alkoxy)-. In some embodiments of the compounds of this invention, s is 1, W1 and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D, taken together with RC1 and RC2, forms a liaison group of 4-8 members. In another embodiment, s is 1, W1 and Z2 are each independently C or N, and D, taken together with RC1 and RC2, forms a 4-6 member linking group. In yet another embodiment, s is 1 and D, taken together with RC1 and RC2, forms a 5-member link group. In some embodiments, when s is 1, W1 and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D is a substituted -C2-10 alkyl- group or is a LCQfrzn / zznz / q / viAi group -C2-10 alkyl-, -C2-10 alkenyl-, -C2-10 alkynyl-, -C1-4 alkyl-O-Ci-4 alkyl-, or -C1-4 alkyl- NRa-Ci-4 unsubstituted alkyl, wherein said substituted -C2-10alkyl- group is substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (C1-4 alkyl)amino-, (C1 -4 alkyl)(Ci-4 alkyl)amino-, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, and C1-4 alkoxy-. In some embodiments, s is 1, W1 and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D is a substituted -C2-10alkyl- group or is a C210 group. alkyl-, -C210 alkenyl-, -C2 10 alkynyl-, -C1-4 alkyl-O-Ci-4 alkyl-, or -C1-4 alkyl-NRa-Ci-4 alkyl unsubstituted, wherein said group - C2-10 substituted alkyl- is substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (C1- 4 alkyl)amino-, (Ci-4alkyl)(Ci-4alkyl)amino-, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, and C1-4 alkoxy-. In some embodiments, s is 1, W1 and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D is a substituted -C2-8alkyl- group or is a - group - C2a alkyl-, -C2-8 alkenyl-, -C2-8 alkynyl-, -C1-2 alkyl-O-Ci-2 alkyl-, or -C1-2 alkyl-NRa-Ci-2 alkyl- unsubstituted, in wherein said substituted -C2-8 alkyl- group is substituted with 1-2 substituents, each independently selected from halogen, hydroxyl, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl) amino-, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, and C1-4 alkoxy-. In some embodiments, s is 1, W1 and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D is a substituted -C2-8alkyl- group or is a - group - C28 alkyl-, -C2-8 alkenyl-, -C2-8 alkynyl-, -C12 alkyl-O-Ci-2 alkyl-, or -C1-2 alkyl-NRa-Ci-2 alkyl unsubstituted, wherein said -C2-8 alkyl-substituted group is substituted with 1-2 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, ( C1-4 alkyl)amino-, (Ci-4alkyl)(Ci-4alkyl)amino-, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, and C1-4 alkoxy-. In some embodiments, s is 1, W1 and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D is a substituted -C2-6alkyl- group or is a - group. C26 alkyl-, -C26 alkenyl-, -C26 alkynyl-, -C1-2 alkyl-O-Ci-2 alkyl-, or -C1-2 alkyl-NRa-Ci-2 alkyl unsubstituted, wherein said group - C2 6 alkyl-substituted is substituted with 1-2 substituents, each independently selected from halogen, hydroxyl, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, halo( Ci-4 alkyl), halo(Ci-4 alkoxy)-, and C1-4 alkoxy-. In some embodiments, s is 1, W1 and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D is a substituted -C2-6 alkyl- group or is a group -C26 alkyl-, -C2-6 alkenyl-, -C2-6 alkynyl-, C1-2 alkyl-O-Ci-2 alkyl-, or -C1-2 alkyl-NRa-Ci-2 alkyl- unsubstituted, in wherein said substituted -C2-6 alkyl- group is substituted with 1-2 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino , (C1-4 alkyl)amino-, (Ci-4alkyl)(Ci-4alkyl)amino-, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, and C1-4 alkoxy-. In some embodiments, s is 1, W1 and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D is a -C2-4 alkyl- group, -C2-4 alkenyl-, or -C2-4 alkynyl-. LCQfrzn / zznz / q / viAi In some embodiments, s is 1, Wi and Z2 are each independently, C or N, RC1 and RC2 are each independently -CH2-, and D is -CH2CH2CH2-, where D, taken together with RC1 and RC2, forms a group -CH2CH2CH2CH2CH2-. In some embodiments, R3 and R5 are, each independently, -CON(Rd)(R*), CH2N(Rd)(Rf), -N(Rd)(Rf), -N(Rd)CO(Rf), or -CH2N(Rd)CO(Rf). In some embodiments, one of R3 and R5 is -CON(Rd)(Rf), -CH2N(Rd)(Rf), -N(Rd)(Rf), N(Rd)CO(Rf) or -CH2N(Rd )CO(Rf), and the other of R3and R5is H, COOH or -CO2RC. In some embodiments, R3 and R5 are, each independently, -ΟΟΝ^χΡ'), or one of R3 and R5 is -CON(Rd)(Rf), and the other of R3 and R5 is H, COOH, or -CO2RC. In some embodiments, R3 and R5 are each independently -CON(Rd)(Rf), or one of R3 and R5 is -CON(Rd)(Rf), and the other of R3 and R5 is H or -CO2RC. In some embodiments, R3 and R5 are each independently CON(Rd)(Rf). In some embodiments, one of R3 and R5 is -CON(Rd)(Rf) and the other of R3 and R5 is H. In some embodiments, one of R3 and R5 is -CON(Rd)(Rf) and the other of R3 and R5 is -CO2RC. In some embodiments, one of R3 and R5 is -CON^XRj and the other of R3 and R5 is -CON(Rd)(Rf). In some embodiments, R3 and R5 are, each independently, -CH2N(Rd)(Rf) or one of R3 and R5 is -CH2N(Rd)(R1), and the other of R3 and R5 is H, COOH, or -CO2RC. In some embodiments, R3 and R5 are each independently -CH2N(Rd)(Rf) or one of R3 and R5 is -CH2N(Rd)(Rf), and the other of R3 and R5 is H or -CO2RC. In some embodiments, R3 and R5 are each independently CH2N(RdXRf). In some embodiments, one of R3 and R5 is -CH2N(Rd)(Rf) and the other of R3 and R5 is H. In some embodiments, one of R3 and R5 is -CH2N(Rd)(Rf) and the other of R3 and R5 is -CO2(RC). In some embodiments, one of R3y Rs is -CH2N(Rd)(R*) and the other of R3y R5 is -CONCR^ÍRj. In some embodiments, R3 and R5 are, each independently, -N(Rd)(Rf) or one of R3 and R5 is -N(Rd)(Rf), and the other of R3 and R5 is H, COOH, or -CO2(RC ). In some embodiments, R3 and R5 are, each independently, -N(Rd)(Rf) or one of R3 and R5 is -N(Rd)(Rf), and the other of R3 and R5 is H or -CO2RC. In some embodiments, R3 and R5 are, each independently, -N(Rd)(Rj. In some embodiments, one of R3 and R5 is -N(Rd)(Rf) and the other of R3 and R5 is H. In some embodiments, embodiment, one of R3y R5 is -NÍR^ÍRj and the other of R3y R5 is -CO2RC. In some embodiments, one of R3y R5 is -N(Rd)(Rf) and the other of R3y R5 is -CON(Rd)( RF). In some embodiments, R3 and R5 are, each independently, -N(Rd)CO(Rf) or one of R3 and R5 is -N(Rd)CO(Rf), and the other of R3 and R5 is H, COOH, -CO2RCo - ΟΟΝ^χκγ In some embodiments, R3 and R5 are, each independently, -N(Rd)CO(Rf) or one of R3 and R5 is -N(Rd)CO(Rf), and the other of R3 and R5 is H or -CO2RC . In some embodiments, R3 and R5 are each independently -NÍR^COÍRj. In some embodiments, one of R3y R5 is -NÍR^COÍRj and the other of R3y R5 is H. In some embodiments, one of R3y R5 is -N(Rd)CO(Rf) and the other of R3y R5 is -CO2Rc. In some embodiments, one of R3 and R5 is -N(Rd)CO(Rf) and the other of R3 and R5 is CON(RdXRf). In some embodiments, R3 and R5 are, each independently, -CH2N(Rd)CO(Rf) or one of R3 and R5 is -CH2N(Rd)CO(Rf), and the other of R3 and R5 is H, COOH, -CO2RCo - WITH(RdXR*). In some I CQb7n / 77n7 / 3 / YIAI embodiments, R3and R5are, each independently, -CH2N(Rd)CO(Rf) or one of R3and R5is CH2N(Rd)CO(Rf), and the other of R3and R5is H or -CO2Rc. In some embodiments, R3 and R5 are, each independently, -CH2N(Rd)CO(Rf). In some embodiments, one of R3 and R5 is CH2N(Rd)CO(Rf), and the other of R3 and R5 is H. In some embodiments, one of R3 and R5 is CH2N(Rd)CO(Rf), and the other of R3y R5is -CO2RC. In some embodiments, one of R3 and R5 is CH2N(Rd)CO(Rf) and the other of R3 and R5 is -CON(Rd)(Rf). In some embodiments, R3 and R5 are each -CONH2. In some embodiments, one of R3 and R5 is -CH2NH2, and the other of R3 and R5 is -CONH2. In some embodiments, one of R3 and R5 is -CONH2, and the other of R3 and R5 is -COOCH3. In some embodiments, one of R3 and R5 is -CH2N(CH3)2, and the other of R3 and R5 is -CONH2. In some embodiments, one of R3 and R5 is -CH2NHC(O)CH3, and the other of R3 and R5 is -CONH2. In some embodiments, one of R3 and R5 is -NHC(O)CH3, and the other of R3 and R5 is -CONH2. In some embodiments, one of R3 and R5 is -NH2, and the other of R3 and R5 is -CONH2. In some embodiments, R4 and R6 are each independently H, halogen, halo(Ci-4 alkyl), halo(Ci-e alkoxy)-, hydroxyl, -NH2, -NRCRC, -NRcRd, -CORC, -CO2RC , -N(Rd)CORc, N(Rd)SO2Rc, -N(Rs)SO2(Ci-2alkyl)-N(Rh)(Rf), -N(R9)CO(Ci-2alkyl)-N(Rh )(Rf), optionally substituted (C1-4 alkyl), optionally substituted (C1-6 alkyl)oxy¡-, optionally substituted (C1-6 alkyl)amino, or (C1-6 alkyl)(Ci-4 alkyl) optionally substituted amino-, wherein the (Ove alkyl) of said optionally substituted (Ci-b alkyl), (Ove alkyl)oxyoptionally substituted, (C1-5 alkyl)amino- optionally substituted and (C1-6 alkyl)(Ci- Optionally substituted 4alkyl)amino is optionally substituted with 1-4 substituents, each independently selected from the group -OH, -ORC, -NH2, -NRCRC, -NRcRd, -CO2H, -CO2RC, OCORC, -CO2Rd-SORC, - SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, NRdCORc, -NRdSORc, -NRdCO2Rc, -NRdSO2Rc, optionally substituted phenyl, optionally substituted 5-6 membered heterocycloalkyl, and 5-6 heteroaryl optionally substituted membered phenyl, wherein said optionally substituted phenyl, 5-6 membered heterocycloalkyl, or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (C1-4 alkyl )amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, C1-4 alkyl, halo(Ci-4 alkyl), hydroxy-(Ci-4 alkyl)-, halo(Ci-4 alkoxy)- , C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, C1-4 alkoxy-(Ci-4 alkoxy)-, -CORd, CON^XRf), and -CO2Rd. In some embodiments, R4 and R6 are each independently H, halogen, halo(Ci-4 alkyl), halo(Ci-6 alkoxy)-, hydroxyl, -O-P(O)(OH)2, -O-R(O )(R'R)2, -NH2, -NRCRC, -NRcRd, -CORC, -CO2Rc, -N(Rd)CORc, -N(Rd)SO2Rc, -N(Ra)SO2(Ci-2alkyl)-N (Rh)(R, -N(R9)CO(Ci-2 alkyl^-MÍR^R1), (Ci-e alkyl) optionally substituted, (C2-6 alkyl)oxy- optionally substituted, (C1-6 alkyl) optionally substituted amino, or optionally substituted (C1-6 alkyl)(Ci-4 alkyl)amino-, wherein the (Ci-s alkyl) of said optionally substituted (C1-6 alkyl), optionally substituted (C1-6 alkyl)oxy, -Ci-e alkyl)amino- optionally substituted and (Ove alkyl)(Ci-4 alkyl)amino-optionally substituted is optionally substituted with 1-4 substituents, each CQbzn / zznz / zi / YiAi independently selected from -OH, -O-P(O)(OH)2, -O-P(O)(R'R)2, -ORC, -NH2, -NRCRC, -NRcRd, -CO2H, -CO2Rc, OCORc, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, -NRdSO2Rc, optionally substituted phenyl, heterocycloalkyl -6-membered optionally substituted and optionally substituted 5-6-membered heteroaryl, wherein said optionally substituted phenyl, optionally substituted 5-6-membered heterocycloalkyl and optionally substituted 5-6-membered heteroaryl are optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (Ci-4alkyl)amino-, (Ci-4alkyl)(Ci-4alkyl)amino-, C1-4 alkyl, halo(Ci-4alkyl), hydroxy-(Ci-4alkyl )-, (C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-O-P(O)(R'R)2, halo(Ci-4 alkoxy)-, C1 -4alkoxy-, hydroxy-(C2-4 alkoxy)-, (C2-4 alkoxy)-O-P(O)(OH)2, -(C2.4 alkoxy)-O-P(O)(R'R)2, C1 -4 alkoxy-(Ci-4 alkoxy)-, -CORd, -CON(Rd)(Rf), and CO2Rd. In some embodiments, R4 and R6 are each H. In some embodiments, R4 and R6 are each independently halogen, halo(Ci-4 alkyl), halo(Ci-6 alkoxy)-, hydroxyl, -O-P(O)(OH)2, -O-P(O)( R'R)2, -ΝΗ2, -NRCRC, -NRcRd, -CORC, -CO2RC, -N(Rd)CORc, -N(Rd)SO2Rc, -N(R9)SO2(Ci-2alkyl)-N(Rh )(R, -N(R9)CO(Ci-2alkyl-NCR^ÍRf), (Ci-Balkyl) optionally substituted, (C2-6 alkyl)oxy- optionally substituted, (C1-6 alkyl)amino- optionally substituted, or (Οι-e alkyl)(Ci-4 alkyl)amino-optionally substituted, wherein the (Ci-β alkyl) of said optionally substituted (C1-6 alkyl), (C1-6 alkyl)oxyoptionally substituted, -Ci- e optionally substituted alkyl)amino and optionally substituted (C1-6 alkyl)(Ci-4 alkyl)amino is optionally substituted with 1-4 substituents, each independently selected from -OH, -O-P(O)(OH)2, - O-P(O)(R'R)2, -ORC, -NH2, -NRCRC, -NRcRd, -CO2H, -CO2Rc, OCORc, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, - SO2NRcRd, -OCONH2, OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, -NRdSO2Rc, optionally substituted phenyl, optionally substituted 5-6-membered heterocycloalkyl and optionally substituted 5-6-membered heteroaryl, wherein said optionally substituted phenyl, optionally substituted 5-6-membered heterocycloalkyl Optionally substituted 5-6 membered and optionally substituted 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (Ci-4alkyl)amino-, (Ci-4alkyl) (Ci-4alkyl)amino-, C1-4alkyl, halo(Ci-4alkyl), hydroxy-(Ci-4alkyl)-, (C1-4alkyl)-O-P(O)(OH)2, -( C1-4 alkyl)-O-P(O)(R'R)2, halo(Ci-4 alkoxy)-, C1-4alkoxy-, hydroxy-(C2-4 alkoxy)-, (C2-4 alkoxy)- O-P(O)(OH)2, -(C2.4 alkoxy)-O-P(O)(R'R)2, C1-4 alkoxy-(Ci-4 alkoxy)-, -CORd, -CON^XRf), and CO2Rd. In some embodiments, R4 is H. In some embodiments, R4 is halogen, halo(C1-4 alkyl), halo(Ci-s alkoxy)-, hydroxyl, -O-P(O)(OH)2i -O-P(O)(R'R)2, - ΝΗ2, -NRcRc, -NRcRd, -CORC, -CO2RC, -N(Rd)CORc, -N(Rd)SO2Rc, N(R9)SO2(Ci-2alkyl)-N(RhXR, -N(R9)CO( Ci-2alkyl)-N(Rh)(Rf), (C1-6 alkyl) optionally substituted, (C2-6 alkyl)ox¡- optionally substituted, (Ci-β alkyl)amino- optionally substituted, or (C1 -6 alkyl)(Ci-4 alkyl)amino- optionally substituted, LCQfrzn / zznz / q / viAi wherein the (Ci-s alkyl) of said (0-6 alkyl) optionally substituted, (C1-6 alkyl)oxyoptionally substituted, -Ove alkyl)amino- optionally substituted and (Ove alkyl)( Optionally substituted Ci-4 alkyl)amino is optionally substituted with 1-4 substituents, each independently selected from -OH, -O-P(O)(OH)2, -O-P(O)(R'R)2, -ORC, - NH2, -NRCRC, -NRcRd, -CO2H, -CO2RG, OCORc, -CO2Rc, -SORg, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc , -NRdSO2Rc, optionally substituted phenyl, optionally substituted 5-6-membered heterocycloalkyl and optionally substituted 5-6-membered heteroaryl, wherein said optionally substituted phenyl, optionally substituted 5-6-membered heterocycloalkyl and optionally substituted 5-6-membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (Ci-4alkyl)amino-, (Ci-4alkyl)(Cy-4alkyl)amino-, C1-4alkyl, halo (Ci-4alkyl), hydroxy-(Ci-4alkyl)-, (C1-4alkyl)-O-P(O)(OH)2, -(C1-4alkyl)-O-P(O)(RlR)2, halo(Ci-4 alkoxy)-, C1-4alkoxy-, hydroxy-(C2-4 alkoxy)-, (C2-4 alkoxy)-O-P(O)(OH)2, -(C2-4 alkoxy)-O-P( O)(R'R)2, C1-4 alkoxy-(Ci-4 alkoxy)-, -CORd, -CON(Rd)(Rf), and CO2Rd. In some embodiments, R6 is H. In some embodiments, R6 is halogen, halo(C1-4 alkyl), halo(Ci-6 alkoxy)-, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, -NH2, -NRcRc, -NRcRd, -CORC, -CO2RC, -N(Rd)CORc, -N(Rd)SO2Rc, N(R9)SO2(Ci-2alkyl)-N(Rh)(R, -N( R9)CO(Ci-2alkyl)-N(Rh)(Rf), optionally substituted (C1-6 alkyl), optionally substituted (C2-6 alkyl)oxy, optionally substituted (Ci^ alkyl)amino, or (C1 -6 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the (C1-6 alkyl) of said (C1-6 alkyl) optionally substituted, (C1-6 alkyl)oxyoptionally substituted, -Ci-e alkyl) optionally substituted amino- and optionally substituted (Ove alkyl)(Ci-4 alkyl)amino is optionally substituted with 1-4 substituents, each independently selected from -OH, -O-P(O)(OH)2, -O-P(O)( RIR)2, -ORC, -NH2, -NRCRC, -NRcRd, -CO2H, -CO2Rc, OCORc, -CO2Rc, -SORc, -SO2Rc, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, -NRdSO2Rc, optionally substituted phenyl, optionally substituted 5-6 membered heterocycloalkyl and optionally substituted 5-6 membered heteroaryl, wherein said optionally substituted phenyl, optionally substituted 5-6 membered heterocycloalkyl and optionally substituted 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxy, amino, (Ci-4alkyl)amino-, (Ci-4alkyl)(Ci-4alkyl)am¡ non-, C1-4alkyl, halo(Ci-4alkyl), hydroxy-(Ci-4alkyl)-, (C1-4alkyl)-O-P(O)(OH)2, -(C1-4alkyl)-O-P (O)(RlR)2, halo(Ci-4 alkoxy)-, C1-4alkoxy-, hydroxy-(C2-4 alkoxy)-, (C2-4 alkoxy)-O-P(O)(OH)2, -( C2-4 alkoxy)-O-P(O)(R'R)2, C1-4 alkoxy-(Ci-4 alkoxy)-, -CORd, -CON^XR'), and CO2Rd. In some embodiments, R14 is absent, or is H, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC , -CONRcRd, -SO2NRGRd, and -OCONRcRd. In some embodiments, R14 is absent. CQbzn / zznz / zi / YiAi In some embodiments, R14 is H, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R14 is H. In some embodiments, R14 is halogen or Ci-4 optionally substituted alkyl, wherein said Ci-4 optionally substituted alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R14 is halogen. In some embodiments, R14 is Ci-4 optionally substituted alkyl, wherein said optionally substituted C14 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R14 is optionally substituted Ci-4alkyl, wherein said optionally substituted C14alkyl is optionally substituted with a halogen. In some embodiments, R14 is Ci-4 optionally substituted alkyl, wherein said optionally substituted C14 alkyl is optionally substituted with a substituent selected from ORC, -NRcRd, -CO2Rc, -CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R14 is Ci-4 substituted alkyl, wherein said Ci-4 substituted alkyl is substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R14 is Ci-4alkyl. In some embodiments, R14 is methyl or ethyl. In some embodiments, R14 is methyl. In some embodiments, R14 is ethyl. In some embodiments, R14 is C1-4 substituted alkyl, wherein said C1-4 substituted alkyl is substituted with a halogen. In some embodiments, R14 is Ci-4 substituted alkyl, wherein said C1-4 substituted alkyl is substituted with a substituent selected from -ORC, -NRcRd, -CO2RC, -CONRcRd, SO2NRcRd, and -OCONRcRd. In some embodiments, R14 is -CH2COOH. In some embodiments, R16 is H or absent. In some embodiments, R16 is H. In some embodiments, R16 is absent. In some embodiments, R16 is H, halogen, or Ci-4alkyl. In some embodiments, R16 is halogen. In some embodiments, R16 is Ci-4alkyl. In some embodiments, R16 is methyl or ethyl. In some embodiments, R16 is methyl. In some embodiments, R16 is ethyl. In some embodiments, R15 and R17, each independently, are absent, or are H, cyclopropyl, halogen or optionally substituted Ci-4 alkyl, wherein said optionally substituted Ci-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, CO2Rc, -CONRcRd, -SO2NRcRd, and -OCONRcRd; o R15y Taken together with the atom or atoms through LCQfrzn / zznz / q / viAi of which are connected, form a ring of 5-6 members; o R16y Taken together with the atom or atoms through which they are connected, they form a 5-6 membered ring. In some embodiments, R15 and R17, each independently, are absent, or are H, cyclopropyl, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen. , -ORC, -NRcRd, CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; o R15and R19 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring. In some embodiments, R15 and R17 are, each independently, absent. In some embodiments, R15 and R17 are each independently H, cyclopropyl, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, - NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd; o R15and R19 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring. In some embodiments, R15 and R17 are, each independently, H. In some embodiments, R15 and R17 are each independently halo(Ci-4 alkyl). In some embodiments, R15 and R17 are each independently cyclopropyl, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd; o R15and R19 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring. In some embodiments, R15 and R17 are each independently cyclopropyl, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd; In some embodiments, R15 and R1S, taken together with the atom or atoms through which they are connected, form a 5-6 membered ring. In some embodiments, R16 and R17 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring. In some embodiments, R15 and R17, each independently, are absent, or are H, cyclopropyl, or C1-4alkyl. In some embodiments, R15 and R17 are each methyl. In some embodiments, R15 is absent, or is H, cyclopropyl, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R15 is absent. In some embodiments, R15 is H, cyclopropyl, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2R0, - CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R15 is H. In some embodiments, R15 is halo(Ci-4 alkyl). In some embodiments, R15 is cyclopropyl, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R15 is absent, or is H, cyclopropyl, or C1-4alkyl. In some embodiments, R15 is cyclopropyl or C1-4alkyl. In some embodiments, R15 is absent, or is H, cyclopropyl, or C1-4alkyl. In some embodiments, R15 is cyclopropyl. In some embodiments, R15 is absent, or is H, cyclopropyl, or C1-4alkyl. In some embodiments, R15 is C1-4 alkyl. In some embodiments, R15 is each methyl. In some embodiments, R17 is absent, or is H, cyclopropyl, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R17 is absent. In some embodiments, R17 is H, cyclopropyl, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, - CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R17 is H. In some embodiments, R17 is halo(Ci-4 alkyl). In some embodiments, R17 is cyclopropyl, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C14 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd , and -OCONRcRd. In some embodiments, R17 is absent, or is H, cyclopropyl, or C1-4alkyl. In some embodiments, R17 is cyclopropyl or C1-4alkyl. In some embodiments, R17 is absent, or is H, cyclopropyl, or C1-4alkyl. In some embodiments, R17 is cyclopropyl. In some embodiments, R17 is absent, or is H, cyclopropyl, or C1-4alkyl. In some embodiments, R17 is C1-4 alkyl. In some embodiments, R17 is each methyl. In some embodiments, R18 and R19, each independently, are absent, or are optionally substituted H, halogen, or Cu alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd; or R17 and R18 taken together with the atom(s) through which they are connected, form a 5-6 membered ring. LCQfrzn / zznz / q / viAi In some embodiments, R18 and R19 are each independently absent. In some embodiments, R18 and R19 are each independently H, halogen, or optionally substituted Ci4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -OR°, -NRcRd, - CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; or R17 and R18 taken together with the atom(s) through which they are connected, form a 5-6 membered ring. In some embodiments, R18 and R19 are each independently H. In some embodiments, R18 and R19 are each independently halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC , -CONRcRd, -SO2NRcRd, and -OCONRcRd; or R17 and R18 taken together with the atom(s) through which they are connected, form a 5-6 membered ring. In some embodiments, R18 and R19 are each independently halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC , -CONRcRd, -SO2NRcRd, -CH2-CO2Rc, and -OCONRcRd. In some embodiments, R17 and R18 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring. In some embodiments, R18 is absent, or is H, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC , -CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R18 is absent. In some embodiments, R18 is H, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRGRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R18 is H. In some embodiments, R18 is halo(Ci-4 alkyl). In some embodiments, R18 is halogen or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRGRd, -CO2RC, -CONRGRd, and -SO2NRGRd . In some embodiments, R18 is halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORG, -NRGRd, -CO2RG, -CONRGRd, -SO2NRcRd , and -OCONRGRd. In some embodiments, R19 is absent, or is H, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORG, -NRGRd, -CO2RG , -CONRGRd, -SO2NRGRd, and -OCONRGRd. In some embodiments, R19 is absent. LCQfrzn / zznz / q / viAi In some embodiments, R19 is H, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R19 is H. In some embodiments, R19 is halo(Ci-4 alkyl). In some embodiments, R19 is halogen or optionally substituted C1-4 alkyl, wherein said optionally substituted Ci4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, and -SO2NRcRd. In some embodiments, R19 is halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRGRd, -CO2RC, -CONRGRd, -SO2NRGRd , and -OCONRGRd. In some embodiments, R15, R17, R18, or R19 are each independently absent, or are H, Ci-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRGRd, -SO2NRcRd, and -OCONRGRd. In some embodiments, R15, R17, R18, or R19, each independently, are absent, or are H, or C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen. In some embodiments, R15, R17, R18, or R19 are each independently -ORG, NRGRd, -CO2Rg, -CONRGRd, -SO2NRGRd, and -OCONRcRd. In some embodiments, R15 is absent, or is H, or C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORG, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R15 is absent, or is H, or C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen. In some embodiments, R15 is -ORG, -NRGRd, -CO2RG, -CONRGRd, -SO2NRGRd, and OCONRGRd. In some embodiments, R17 is absent, or is H, or C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORG, -NRGRd, -CO2RG, CONRGRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R17 is absent, or is H, or C1-4 alkyl, wherein the C1-4 alkyl is optionally substituted with a substituent selected from halogen. In some embodiments, R17 is -ORG, -NRGRd, -CO2RG, -CONRGRd, -SO2NRGRd, and OCONRGRd. In some embodiments, R18 is absent, or is H, or C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORG, -NRGRd, -CO2RG, CONRGRd, -SO2NRGRd, and -OCONRcRd. In some embodiments, R18 is absent, or is H, or C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen. LCQfrzn / zznz / q / viAi In some embodiments, R18 is -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and OCONRcRd. In some embodiments, R19 is absent, or is H, or C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R19 is absent, or is H, or C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen. In some embodiments, R19 is -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and OCONRcRd. In some embodiments, when Zi, Yi and Y2 are, each independently, C or N, R14, R18 and R19 each independently, are absent, or are C1-4 optionally substituted alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R14, R15, R16, R17, R18, and R19, each independently, are absent, or are H or C1-4 alkyl. In some embodiments, R14, R15, R16, R17, R18 and R19 are each independently C1-4 alkyl. In some embodiments, R14, R15, R16, R17, R18, and R19 are each independently C1-3alkyl (i.e., methyl or ethyl). In some embodiments, R14 is ethyl. In some embodiments, R14 is absent, or is C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, R14 is absent, or is C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen. In some embodiments, R14 is absent, or is Ci 4 alkyl, where Ci 4 alkyl is optionally substituted with a substituent selected from -ORC, -NRcRd, -CO2RC, -CONRcRd, SO2NRcRd, and -OCONRcRd. In some embodiments, R14 is absent, or is C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from -ORC and -NRcRd. In some embodiments, R14 is absent, or is C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from -CO2RC, -CONRGRd, -SO2NRcRd, and OCONRcRd. In some embodiments, R14 is absent, or is C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from -CO2H. In some embodiments, R14 is absent, or is C1-4 alkyl, or -CH2-CO2H. In some embodiments, RC2 is absent, or is C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd. LCQfrzn / zznz / q / viAi In some embodiments, RC2 is absent, or is C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen. In some embodiments, RC2 is absent, or is C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from -ORC, -NRcRd, -CO2RC, -CONRcRd, SO2NRGRd, and -OCONRcRd. In some embodiments, RC2 is absent, or is C1-4 alkyl, wherein C14 alkyl is optionally substituted with a substituent selected from -ORC and -NRcRd. In some embodiments, RC2 is absent, or is C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from -CO2RC, -CONRcRd, -SO2NRcRd, and OCONRcRd. In some embodiments, RC2 is absent, or is C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from -CO2H. In some embodiments, RC2 is absent, or is C1-4 alkyl, or -CH2-CO2H. In some embodiments, R19 is methyl. In some embodiments, R16 is ethyl. In some embodiments, R18 is methyl. In some embodiments, Raes H, -Rc, -CORG, -CO2H, -CO2RG, -SORG, -SO2RG, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, or -CH2CO2RG. In some embodiments, Raes H, C1-4 alkyl, -CO(Ci-4 alkyl), -CO(Ci-4 alkyl)-OH, CO(Ci-4 alkyl)-O-(Ci-4 alkyl) , -CO(Ci-4 alkyl)-NH2, -CO(Ci-4 alkyl)-NH(Ci-4 alkyl), or -CO(Ci-4 alkyl)N(Ci-4alkyl)(Ci-4 alkyl) . In some embodiments, Raes H. In some embodiments, Ra is -RG, -CORG, -CO2H, -CO2RG, -SORG, -SO2RG, -CONH2, CONRGRd, -SO2NH2, -SO2NRGRd, or -CH2-CO2RC. In some embodiments, Raes -RG. In some embodiments, Raes -CORG. In some embodiments, Raes -CO2H. In some embodiments, Raes -CO2RG. In some embodiments, Raes -SORG. In some embodiments, Raes -SO2RG. In some embodiments, Raes -CONH2. In some embodiments, Raes -CONRGRd. In some embodiments, Ra is -SO2NH2. In some embodiments, Raes -SO2NRGRd. In some embodiments, Raes -CH2-CO2RG. In some embodiments, Ra is CH2-CO2H. In some embodiments, each Rbes independently C1-4 alkyl, halo(Ci-4 alkyl), (C1-4 alkyl)-OH, -(C1-4 alkyl)-O-P(O)(OH)2, -( C1-4 alkyl)-O-P(O)(R'R)2, -(C1-4 alkyl)-O-(Ci-4 alkyl), -(C1-4 alkyl)-N(Re)(Rf), -(C1-4 alkyl)-O-CO(Ci-4 alkyl), or -(C1-4 alkyl)-CO-O-(Ci-4 alkyl). In some embodiments, each Rbes independently C1-4 alkyl. In some embodiments, each Rbes independently halo(Ci-4 alkyl), -(C1-4 alkyl)OH, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkylO- O-PÍOJÍR'R1^, -(C1-4 alkyl)-O-(Ci-4 alkyl), -(C1-4 alkyl)N(Re)(R*), -(C1-4 alkyl)-O- CO(Ci-4 alkyl), or -(C1-4 alkyl)-CO-O-(Ci-4 alkyl). In some embodiments, each R is independently H, C1-4 alkyl, halo(Ci-4 alkyl), -(C1-4 alkyl)-OH, -(C1-4 alkyl)-O-P(O)(OH)2 , -(C1-4 alkyl)-O-P(O)(R'R)2, -(C1-4 alkyl)-O-(Ci-4 alkyl), -(C1-4 alkyl)-N(Re)( R*), -(C1-4 alkyl)-O-CO(Ci-4 alkyl), -(C1-4 alkyl)-CO-O-(Ci-4 alkyl), C3-6 cycloalkyl optionally substituted, phenyl optionally substituted, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, optionally substituted 9-10 membered heteroaryl, -C1-4 alkyl-Cs-e optionally substituted cycloalkyl, -C14 optionally substituted alkyl-phenyl, -C1-4 optionally substituted 4-6 membered alkylheterocycloalkyl, -optionally substituted -C1-4 5-6 membered alkylheteroaryl, or -optionally substituted -C1-4 9-10 membered alkylheteroaryl, wherein the remainder C3-6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl or 9-10 membered heteroaryl of said optionally substituted C3-6 cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, heteroaryl optionally substituted 5-6 membered, optionally substituted 9-10 membered heteroaryl, -C1-4 alkyl-C36 optionally substituted cycloalkyl, -C1-4 optionally substituted alkyl-phenyl, -C1-4 optionally substituted 4-6 membered alkylheterocycloalkyl , -C1-4 optionally substituted 5-6 membered alkylheteroaryl, or -optionally substituted -C1-4 9-10 membered alkylheteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, - O-P(O)(OH)2, -O-PfOXR'R)^ amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino, C1-4 alkyl, halo(Ci -4 alkyl), halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-OP(O)(OH)2, -(C2 -4alkoxy)-0-P(0)(R'R)2, C1-4 alkoxy-(Ci-4 alkoxy)-, -CORd, -CON(Rd)(Rf), and -CO2Rd. In some embodiments, each Rces independently H. In some embodiments, each R is independently C1-4 alkyl, halo(Ci-4 alkyl), (C1-4 alkyl)-OH, -(C1-4 alkyl)-O-P(O)(OH)2, -( C1-4 alkylD-O-PtOXR'R'X, -(Ci-4 alkyl)-O-(Ci-4 alkyl), -(Ci-4 alkyl)-N(Re)(Rf), -( C1-4 alkyl)-O-CO(Ci-4 alkyl), -(C1-4 alkyl)-CO-O-(Ci-4 alkyl), C3-6 optionally substituted cycloalkyl, optionally substituted phenyl, 4-heterocycloalkyl 6-membered optionally substituted, 5-6-membered heteroaryl optionally substituted, 9-10-membered heteroaryl optionally substituted, -C1-4alkyl-C3-6cycloalkyl optionally substituted, -Ci-4alkyl-phenyl optionally substituted, -C1-4alkyl -optionally substituted 4-6 membered heterocycloalkyl, optionally substituted -5-6 membered -C1-4 alkylheteroaryl, or optionally substituted -9-10 membered -Ci-4alkylheteroaryl, wherein the moiety C3-6 cycloalkyl, phenyl , 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl or 9-10 membered heteroaryl of said optionally substituted C3-6 cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally 5-6 membered heteroaryl substituted, optionally substituted 9-10 membered heteroaryl, optionally substituted -Ci-4aIquÍI-C36 cycloalkyl, -Ci-4optionally substituted alkylphenyl, -Ci-4optionally substituted 4-6 membered alkylheterocycloalkyl, -Ci-45-5 alkylheteroaryl -6-membered optionally substituted, or -Ci-4-4-alkyl-heteroaryl optionally substituted 9-10 membered is optionally substituted with 1-4 substituents, each independently selected from LCQfrzn / zznz / q / viAi halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (C1-4 alkyl)amino-, (C1-4 alkyl) (Ci-4 alkyl)amino, C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2- 4 alkoxy)-OP(O)(OH)2, -(C2-4alkoxy)-O-P(O)(R'R)2, Ci-4 alkoxy-(Ci-4 alkoxy)-, -CORd, -CON( Rd)(Rj, and -CO2Rd. In some embodiments, each R is independently H, hydroxyl, or C1-4 alkyl. In some embodiments, each Rdes independently H or C1-4 alkyl. In some embodiments, each Rdes independently H or hydroxyl. In some embodiments, each R is independently hydroxyl or C1-4 alkyl. In some embodiments, each Rdes independently H. In some embodiments, each Rdes independently C1-4 alkyl. In some embodiments, each Rdes independently hydroxyl. In some embodiments, each R® is independently H, (C1-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), -CO2(Ci-4 alkyl), -(C1 -4 alkyl)amino, -(C1-4 alkyl)-Ci-4 alkoxy, -CO(optionally substituted 5-6 membered heterocycloalkyl), -CO-(Ci-4 alkyl)-(5-membered heterocycloalkyl) -6-membered optionally substituted), -CO-(optionally substituted 5-6-membered heteroaryl), -CO-(Ci4 alkyl)-(optionally substituted 5-6-membered heteroaryl), wherein optionally 5-6-membered heterocycloalkyl substituted or optionally substituted 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, C1- 4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy) O-P(O)(OH)2, -(C2-4 alkoxy)-0-P(0)(R'R)2 , C1-4 alkoxy-(Ci-4 alkoxy)-, CORd, -CON(Rd)(Rf), and -CO2Rd. In some embodiments, each R® is independently H. In some embodiments, each R® is independently (C1-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), -CO2(Ci-4 alkyl), -(C1-4 alkyl). alkyl)amino, -(C1-4 alkyl)-Ci-4 alkoxy, -CO-(5-6 membered heterocycloalkyl optionally substituted), -CO-(Ci-4 alkyl)-(5-6 membered heterocycloalkyl optionally substituted ), -CO-(optionally substituted 5-6-membered heteroaryl), -CO-(Ci-4 alkyl)(optionally substituted 5-6-membered heteroaryl), wherein optionally substituted 5-6-membered heterocycloalkyl or 5-6 members optionally substituted is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (C1 -4 alkyl)amino-, (C1-4 alkyl)(Ci-4 alkyl)amino-, C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy) O-P(O)(OH)2, -(C2-4 3ΐοοχί)-0-Ρ(0)(Ρ'Ρ)2, Ci-4 alkoxy-(Ci-4 alkoxy)-, CORd, -CON^XRj, and -CO2Rd. In some embodiments, each Rfes independently H, hydroxyl, or (C1-4 alkyl). In some embodiments, each Rfes independently H or (C1-4 alkyl). In some embodiments, each Rfes independently H or hydroxy. In some embodiments, each Rfes independently hydroxy or (C1-4 alkyl). In some embodiments, each Rfes independently H. In some embodiments, each Rfes independently (C1-4 alkyl). In some embodiments, each Rfes independently hydroxy. I CQb7n / 77n7 / 3 / YIAI In some embodiments, each of R1 and R are independently (0-6 alkyl)ox¡-. In some embodiments, each R1 is independently (Ci-e alkyl)oxy-, In some embodiments, each R is independently (C1-6 alkyl)oxy-. In some embodiments, Xs is N. In some embodiments, In some embodiments, In some embodiments, In some embodiments, In some embodiments, In some embodiments, In some embodiments, Xs is N. In some embodiments, Xs is CRA1, where RA1 is selected from H, halogen, hydroxy, -OCH2CH2CH2OH, -OCH2CH2CH2COOH, -OCH2CH2CH2NH2, -OCH3, and -Ν(Ρθ)(Ργ In some embodiments, Xs is CRA1, where RA1 is selected from halogen, hydroxy, -OCH2CH2CH2OH, -OCH2CH2CH2COOH, -OCH2CH2CH2NH2, -OCH3, and -ΝίΡθχΡΤ In some embodiments, Xs is CRA1, where RA1 is selected from hydroxyl, OCH2CH2CH2OH, -OCH2CH2CH2COOH, -OCH2CH2CH2NH2, -OCH3, and -N(Re)(Rf). In some embodiments, Xs is CRA1, where RA1 is selected from -OCH2CH2CH2OH, -OCH2CH2CH2COOH, -OCH2CH2CH2NH2, -OCH3, and -N(Re)(Rf). In some embodiments, Xs is CRA1, where RA1 is selected from H, halogen, hydroxyl, -OCH2CH2CH2OH, -OCH2CH2CH2COOH, -OCH2CH2CH2NH2, -OCH3, and -NH2. In some embodiments, Xs is CRA1, where RA1 is selected from halogen, hydroxy, -OCH2CH2CH2OH, -OCH2CH2CH2COOH, -OCH2CH2CH2NH2, -OCH3, and -NH2. In some embodiments, Xe is CRA1, where RA1 is selected from hydroxyl, OCH2CH2CH2OH, -OCH2CH2CH2COOH, -OCH2CH2CH2NH2, -OCH3, and -NH2. In some embodiments, In some embodiments, Xs is N and Xe is N. In some embodiments, X5 is CRA2 and Xe is CRA1. In some embodiments, X5 is CRA2 and Xe is N. In some embodiments, X5 is N and Xe is CRA1. In some embodiments, X5 is CRA2 and Xe is CRA1, where RAI is -OCH3 and RA2 is OCH2CH2CH2OH. LCQfrzn / zznz / q / viAi In some embodiments, Χε is CRA2 and Χε is CRA1, where RA1 is H and RA2 is OCH2CH2CH2OH. In some embodiments, X5 is CRA2 and Χε is CRA1, where RA1 is -OH and RA2 is OCH2CH2CH2OH. In some embodiments, Xs is CRA2 and Xe is CRA1, where RA1 is -OCH3 and RA2 is OCH2CH2CH2COOH. In some embodiments, Xs is CRA2 and Χε is CRA1, where RA1 is -OH and RA2 is OCH2CH2CH2COOH. In some embodiments, Xs is CRA2 and Xs is CRA1, where RA1 is -OCH3 and RA2 is OCH2CH2CH2NH2. In some embodiments, Xs is CRA2 and Xs is CRA1, where RA1 is -OH and RA2 is OCH2CH2CH2NH2. In some embodiments, Xs is N and Xs is CRA1, where RA1 is -OCH2CH2CH2OH. In some embodiments, Xs is N and Xs is CRA1, where RA1 is -OCH2CH2CH2COOH. In some embodiments, Xs is N and Xs is CRA1, where RA1 is -OCH2CH2CH2NH2. In some embodiments, Χε is N and Xs is CRA1, where RA1 is halogen. In some embodiments, Xs is N and Xs is CRA1, where RA1 is -OCH3. In some embodiments, Xs is N and Xs is CRA1, where RA1 is -OH. In some embodiments, Xs is CRA2 and In some embodiments, RA1 and RA2 are independently H, halogen, hydroxyl, OCH2CH2CH2OH, -OCH2CH2CH2COOH, -OCH2CH2CH2NH2, -OCH3, or -N^XRf). In some embodiments, X3 and X4 are each independently S or NRf, where Rfes H. In some embodiments, X3 is S and X4 is NRf, where Rfes H. In some embodiments, Xg is N or CR4. In some embodiments, Xg is N. In some embodiments, X9 is CR4. In some embodiments, X9 is CH. In some embodiments, the invention is directed to a compound of Formula (Ij, Formula (lAj, Formula (llj, Formula (lllj, Formula (IVj, or Formula (Vj where: the total of r and s is 1 or 2; X3 and X4 are each independently S or NRf; Xs is N or CRA2; X6es N or CRA1; Xg is N or CH; rai and RA2 are independently selected from H, halogen, hydroxyl, -OCH2CH2CH2OH, OCH2CH2CH2COOH, -OCH2CH2CH2NH2, -OCH3 and -NReRf. r is 0 and RB1 and RB2 are each H; or r is 1, RB1 and RB2 are, each independently, -CH2-, and B is -CH=CH-, -CH2CH2-, CH(OH)CH(OH)-, or -CH2N(CH3)CH2-; s is 0, Y1, Y2, Z1 and Z2 are each independently O or S; I CQb7n / 77n7 / 3 / YIAI s is 0, Wi is C, RC1 is methyl; s is 0, Z2 is C, RC2 is ethyl; s is 0, W1 is N, RC1 is absent; s is 0, Z2 is N, RC2 is absent or ethyl; s is 1, W1 and Z2 are each independently C or N, RC1 and RC2 are each independently -CH2-, and D is -CH2CH2CH2-; R3 and R5 are, each independently, -CONH2, -CH2NH2, -NH2, -CH2N(CH3)2, CH2NHC(O)CH3or -NHC(O)CH3; R4 and R6 are, each, H; R14 is absent, or is methyl or ethyl; R15 is absent, or is H or methyl; R16 is absent, or is H, methyl or ethyl; and R17 is absent, or is methyl, or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof. In some embodiments, the compound is of Formula (1-B): LCQfrzn / zznz / q / viAi R14 (l-B') or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Υι, Y2, Z1, and Z2 are each independently O, S, C, or N; Χι, X2, W1, and W2 are each independently C or N; X3, X4X5, Xe, X9, R3, R5, Rdy Rfson, each independently, as defined in Formula (lAj; Rces C1-4 alkyl; RB1 and RB2 are, each independently, -CH2-; B is -halo(Ci-5alkyl), -C1-5unsubstitutedalkyl, or -C2-5alkenyl-unsubstituted; ra2 and raíson cac|a un0independently, H, halogen, hydroxyl, amino, amino(Ci-4 alkyl)-, O-P(O)(OH)2, -O-P(O)(R'R)2, (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxyoptionally substituted, wherein the Ci-β alkyl of said (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxyoptionally substituted is optionally substituted with 1 -4 substituents, each independently selected from the group comprising hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, C1-4 alkoxy, -N(Re)(R* ), -CO2(R*), optionally substituted phenyl, and optionally substituted 5-6 membered heteroaryl; wherein said optionally substituted phenyl, or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-PO)(OH)2, -O-P(O)(R' R)2, amino, (Ci-6alkyl)amino-, (Os alkyl)(Ci-6alkyl)amino, halo(Ci-e alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl) -O-P(O)(OH)2, -(C1-4 alkylj-O-PIOXR'R^, halo(Ci-4 alkoxy)-, Ci-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, - (C2-4 alkoxy)-O-P(O)(OH)2, -(C2-4 alkoxy¡)-O-P(O)(R'R)2, -(C1-6 alkyl)-NH2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-; Rese selected from H, (C1-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), -(C1-4 alkyl)-NH2, (C1-4 alkyl)-Ci-4 alkoxy, and -CO2(Ci-4 alkyl); R4y Reson H; ru and rc2cac|a are independently absent, or are C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd; R16 and RC1, each independently, are absent, or are H or C1-4 alkyl; and R15, R17, R18, or R19 are each independently absent, or are H, C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2Rc, -CONRcRd, -SO2NRcRd, and -OCONRcRd; and each R1 and R are independently (Ci-6alkyl)ox¡-; provided that at least one of (i), (i), or (ii) applies: (i) when (a) Z1, Z2, Yt and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) Wz and X2 are each N, Z2 and Y2 are each C, then at least one of Xs and X4 is S; or Xg is N; or (i) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and , -SO2NRcRd, and -OCONRcRden where Rces H; or (ii) when (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Χε, and alkyl)oxy- substituted, (C1-6 alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the (C1-6 alkyl) of said (C1-6 alkyl) optionally substituted, (Ci-β alkyl)ox¡- substituted, (C1-6 alkyl)amino- optionally substituted, or (Ci-e alkyl)(Ci-4 alkyl)amino- optionally substituted is optionally substituted with 1- 4 substituents each independently selected from hydroxyl, LCQfrzn / zznz / q / viAi -Ο-Ρ(Ο)(ΟΗ)2ι-O-P(O)(R'R)2, -NfR^fR1), -CO^R1), -ΟΟΝ(Ρθ)(Ργ optionally substituted phenyl, and a heteroaryl group optionally substituted 5-6 membered, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, - O-P(O)(R'R)2, amino, (C1-6 alkyl)amino-, (Ci-e alkyl)(Ci-6 alkyl)amino-, -(Ci-s alkyl)-NHz, halo(Ci -s alkyl), hydroxy-(Ci-4 alkyl)-, -(Ci4 alkyl)-O-P(O)(OH)2, -(C14 alkylQ-O-PfOXR'R^, halo(Ci-4 alkoxy)- , C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(Cz4alkoxy)-O-P(O)(OH)2, -(C2 4alkoxy)-0-P(0)(RIR)2, -Cu alkyl-(Ci 4 alkoxy), and Cw alkoxy-(Ci-4 alkoxy)-. In some embodiments, the compound is of Formula (1-B'), where Xg is CR4. In some embodiments, the compound is of Formula (ll-Bj: LCQfrzn / zznz / q / viAi (ll-Bj or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Y2and Z2are, each independently, O, S, C, or N; X2 and Wz are, each independently, C or N; X3, X4, Xs, Xe, Xg, R3, R5, Rdy Rfson, each independently, as defined in Formula (lAj; Rces C1-4 alkyl; RB1and rb2 are cac|auno independently, -CH2-; B is -halo(Ci-5alkyl), unsubstituted -C1-5alkyl, or -unsubstituted -Cisalkenyl; ra2 and raíson cac|auno independently, H, halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, O-P(O)(OH)2, -O-P(O)(RiR)2, (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxy-optionally substituted, wherein the Ci-β alkyl of said (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxy-optionally substituted is optionally substituted with 1-4 substituents , each independently selected from the group comprising hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, C1-4 alkoxy, -N(Re)(Rj, -COz( Rj, optionally substituted phenyl, and optionally substituted 5-6 membered heteroaryl; wherein said optionally substituted phenyl, or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P (O)(OH)2, -O-P(O)(R'R)2, amino, (Ci-6alkyl)amino-, (Ci-6alkyl¡I)(Ci-6alkyl)amino, halo(Ci-6alkyl ), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkylj-O-PIOjíR'R1^, halo(Ci-4 alkoxy) -, Ci-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-O-P(O)(OH)2, -(C2-4 alkoxy)-O-P(O)(RlR) 2, -(C1-6 alkyl)-NH2, and C1-4 alkoxy-(Ci-4 alkoxy)-; R® is selected from H, (C1-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), -(C1-4 alkyl)NH2, -(C1-4 alkyl)-Ci 4 alkoxy, and -CO2(Ci-4 alkyl), R4 and R6 are H; RC2 is absent, or is C1-4 alkyl or -CH2COOH; R16 and RC1, each independently, are absent, or are H or C1-4 alkyl; and R17, R18, or R19, each independently, are absent, or are H, C1-4 alkyl or halo(Ci-4 alkyl); and each R1 and R are independently (Ci-6alkyl)oxy-, In some embodiments, the compound is of Formula (ll-B'), where Xg is CR4. In some embodiments, the compound is of Formula (1-B1), or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: ra2 and raíson caqauno independently, H, halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, O-P(O)(OH)2, -O-P(O)(RiR)2, (C1-6 alkyl) optionally substituted , or (C1-6 alkyl)oxy-optionally substituted, wherein the C1-6 alkyl of said (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxy-optionally substituted is optionally substituted with 1-4 substituents , each independently selected from the group comprising hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, C1-4 alkoxy, -N^XR1), -ΟΟ2(Ρ* ), optionally substituted phenyl, and optionally substituted 5-6 membered heteroaryl; wherein said optionally substituted phenyl, or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-PÍOjíR'R1^, amino, (Ci-6alkyl)amino-, (Ci-6alkyl)(Ci-6alkyl)amino, halo(Ci-6alkyl), hydroxy-(Ci-4alkyl)-, -(C1-4alkyl)-O-P( O)(OH)2, -(C1-4 alkylj-O-PÍOXR'R1^, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2- 4-alkoxy)-O-P(O)(OH)2, -(C2-4 alkoxy)-O-P(O)(RlR)2, -(C1-6 alkyl)-NH2, and C1-4 alkoxy-(Ci-4 alkoxy)-; provided that at least one of (i), (¡i), or (iii) applies: (i) when (a) Ζι, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or Xg is N; or (¡i) when (a) Ζι, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and SO2NRcRd, and -OCONRcRden where Rces H; either LCQfrzn / zznz / q / viAi (iii) when (a) Zi and Yi are each N, Wi and Xi are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) Wi and Xi are each N, Zi and Yi are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of substituted, (Ci-b alkyl)amino- optionally substituted, or (Ci-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the (Ct-e alkyl) of said (Ci-e alkyl) optionally substituted , (Cve alkyl)oxy-substituted, (Ci e alkyl)amino- optionally substituted, or (Ci-e alkyl)(Ci 4 alkyl)amino- optionally substituted is optionally substituted with 1-4 substituents each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, -N^XR1), -COXR1), -CONÍR^ÍRf), optionally substituted phenyl, and a 5-6 heteroaryl group optionally substituted member, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O) (R'R)2, amino, (Ci b alkyl)amino-, (Ci-b alkyl)(Ci-6 alkyl)amino-, -(Ci-b alkyl)-NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(Ci4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-O-P(O)(RlR)2, halo(Ci-4 alkoxy)- , C1-4alkoxy-, hydroxy-(C2-4alkoxy)-, -(C2. 4alkoxy)-O-P(O)(OH)2, -(C2-4alkoxy)-O-P(O)(RlR)2, -Ci-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci- 4 alkoxy)-. In some embodiments, the compound is of Formula (1-B') or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: RA2 and RA1 are, each independently, H, halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, (Ci-b alkyl) optionally substituted, or (Ci-b alkyl)oxy- optionally substituted, wherein the Ci- e alkyl of said (Ci-e alkyl) optionally substituted, or (Ci-e alkyl)oxyoptionally substituted is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxy, - N(R®)(R*), CO^Rf), optionally substituted phenyl, and optionally substituted 5-6 membered heteroaryl; wherein said optionally substituted phenyl, or 5-6 membered heteroaryl is optionally substituted with 14 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -OPÍOXR'R):?, amino, (O-e alkyl)amino-, (O-e alkyl)(Ci s alkyl)amino-, halo(Ci s alkyl), hydroxy-(Ci-4 alkyl)-, halo(Ci-4 alkoxy)-, C1-4 alkoxy- , hydroxy-(C2-4 alkoxy)-, and Cw alkoxy-(Ci-4 alkoxy)-; and Rese selected from H, (C1-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), and -CO2(Ci-4 alkyl); provided that at least one of (i), (i), or (iii) applies: (i) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or X9 is N; or (i) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and SO2NRcRd, and -OCONRcRden where Rces H; or (iii) when (a) Zi and Yi are each N, Wi and Xi are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X5, and Xb, and (C1-6 alkyl)oxy-substituted, (Cve alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the (C1-6 alkyl) of said ( C1-6 alkyl) optionally substituted, (C1-6 alkyl)oxy- substituted, (C1-6 alkyl)amino- optionally substituted, or (Cy alkyl)(Ci 4 alkyl)amino- optionally substituted is optionally substituted with 1-4 substituents each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R'j2, -N(Re)(Rj, -CO2(Rj, -CON(Re)(Rj , optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P (O)(OH)2, -O-P(O)(R'R)2, amino, (Cvb alkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino-, -(C1-6 alkyl )-NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C14 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl-O-PODXR'R^ , halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2. 4alkoxy)-O-P(O)(OH)2, -(C2-4alkoxy¡)-O-P(O)(RlR)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci -4 alkoxy)-. In some embodiments, the compound is of Formula (l-bj: LCQfrzn / zznz / q / viAi or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Υι, Y2, Z1, and Z2 are each independently O, S, C, or N; Χι, X2, W1, and W2 are each independently C or N; X3, X4, Xs, Xs, and X9 are, each independently, as defined in Formula (IAj;, B is -halo(Ci-5 alkyl), unsubstituted C1-5 alkyl, or unsubstituted -C2-5alkenyl; RA2 and raíSon, caqa unindependently, H, halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, O-P(O)(OH)2, -O-P(O)(R'Rh)2, (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxy¡- optionally substituted, wherein the Ove alkyl of said (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxy¡optionally substituted is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxy, -N(Re)(Rj, CC^RO, optionally substituted phenyl, and optionally substituted 56-membered heteroaryl; and wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -OP(O)(OH)2, -O-P(O)(R' R)2, amino, (Ci-s alkyl)amino-, (C1-6 alkyl)(Ci-6 alkyl)amino-, halo(Ci-e alkyl), hydroxy-(Ci-4 alkyl)-, -( C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-O-P(O)(R'R)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy- , hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-O-P(O)(OH)2, -(C2-4 alkoxy)-O-P(O)(RlRll)2, -(C1-6 alkyl)-NH2, -C1-4 alkyl(C1-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-; Rese selected from H, (C1-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), -(C1-4 alkyl)-NH2, (C1-4 alkyl)-Ci-4 alkoxy, and -CO2(Ci-4 alkyl), each Rfes independently H, hydroxyl, or (C1-4 alkyl); R4 and R6 are H; R14 and RC2 are each independently absent, or are C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd; R16 and RC1, each independently, are absent, or are H or C1-4 alkyl; R15, R17, R18, or R19 are each independently absent, or are H, C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2Rc, -CONRcRd, -SO2NRcRd, and -OCONRcRd; and each R1 and R are independently (C1-6 alkyl)oxy-, provided that at least one of (i), (i), or (iii) applies: (i) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or Xs is N; or (ii) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and SO2NRcRd, and -OCONRcRden where Rces H; or (iii) when (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Xb, and , optionally substituted (C1-6 alkyl)amino, or optionally substituted (C1-6 alkyl)(Ci-4 alkyl)amino, wherein the (C1-6 alkyl) of said optionally substituted (C1-6 alkyl), (C1-6 alkyl)oxy-substituted, (C1-6 alkyl)amino- optionally substituted, or (Ci-e alkyl)(Ci-4 alkyl)amino- optionally substituted is optionally substituted with 1-4 substituents each independently selected between hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, -N(Re)(R'), -CO^R1), -CON(Re)(Rf), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said phenyl optionally LCQfrzn / zznz / q / YiAi substituted or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R 'R)2, amino, (C1-6 alkyl)amino-, (Ci-s alkyl)(Ci-6 alkyl)amino-, -(C1-6 alkyl)-NH2, halo(Ci-6 alkyl), hydroxy -(Ci-4 alkyl)-, -(Ci4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-O-P(O)(RlR)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C24alkoxy)-O-P(O)(OH)2, -(C2-4 alkoxy)-O-P(O)(R'R)2, - C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-. In some embodiments, the compound is of Formula (l-bj or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein Xg is CR4. In some embodiments, the compound is of Formula (Il-bj: LCQfrzn / zznz / q / viAi or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Y2 and Z2 are each independently O, S, C or N; X2 and W2 are, each independently, C or N; X3, X4, Xs, Χβ, and X9 are, each independently, as defined herein; B is -halo(Ci-5alkyl), unsubstituted -C1-5alkyl, or unsubstituted -C2-5alkenyl; ra2 and raíson cac|auno independently, H, halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, O-P(O)(OH)2, -O-P(O)(R'Rh)2, (C1-6 optionally substituted alkyl), or optionally substituted (C1-6 alkyl)oxy-, wherein the C1-6 alkyl of said optionally substituted (C1-6 alkyl) or optionally substituted (C1-6 alkyl)oxy is optionally substituted with 1-4 substituents, each independently selected from the group consisting of hydroxyl, C1-4 alkoxy, -N(Re)(Rj, CÜ2(Rj, optionally substituted phenyl, and optionally substituted 56-membered heteroaryl; and wherein said phenyl optionally substituted or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -OP(O)(OH)z, -O-P(O)(R'RH)2, amino , (Ci-s alkyl)amino-, (Ci-b alkyl)(Ci-e alkyl)amino-, halo(Ci-e alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl) -O-P(O)(OH)2, -(C1-4 alkyl)-O-P(O)(RlR)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4alkoxy)- , -(C2-4alkoxy)-O-P(O)(OH)2, -(C2-4alkoxy)-O-P(O)(RlR)2, -(Ci-6alkyl)-NH2, and C1-4 alkoxy(C1- 4 alkoxy)-; Rese selected from H, (Ci-4alkyl), -CO(Ci-4alkyl), -OCO(Ci-4alkyl), -(Ci-4alkyl)-NH2, (C1-4alkyl)-Ci-4alkoxy, and -CO2(Ci-4alkyl), each Rfes independently H, hydroxyl, or (Ci-4alkyl); R4 and R6 are H; RC2 is absent, or is C1-4 alkyl or -CH2COOH; R1S and RC1, each independently, are absent, or are H or C1-4 alkyl; R17, R18, or R19, each independently, are absent, or are H, C1-4alkyl, or halo(Ci-4alkyl); and each R1 and R are independently (Ci-6alkyl)ox¡-. In some embodiments, the compound is of Formula (ll-b') or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein Xg is CR4. In some embodiments, the compound is of Formula (l-b') or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: ra2 and raíson cac|auno independently, H, halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, O-P(O)(OH)2, -O-P(O)(RiR)2, (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxy-optionally substituted, wherein the Ci-β alkyl of said (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxy-optionally substituted is optionally substituted with 1-4 substituents , each independently selected from the group comprising hydroxyl, C1-4 alkoxy, -N(Re)(Rf), CO2(Rf), optionally substituted phenyl, and optionally substituted 56-membered heteroaryl; and wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -OP(O)(OH)2, -O-P(O)(R' R)2, amino, (C1-6 alkyl)amino-, (C1-6 alkyl)(Ci-s alkyl)amino-, halo(Ci-e alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-O-P(O)(R'R)2, halo(Ci-4 alkoxy)- , C1-4 alkoxy-, hydroxy-(C2-4alkoxy)-, -(C2-4alkoxy)-O-P(O)(OH)2, -(C2-4alkoxy¡)-O-P(O)(R'R)2 , -(Ci-ealkyl)-NH2, and C1-4 alkoxy(C1-4 alkoxy)-; provided that at least one of (i), (i), or (iii) applies: (i) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or X9 is N; or (i) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and , -SO2NRcRd, and -OCONRcRden where Rces H; or (iii) when (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Xe, and C1-6 alkyl)oxy- substituted, (C1-6 alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, LCQfrzn / zznz / q / viAi wherein the (Ct-e alkyl) of said (C1-6 alkyl) optionally substituted, (Cí e alkyl)oxy- substituted, (C1-6 alkyl)amino- optionally substituted, or (Ove optionally substituted alkyl)(Ci-4 alkyl)amino- is optionally substituted with 1-4 substituents each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, - N / Rg / R*), -CO2(R*), -CON(Re)(Rf), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-membered heteroaryl -6 member is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(RIR)2, amino, (Cve alkyl)amino-, (O-s alkyl)(Ci-6 alkyl)amino-, -(Ci-e alkyl)-NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(Ci4 alkyl)-O-P(O )(OH)2, -(C1-4 alkyl)-O-P(O)(RlR)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -( C2. 4alkoxy)-O-P(O)(OH)2, -(C2-4alkoxy¡)-O-P(O)(RlR)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy- (Ci-4 alkoxy)-. In some embodiments, the compound of the invention has the Formula (l-bj or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: RA2y is a compound independently, H, halogen, hydroxyl, amino, optionally substituted amino(C1-6alkyl), wherein the Ci- e alkyl of said (0-6 alkyl) optionally substituted, or (0-6 alkyl)oxyoptionally substituted is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxy, -N( Re)(R*), CO2(Rf), optionally substituted phenyl, and optionally substituted 5-6 membered heteroaryl; and wherein said optionally substituted phenyl, or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (C1-6 alkyl)amino-, (C1-6 alkyl) (C1-6 alkyl)amino-, halo(C1-6 alkyl), hydroxy-(Ci-4 alkyl)-, halo(Ci-4 alkoxy)-, Ci-4 alkoxy-, hydroxy-(C2-4 alkoxy) -, and Cw alkoxy-(Ci-4 alkoxy)-; and Rees H, (Ci-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), or -CO2(Ci-4 alkyl); provided that at least one of (i), (i), or (ii) applies: (i) when (a) Zi, Z2, Yi and Y2 are each N, Wi, W2, Xi and X2 are each C; or (b) Wi, W2, Xi and X2 are each N, Zi, Z2, Yi and Y2 are each C; or (c) Zi and Yi are each N, Wi and Xi are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) Wi and Xi are each N, Zi and Yi are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or X9 is N; or (i) when (a) Ζι, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and SO2NRcRd, and -OCONRcRden where Rces H; or (iii) when (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Xe, and )oxy-substituted, (C1-6 alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, LCQfrzn / zznz / q / viAi wherein the (Cí e alkyl) of said optionally substituted (C1-6 alkyl), (Cí e alkyl)oxy- substituted, (C1-6 alkyl)amino- optionally substituted, or (Ci- e optionally substituted alkyl)(Ci-4 alkyl)amino is optionally substituted with 1-4 substituents each independently selected from hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, -N(Re)(Rj, -CO2(Rj, -CON(Re)(Rf), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl members is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-PfOXR'R^ amino, (Cve alkyl)amino-, (Ci-s alkyl ¡l)(Ci-e alkyl)amino-, -(Ci-e alkyl)-NH2, halo(Ci-e alkyl), hydroxy-(Ci-4 alkyl)-, -(Ci4 alkyl)-O-P(O) (OH)2, -(C1-4 alkyl)-O-P(O)(RlR)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2 4alkoxy)-O-P(O)(OH)2, -(C2-4alkoxy)-O-P(O)(RlR)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci -4 alkoxy)-. In some embodiments, the compound is of Formula (l-Bj, (ll-Bj, (l-bj, or (ll-bj, or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein RA2y RA1 are, each independently, H, halogen, hydroxyl, amino, amino(Ci-4 alkyl)-, (Ci-s alkyl) optionally substituted, or (0-6 alkyl)oxy- optionally substituted, and Ci-β alkyl of said optionally substituted (Ci-β alkyl), optionally substituted (Ci-β alkyl)oxy- is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, -OP(O)(OH)2 , -O-P(O)(R'R)2, -N(Re)(Rf), C1-4 alkoxy, phenyl, and optionally substituted 5-6 membered heteroaryl comprising at least one nitrogen or oxygen as a ring member , each R® is independently selected from H, C1-4 alkyl, -(C1-4 alkyl)NH2, and -(C1-4 alkyl)Ci-4 alkoxy, and each Rfes independently H, hydroxyl, or (C1-4 I rent). In some embodiments, the compound is of Formula (l-Bj, (ll-Bj, (l-bj, or (ll-bj, or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein RA2y RA1 are, each independently, H, halogen, hydroxyl, amino, amino(C1-6 alkyl)-, optionally substituted (C1-6 alkyl), or optionally substituted (C1-6 alkyl)oxy-, and Ci-β alkyl of said (C1-6 alkyl) optionally substituted, (C1 e alkyl)ox¡- optionally substituted is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, N(ReXRj, C1-4 alkoxy , phenyl, and optionally substituted 5-6 membered heteroaryl comprising at least one nitrogen or oxygen as a ring member; each R® is independently H or (C1-4 alkyl); and each Rfes is independently H, hydroxyl, or ( C1-4 alkyl). In some embodiments, the compound is of Formula (l-Bj, (ll-Bj, (l-bj, or (ll-bj, or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein RA2y RA1 are, each independently, H, halogen, hydroxyl, amino, amino(Ci-4 alkyl)-, (Ci-β alkyl) optionally substituted, or (C1-6 alkyl)oxy- optionally substituted, and C1-6 alkyl of said optionally substituted (Ci-βalkyl), optionally substituted (Ci-βalkyl)oxy- is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, N(ReXRj, C1-4 alkoxy, phenyl , and optionally substituted 5-6 membered heteroaryl comprising at least one nitrogen or oxygen as a ring member; and King Rfson, each independently, H or (C1-4 alkyl). LCQfrzn / zznz / q / viAi In some embodiments, the compound is of Formula (l-Bj, (ll-Bj, (l-bj, or (ll-bj, or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein at least one of RA2 or RA1 is independently H, halogen, hydroxyl, amino, amino(Ci-4 alkyl)-, (C1-6 alkyl) optionally substituted, or (0-6 to Iq uyl)oxy- optionally substituted, and the Ci ^ alkyl of said optionally substituted (C1-6 alkyl), optionally substituted (Ci-s alkyl)ox¡- is optionally substituted with 1-4 substituents, each independently selected from -N(R®)(Rj, tetrahydropyran, pyrrolidinyl , piperazinyl, piperidyl, and morpholinyl; each Rese independently selected from H (C1-4 alkyl), -(C14 alkyl)-NH2, and -(C1-4 alkyl)-Ci-4 alkoxy; and each Rfes independently H, hydroxyl , or (C1-4 alkyl). In some embodiments, the compound is of Formula (l-Bj, (ll-Bj, (l-bj, or (ll-bj, or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein at least one of RA2 or RA1 is independently H, halogen, hydroxyl, amino, amino(Ci-4 alkyl)-, (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxy- optionally substituted, and the C1-6 alkyl of said optionally substituted (Ci-βalkyl), optionally substituted (C1-6alkyl)oxy- is optionally substituted with 1-4 substituents, each independently selected from -N(Re)(Rj, tetrahydropyran, pyrrolidinyl, piperazinyl, piperidyl, and morpholinyl; each R® is independently H or (C1-4 alkyl); and each Rfes is independently H, hydroxyl, or (C1-4 alkyl). In some embodiments, the compound is of Formula (l-Bj, (ll-Bj, (l-bj, or (ll-bj, or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein at least one of RA2 or RA1 is independently H, halogen, hydroxyl, amino, amino(Ci-4 alkyl)-, (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxy- optionally substituted, and the C1-6 alkyl of said optionally substituted (C1-6 alkyl), optionally substituted (C1-6 alkyl)ox¡- is optionally substituted with 1-4 substituents, each independently selected from -N(R®)(Rj, tetrahydropyran, pyrrolidinyl, piperazinyl , piperidyl, and morpholinyl; and R® and Rfson, each independently, H or (C1-4 alkyl). In some embodiments, the compound is of Formula (l-Bj, (ll-Bj, (l-bj, or (ll-bj, or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein Yi, Y2, Z1 and Z2 are, each independently, O, S, C or N; Χι, X2, W1 and W2 are each independently C or N; X3 and X4 are, each independently, S or NRf; X5es N or CRA2; X6esNoCRA1; B is unsubstituted -C1-6 alkyl, or unsubstituted -C2-5 alkenyl; ra2 and raí are each independently, H, halogen, hydroxyl, amino, amino(Ci-4 alkyl)-, (C1-6 alkyl) optionally substituted, or (Ci-6alkyl)oxy- optionally substituted, wherein Ci-β alkyl of said (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxyoptionally substituted is optionally substituted with 1-2 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxy, -N(R ®)(Rj, CÜ2(Rj, unsubstituted phenyl, and unsubstituted 5-6-membered heteroaryl; R® is H, (C1-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), or -CO2(Ci-4 alkyl); LCQfrzn / zznz / q / viAi each occurrence of Rfes H, hydroxyl, or (C1-4 alkyl); R14 and RC2 are each independently absent, or are C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -OR°, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd; R16 and RC1, each independently, are absent, or are H or C1-4 alkyl; and R15, R17, R18, or R19 are each independently absent, or are H, C1-4 alkyl, wherein Ci-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; provided that at least one of (i), (i), or (iii) applies: (i) when (a) Zi, Z2, Yi and Y2 are each N, Wi, W2, Xi and X2 are each C; or (b) Wi, W2, Xi and X2 are each N, Zi, Z2, Yi and Y2 are each C; or (c) Zi and Yi are each N, Wi and Xi are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) Wi and Xi are each N, Zi and Yi are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or X9 is N; or (i) when (a) Ζι, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and SO2NRcRd, and -OCONRcRden where Rces H; or (iii) when (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of Xs, Xb, and )oxy-substituted, (C1-6 alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the Ci-e alkyl of said (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxy-substituted is optionally substituted with 1-2 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxy, -N(Re)(Rf), -CO^Rf ), unsubstituted phenyl, and unsubstituted 5-6-membered heterocycloalkyl; In some embodiments, the compound is of Formula (l-bj or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein Yi, Y2, Z1 and Z2 are, each independently, O, S, C or N; Xi, X2, W1 and W2 are, each independently, C or N; X3, X4 X5, Xe, and Xg are, each independently, as defined in Formula (lAj; B is unsubstituted -C2-5alkenyl-; RA2 and RA1 are, each independently, H, hydroxyl, (C1-6alkyl) optionally substituted, (Ci-6alkyl)oxy-optionally substituted, amino or amino(Ci-4alkyl)-, wherein the Ci-e alkyl of said (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxyoptionally substituted is optionally substituted with 1 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxy, and unsubstituted 5-6 membered heteroaryl , CQbzn / zznz / zi / YiAi R14 and RC2 are each independently absent, or are C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd; R16 and RC1, each independently, are absent, or are H or C1-4 alkyl; R15, R17, R18, or R19 are each independently absent, or are H, C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2Rc, -CONRcRd, -SO2NRcRd, and -OCONRcRd; provided that at least one of (i), (i), or (ii) applies: (i) when (a) Zi, Z2, Yi and Y2 are each N, Wi, W2, Xi and X2 are each C; or (b) Wi, W2, Xi and X2 are each N, Zi, Z2, Yi and Y2 are each C; or (c) Zi and Yi are each N, Wi and Xi are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) Wi and Xi are each N, Zi and Yi are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or X9 is N; or (i) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C, then R14 is a C1-4 alkyl substituted with halogen, -ORC, -NRcRd, -CO2Rc, -CONRcRd, - SO2NRcRd, and -OCONRcRden where Rces H; or (iii) when (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Xb, and - substituted, (C1-6 alkyl)amino- optionally substituted, or (C1-6 alkyl)(Ci-4 alkyl)amino- optionally substituted, wherein the Cy-ealkyl of said (C1-6 alkyl) optionally substituted or ( Substituted ci-ealkyl)oxy is optionally substituted with 1 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxy, and unsubstituted 5-6 membered heteroaryl. In some embodiments, the compound is of Formula (l-bj or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein Yi, Y2, Z1 and Z2 are each independently O, S, C or N; Xi, X2, W1 and W2 are, each independently, C or N; X3, X4, Xs, Xe, and X9 are each independently as defined in Formula (lAj; B is unsubstituted ethenyl; RA2y are each independently H, hydroxyl, amino, amino(Ci-4 alkyl)-, or optionally substituted (Ci-b alkyl)oxy-, wherein the Ci-β alkyl of said (C1-6 alkyl)oxy- optionally substituted is optionally substituted with hydroxyl; R14 and RC2 are each independently absent, or are C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd; R16 and RC1, each independently, are absent, or are H or C1-4 alkyl; and CQbzn / zznz / zi / YiAi R15, R17, R18, or R19 are each independently absent, or are H, C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2Rc, -CONRcRd, -SO2NRcRd, and -OCONRcRd; provided that at least one of (i), (i), or (iii) applies: (i) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, Xi and X2 are each N, Z1, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or X9 is N; or (i) when (a) Ζι, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C, then R14 is a C1-4 alkyl substituted with halogen, -ORC, -NRcRd, -CO2Rc, -CONRcRd, - SO2NRcRd, and -OCONRcRden where Rces H; or (iii) when (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Χε, and -, or optionally substituted (C1-6alkyl)ox¡-, wherein the Ci-βalkyl of said optionally substituted (Ci-6alkyl)ox¡- is optionally substituted with hydroxyl. In some embodiments, the compound is of Formula (l-bdj: R14 or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Yi, Y2, Z1 and Z2 are each independently O, S, C or N; Xi, X2, W1 and W2 are, each independently, C or N; X6esNoCRA1; X9 is N or CR4; X3, X4 X9, Rd, and Rfson, each independently, as defined herein; Reí and RC2 are, each independently, -CH2-, D is -halo(Ci-5alkyl), -C1-5 unsubstituted alkyl, or -C1-5alkenyl- unsubstituted; RB1 and RB2 are, each independently, -CH2-; B is -halo(Ci-5alkyl), -C1-5alkyl unsubstituted, or -Ci-salkenyl- unsubstituted; RA2 and RA1 are, each independently, H, halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, O-P(O)(OH)2, -O-P(O)(R'R)2, (C1-6 alkyl ) optionally substituted, or (C1-6 alkyl)oxy-optionally substituted, wherein the Ci-β alkyl of said (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxy-optionally substituted is optionally substituted with 1 -4 substituents, each independently selected from the group comprising hydroxyl, -O-P(O)(OH)2, -O-PIOXR'R^ C1-4 alkoxy, -NÍR^R1), -ΟΟΧΡ1), optionally substituted phenyl , and optionally substituted 5-6 membered heteroaryl; wherein said optionally substituted phenyl, or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(RIR) 2, amino, (Ci-6alkyl)amino-, (Ci-6alkyl)(Ci-6alkyl)amino, halo(Ci-6alkyl), hydroxy-(Ci-4alkyl)-, -(C1- 4 alkyl)-O-P(O)(OH)2, -(C1-4 alkyl)-O-P(O)(RlR)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2- 4 alkoxy)-, -(C2-4 alkoxy)-O-P(O)(OH)2, -(C1-4 alkoxy)-O-P(O)(RlR)2, -(C1-6 alkyl)-NH2, and C1-4alkoxy-(Ci-4alkoxy)-; Rese selected from H, (C1-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), -(C1-4 alkyl)-NH2, (C1-4 alkyl)-Ci-4 alkoxy, and -CO2(Ci-4 alkyl); R4y Rees H; R14 is absent, or is C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; R16 is absent, or is H or C1-4 alkyl; R15, R17, R18, or R19 are each independently absent, or are H, C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2Rc, -CONRcRd, -SO2NRcRd, and -OCONRcRd; and each R1 and R are independently (Ci-6alkyl)oxy-, provided that at least one of (i), (ii), or (iii) applies: (i) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or X9 is N; or (i) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and SO2NRcRd, and -OCONRcRden where Rces H; or (iii) when (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Χε, and I CQb7n / 77n7 / 3 / YIAI alkyl) optionally substituted, (C1-6 alkyl)oxy- substituted, (Ci-Balkyl)amino- optionally substituted, or (Ci-6 alkyl)(Ci-4 alkyl)amino- optionally substituted , wherein the (C1-6 alkyl) of said (C1-6 alkyl) optionally substituted, (Ci-s alkyl)ox¡- substituted, (C1-6 alkyl)amino- optionally substituted, or (0-6 alkyl) (Ci-4 alkyl)amino- optionally substituted is optionally substituted with 1-4 substituents each independently selected from hydroxyl, -O-P(O)(OH)z, -O-P^XR'R'jz, -N(Re)( Rj, -COz / Rj, -CON(Re)(Rf), optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1 -4 substituents, each independently selected from halogen, hydroxyl, -O-P(O)(OH)2, -O-P(O)(R'R)2, amino, (C1-6 alkyl)amino-, (Ci-s alkyl)(Ci-6 alkyl)amino-, -(C1-6 alkyl)-NH2, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(Ci4 alkyl)-O-P(O)( OH)2, -(C1-4 alkyl)-O-P(O)(RlR)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2. 4alkoxy)-O-P(O)(OH)2, -(C2-4alkoxy¡)-0-P(0)(RlR)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy- (Ci-4 alkoxy)-. In some embodiments, the compound is of Formula (l-bdj LCQfrzn / zznz / q / viAi R14 or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Υι, Y2, Z1 and Z2 are each independently O, S, C or N; Xi, X2, W1 and W2 are, each independently, C or N; X5es N or CRA2; X6esNoCRA1; X3, X4, Xg, Rd, and Rfson, each independently, as defined in Formula (IA); Reí and RC2 are, each independently, -CH2-; D is -halo(Ci-5alkyl), -C1-5 unsubstituted alkyl, or -C2-5alkenyl- unsubstituted; RB1 and RB2 are, each independently, -CH2-; B is -halo(Ci-5alkyl), -C1-5unsubstitutedalkyl, or -C2-5alkenyl-unsubstituted; RA2y are independently caqauno, H, halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, (C1-6 alkyl) optionally substituted, or (Ci-6alkyl)oxy-optionally substituted, where the Ci-β alkyl of said optionally substituted (C1-6 alkyl), or (C1-6 alkyl)oxyoptionally substituted is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxy, - Ν^χΡ1) , CO2(Rf), optionally substituted phenyl, and optionally substituted 5-6 membered heteroaryl; wherein said optionally substituted phenyl, or 5-6 membered heteroaryl is optionally substituted with 14 substituents, each independently selected from halogen, hydroxyl, amino, (C1-6 alkyl)amino-, (C1-6 alkyl)(C1- 6 alkyl)amino-, halo(C1-6 alkyl), hydroxy-(Ci-4 alkyl)-, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, and C1-4 alkoxy-(Ci-4 alkoxy)-; Rese selected from H, (C1-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), and -CO2(Ci-4 alkyl); R4 and R6 are H; R14 is absent, or is C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; R16 is independently absent, or is H or C1-4 alkyl; and R15, R17, R18, or R19 are each independently absent, or are H, C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2Rc, -CONRcRd, -SO2NRcRd, and -OCONRcRd; provided that at least one of (i), (i), or (iii) applies: (i) when (a) Ζι, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Ζι, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or Xg is N; or (i) when (a) Ζι, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and , -SO2NRcRd, and -OCONRcRden where Rces H; or (iii) when (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of Xs, Xe, and alkyl)oxy-substituted, optionally substituted (C1-6 alkyl)(Ci-4 alkyl)amino-, wherein the Ci-β alkyl of said optionally substituted (C1-6 alkyl) , or substituted (C1-6 alkyl)ox¡- is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxy, -N(Re)(Rj, -CO^R1) , optionally substituted phenyl, and optionally substituted 5-6 membered heteroaryl; wherein said optionally substituted phenyl, or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (C1-6 alkyl)amino-, (C1-6 alkyl)( C16 alkyl)amino-, halo(C1-6 alkyl), hydroxy-(Ci-4 alkyl)-, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4alkoxy), and C1- 4alkoxy-(Ci-4alkoxy)-. In some embodiments, the compound is of Formula (l-bd j or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein Xg is CR4. LCQfrzn / zznz / q / viAi In some embodiments, the compound is of Formula (l-bd j, or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein RA2 and RA1 are, each independently, H, halogen, hydroxyl, amino, amino (Ci-4 alkyl)-, (C1-6 alkyl) optionally substituted, or (Ci-6 alkyl)oxy- optionally substituted, and the Ci-ealkyl of said optionally substituted (C1-6 alkyl), (C1-6 alkyl) optionally substituted )ox¡- is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, -O-P(O)(OH)z, -OP(O)(RIR)2, -Ν(Ρ ®)(Ρ*), Ci e alkoxy, phenyl, and optionally substituted 5-6 membered heteroaryl comprising at least one nitrogen or oxygen as a ring member; each R® is independently selected from H, -(Ci-4 alkyl)-NH2, and -(C1-4 alkyl)-Ci-4 alkoxy; and each Rfes independently H, hydroxyl, or C1-4 alkyl. In some embodiments, the compound is of Formula (l-bd j, or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein RA2 and RA1 are, each independently, H, halogen, hydroxyl, amino, amino (Ci-4 alkyl)-, (O-b alkyl) optionally substituted, or (C1-6 alkyl)oxy- optionally substituted, and the C1-6alkyl of said (C1-6 alkyl) optionally substituted, (C1-6 alkyl)oxy - optionally substituted is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, -N(Re)(Rf), C1-4 alkoxy, phenyl, and optionally substituted 5-6 membered heteroaryl comprising at least one nitrogen or oxygen as a ring member; each R® is independently H or (C1-4 alkyl); and each Rfes is independently H, hydroxyl, or (C1-4 alkyl). In some embodiments, the compound is of Formula (l-bd j, or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein RA2 and RA1 are, each independently, H, halogen, hydroxyl, amino, amino (Ci-4 alkyl)-, optionally substituted (C1-6 alkyl), or optionally substituted (C1-6 alkyl)oxy-, and the Οι-ealkyl of said optionally substituted (C1-6 alkyl), (Ci e alkyl) oxy-optionally substituted is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, -N(Re)(Rf), C1-4 alkoxy, phenyl, and optionally substituted 5-6 membered heteroaryl comprises at least one nitrogen or oxygen as a ring member; and R® and Rfson, each independently, H or (C1-4 alkyl). In some embodiments, the compound is of Formula (l-bd j, or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein at least one of RA2 or RA1 is independently H, halogen, hydroxyl, amino, amino (Ci-4 alkyl)-, (C1-6 alkyl) optionally substituted, or (C1-6 alkyl)oxy- optionally substituted, and the Ci-ealkyl of said (Cvb alkyl) optionally substituted, (C16 alkyl)oxy- optionally substituted is optionally substituted with 1-4 substituents, each independently selected from -N(R®)(Rf), tetrahydropyran, pyrrolidinyl, piperazinyl, piperidyl, and morpholinyl; each R® is independently selected from H (C1-4 alkyl) , -(C1-4 alkyl)-NH2, and -(C1-4 alkyl)-Ci-4 alkoxy; and each Rfes independently H, hydroxyl, or (C1-4 alkyl). In some embodiments, the compound is of Formula (l-bd j, or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein at least one of RA2 or RA1 is LCQfrzn / zznz / q / viAi independently H, halogen, hydroxyl, amino, amino(Ci-4 alkyl)-, (0-6 alkyl) optionally substituted, or (Ci e alkyl)oxy- optionally substituted, and Ci-ealkyl of said optionally substituted (C1-6 alkyl), optionally substituted (Ci e alkyl)oxy- is optionally substituted with 1-4 substituents, each independently selected from -N(Re)(Rj, tetrahydropyran, pyrrolidinyl, piperazinyl, piperidyl, and morpholinyl; each Rees independently H or (C1-4 alkyl); and each Rfes independently H, hydroxyl, or (C1-4 alkyl). In some embodiments, the compound is of Formula (l-bd j, or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein at least one of RA2 or RA1 is independently H, halogen, hydroxyl, amino, amino (Ci-4 alkyl)-, (0-6 alkyl) optionally substituted, or (Ove alkyl)oxy- optionally substituted, and the Ci-βalkyl of said (0-6 alkyl) optionally substituted, (Ci-6 alkyl)ox ¡- optionally substituted is optionally substituted with 1-4 substituents, each independently selected from -N(R®)(Rj, tetrahydropyran, pyrrolidinyl, piperazinyl, piperidyl, and morpholinyl; and Rey Rfson, each independently, H or (C1- 4 alkyl). In some embodiments, the compound is of Formula (Vj is a compound of Formula (V-a), (V-b), (V-c), (V-d), (V-e), (V-e1), (V-e2), (V-f), (V-f1), (V-f2), (V-f3), (V-f4), (V-f5), (V-f6), (V-f7), (V-g), (V-g1), (V-g2), (V-g3), (V-g4), (V-g5), (V-g6), (V-g7), (V-h), (V-h1 ), (V-h2), (V-h3), (V-h4), (V-h5), (V-h6), (Vh7), (V-i), (V-¡1), (V- ¡2), (V-I3), (V-¡4), (V-Í5), (V-¡6), or (V-I7). In some embodiments, the compound is of Formula (Vj, wherein the compound is of Formula (V-a), Formula (V-b), Formula (V-c), Formula (V-d), Formula (V-e), Formula (V-e1 ), or Formula (Ve2): or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Yi, Y2, Zi, Z2, Xi, X2, Wi, W2, X5,X6, Xs, X3, , each independently, as defined in Formula (Vj; and ra2 and rootquanc|o are present, are, each independently, halogen, hydroxyl, (C1-6 alkyl) optionally substituted, (0-6 alkyl)ox¡ - substituted, (Ci-e alkyl)amino- optionally substituted, or (Οι-e alkyl)(Ci-4alkyl)amino- optionally substituted, wherein the Οι-e alkyl of said (Ci-e alkyl) optionally substituted, or Substituted (C1-6 aIkyl)ox¡- is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxy, -N(Re)(Rj, -CC^Rj, -CON ^XRj, and -COOH. In some embodiments, the compound is of Formula (V-a), Formula (V-b), Formula (Vc), Formula (V-d), Formula (V-e), or Formula (V-e2), where Xs is CH. In some embodiments, the compound is of Formula (Vj, where the compound is of Formula (V-f), Formula (V-f1), Formula (V-f2), Formula (V-f3), Formula (V- f4), Formula (V-f5), Formula (V16), or Formula (V-f7): LCQfrzn / zznz / q / viA or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Y2 and Z2 are, each independently, O, S, C or N; X2 and W2 are, each independently, C or N; X3, X4, Xs, Xe, RC2 each independently are absent, or are C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, the compound is of Formula (V-f), Formula (V-f1), Formula (Vf2), Formula (V-f3), Formula (V-f4), Formula (V-f5), or Formula (V-f6), where X9 is CH. In some embodiments, the compound is of Formula (Vj, where the compound is of Formula (V-g), Formula (V-g1), Formula (V-g2), Formula (V-g3), Formula (V- g4), Formula (V-g5), Formula (V-g6), or Formula (V-f7): LCQfrzn / zznz / q / viA LCQfrzn / zznz / q / viA or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Y2 and Z2 are each independently O, S, C or N; X2 and W2 are, each independently, C or N; X3, X4, Xs, Xe, and RC2 is absent, or is C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RG, -CONRcRd, -SO2NRGRd, and -OCONRcRd. In some embodiments, the compound is of Formula (V-g), Formula (V-g1), Formula (Vg2), Formula (V-g3), Formula (V-g4), Formula (V-g5), or Formula (V-g6), where Xg is CH. In some embodiments, the compound is of Formula (V'), where the compound is of Formula (V-h), Formula (V-h1), Formula (V-h2), Formula (V-h3), Formula ( V-h4), Formula (V-h5), (Formula (V-h6), or Formula (V-h7): R14 or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Yi and Zi are, each independently, O, S, C or N; Xi and Wi are, each independently, C or N; Xs, Xe, Χθ, X3, and R14 is absent, or is Ci-4alkyl, where Ci-4alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd. In some embodiments, the compound is of Formula (V-h), Formula (V-h1), Formula (Vh2), Formula (V-h3), Formula (V-h4), Formula (V-h5), or ( Formula (V-h6), where Xg is CH. In some embodiments, the compound is of Formula (Vj, where the compound is of Formula (V-¡), Formula (V-Í1), Formula (V-¡2), Formula (V-I3), Formula (V-I4), Formula (V-¡5), (Formula (V¡6), or Formula (V-¡7): LCQfrzn / zznz / q / viAi LCQfrzn / zznz / q / viA or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Xg, X3, X4, Xs, In some embodiments, the compound is of Formula (V-¡), Formula (V-¡1), Formula (V¡2), Formula (V-¡3), Formula (V-¡4), Formula ( V-¡5), or Formula (V-¡6), where Xg is CH. In some embodiments, when the compound of Formula (Vj is of Formula (V-c), Formula (V-f), Formula (V-g), Formula (V-h), Formula o (V-¡), at least one of X3 and X4 is S or at least one of X5, Xe and Xg is N. In some embodiments, when s is 0 and r is 1, then at least one of X3 and X4 is S or at least one of Χε, Χε and Χθ is N. In some embodiments, at least one of X3 and X4 is S or at least one of Χε, Χε and X9 is N. In some embodiments, at least one of X3 and X4 is S. In some embodiments, at least one of Xs, Χε and X9 is N. In some embodiments, Xs, Χε, and X9 are each CH and X3 and X4 are each N. In some embodiments, Xs, Χε, and Xg are each CH; X3 is S; and X4 is N. In some embodiments Xs and Xg are each CH and Χε, Xs, and X4 are each N. In some embodiments, Xs and Xg are each CH; Xe and X4 are each N; and X3 is S. In some embodiments, Xs and Xg are each CH; Xe and X3 are each N; and X4 is S. In some embodiments, Xs is CH; Χε, X4, and Xgson, each, N; and Xses S. In some embodiments, the compound of the invention is not selected from: LCQfrzn / zznz / q / viA 100 LCQfrzn / zznz / q / viAi 101 In some embodiments, the compound of the invention is not: (E)-N,N'-(but-2-ene-1,4-d¡lb¡s(5-carbamo¡l-7-(2-hydroxy¡ethoxy¡)-1H-benzo[d] m¡dazol-1,2-diyl))bis(4-ethyl-2-methyloxazole-5-carboxamide); 102 (E)-N,N'-(but-2-ene-1,4-d¡lb¡s(5-carbamoyl-7-hydroxy¡-1 H-benzo[d]imidazole-1, 2-diyl))bis(4-ethyl-2methyloxazole-5-carboxamide); (E)-N-(5-carbamoyl-1-(4-(5-carbamoyl-2-(4-ethyl-2-methyloxazole-5-carboxamido)-7-hydroxyl- 1Hbenzo[d]¡m¡dazol-1-yl)but-2-en-1-yl)-7-methoxy¡-1H-benzo[d]¡m¡dazol-2-¡l)-4-et¡ l-2-methyloxazole-5-carboxamide; N,N'-((((1 S,2S)-cyclopropane-1,2-diyl)bis(methylene))bis(5-carbamoyl-1 H-benzo[d]imidazole-1 ,2diyl))bis(4-ethyl-2-methyloxazole-5-carboxamide); (E)-1,1'-(but-2-ene-1,4-d¡l)bs(2-(2,5-dimet¡lfuran-3-carboxamido)-7-methox ¡-1 H-benzo[d]imidazole5-carboxamide); (E)-N,N'-(hex-3-ene-1,6-di¡lb¡s(5-carbamo¡l-1H-benzo[d]ímidazol-1,2-diyl))bis( 4-ethyl-2-methyloxazole5-carboxamide); (E)-N-(5-carbamoyl-1-(4-(5-carbamoyl-2-(4-ethyl-2-methyloxazole-5-carboxamido)-1H-benzo[d]) mídazol1-yl)but-2-en-1-yl)-7-methyl-1 H-benzo[d]imidazol-2-yl)-4-ethyl-2-methyloxazol-5-carboxamide; (E)-N-(5-carbarnoyl-1-(4-(5-carbamoyl-2-(2,4-dimethyloxazol-5-carboxamido)-1H-benzo[d]imidazole-1¡l)but-2 -en-1-yl)-7-methyl¡l-1H-benzo[d]m¡dazol-2-¡l)-2,4-dimethyloxazole-5-carboxamide; (E)-N,N'-(but-2-ene-1,4-di¡lb¡s(5-carbamo¡l-7-methox¡-1 H-benzo[di]imidazole-1,2- diyl))bis(2,4dimethyloxazole-5-carboxamide); (E)-N,N'-(but-2-ene-1,4-di¡lb¡s(5-carbamoyl-7-methox¡-1H-benzo[di]imidazol-1,2-diyl) )bis(4-ethyl-2-methyloxazole-5-carboxamide); (E)-1 ,T-(but-2-ene-1,4-diyl)bis(2-(1-ethyl-1H-imidazole-5-carboxamido)-7-methoxy-1Hbenzo[d]imidazole-5 -carboxamide); (E)-1,T-(but-2-ene-1,4-diyl)bis(2-(1-ethyl-1H-midazole-2-carboxamido)- 7-methoxy¡-1Hbenzo[d]imidazole-5-carboxamide); (Z)-4-Carbamoyl-1,15-bis(4-ethyl-2-methyloxazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10dioxa-acid 2,14,15a,19a-tetraazac¡clopentadeca[3,2,1-cd:8,9,10-c'd']di¡ndene-12-carboxylic; (E)-1-(4-(5-carbamoyl-2-(furan-2-carboxamido)-1H-benzo[d]imidazol-1-yl)but-2-en-1-yl) -2-(furan-2carboxamido)-7-methyl-1H-benzo[d]imidazole-5-carboxamide; (E)-1 -(4-(5-carbamoyl-2-(pyrazolo[1,5-a]pyridine-2-carboxamido)-1 H-benzo[d]imidazole-1 -i I) but-2-e n1 -yl)-7-methyl-2-(pyrazolo[1,5-a]pyridine-2-carboxamido)-1 H-benzo[d]imidazole-5-carboxamide; (E)-1-(4-(5-carbamoyl-2-(1-methyl 1-1 H-pyrrole-2-carboxamido)-1H-benzo[d]imidazol-1-yl)but-2-en- 1-yl)7-methyl-2-(1 -methyl-1 H-pyrrole-2-carboxamido)-1 H-benzo[d]imidazole-5-carboxamide; (E)-1 -(4-(5-carbamoyl-2-(1 H-pyrrole-2-carboxamido)-1 H-benzo[d]imidazol-1 -yl)but-2-en-1 -yl) -7-methyl2-(1H-pyrrole-2-carboxamido)-1H-benzo[d]midazole-5-carboxamide; (E)-1-(4-(5-carbamoyl-2-(1-methyl 1-1 H-indol-2-carboxamido)-1H-benzo[d]imidazol-1-yl)but-2-en -1-yl)7-methyl-2-(1 -methyl-1 H-indole-2-carboxamido)-1 H-benzo[d]imidazole-5-carboxamide; (E)-N-(5-carbamoyl-1-(4-(5-carbamoyl-2-(4-ethyl-2-methyloxazole-5-carboxamido)-7-(3-hydroxypropoxy)1H-benzo[ d]imidazol-1-yl)but-2-en-1-yl)-7-methoxy-1H-benzo[d]imidazol-2-yl)-4-ethyl-2-methyloxazole-5carboxamide; LCQfrzn / zznz / q / YiAi 103 (Z)-1,15-bis(4-ethyl-2-methyloxazole-5-carboxamido)-8,9,16,19-tetrahydro-7H-6,10-dioxa- 2,14,15a,19atetraazacyclopentadeca[3,2,1-cd:8,9,10-c'd']d¡ndene-4,12-dicarboxamide; N-(5-carbamoyl-1 -(2-((1 R,2R)-2-(2-(5-carbamoyl-2-(4-ethyl-2-methyloxazole-5-carboxamido))- 1 Hbenzo[d]¡m¡dazol-1-yl)et¡l)cyclopropyl)et¡l)-7-methyl-1H-benzo[d]¡m¡dazol-2-¡l)- 4-ethyl-2-methyloxazole-5carboxamide; (E)-N-(5-carbamoyl-1-(4-(5-carbamoyl-2-(4-ethyl-2-methyloxazole-5-carboxamido)-7-(2-hydroxyethoxy¡)-1Hbenzo[ d]¡m¡dazol-1-¡l)but-2-en-1-yl)-7-methoxy¡-1H-benzo[d]¡mádazol-2-¡l)-4-ethyl -2-methyloxazole-5-carboxamide; (E)-2-((5-carbamoyl-1-(4-(5-carbamoyl-2-(4-ethyl-2-methyloxazole-5-carboxamido)-7-methox) acid ¡-1Hbenzo[d]¡m¡dazol-1-¡l)but-2-en-1-yl)-2-(4-ethyl-2-methyloxazole-5-carboxam¡do)-1H -benzo[d]¡m¡dazol-7yl)oxy)acetic acid; Acid (E)-2-((5-carbamoyl-1-(4-(5-carbamoyl-2-(4-ethyl-2-methyloxazole-5-carboxamido)-7-(2hydroxy) ethoxy)-1H-benzo[d]imídazol-1-íl)but-2-en-1-íl)-2-(4-ethyl-2-methyloxazol-5-carboxamido)- 1Hbenzo[d]imidazol-7-yl)oxy)acetic acid; (E)-1,15-bis(4-ethyl-2-methyloxazole-5-carboxamido)-N-(2-hydroxyethyl)-8,9,16,19-tetrahydro -7H-6,10dioxa-2,14,15a,19a-tetraazac¡clopentadeca[3,2,1-cd:8,9,10-c'd']d¡ndene-4,12-d¡carboxam gives; (E)-N-(5-carbamo¡l-1-(4-(5-carbamo¡l-2-(4-ethyl-2-methyloxazole-5-carboxam¡do)-7-methox ¡-1Hbenzo[d]¡m¡dazol-1-yl)but-2-en-1-¡l)-7-(2-(dimethyl¡lamino)ethoxy¡)-1H-benzo[d]¡m¡ dazole-2-íl)-4-ethyl-2-methyloxazole5-carboxamide; or (E)-1 -(4-(5-carbamoyl-2-(1 -(2-h id roxyethyl)-3-methyl-1 H-pyrazole-5-carboxamido)-1 H-benzo[d] imidazol1 -yl) but-2-e n-1 -i 1)-2-(1 -ethyl I-3-methyl-1 H-pyrazol-5-carboxamido)-1 H-benzo[d]imidazol-5- carboxamida. Representative compounds of this invention include the compounds of the Examples. It will be appreciated that the present invention encompasses the compounds of Formula (I'), Formula (IA'), Formula (II'), Formula (III'), Formula (IV'), and Formula (V') as the free base and as salts thereof, eg, as a pharmaceutically acceptable salt thereof. In some embodiments, the invention relates to the compounds of Formula (I'), Formula (IA'), Formula (II'), Formula (ΙΙΓ), Formula (IV'), and Formula (V') in form of a free base. In some embodiments, the invention relates to compounds of Formula (I'), Formula (IA'), Formula (II'), Formula (III'), Formula (IV'), and Formula (V'). in the form of a salt; particularly, a pharmaceutically acceptable salt. It will further be appreciated that, in some embodiments, the invention relates to the compounds of the Examples in the form of a free base. In some embodiments, the invention relates to the compounds of the Examples in the form of a salt, particularly, a pharmaceutically acceptable salt. In some embodiments, in the compound of Formula (I'), (ΙΑ'), (ΙΙΓ), (IV), (V'), (l-B'), (Ιό'), (ll-B '), (ll-b'), (V-a), (V-b), (V-c), (V-d), (V-e), (V-e1), (V-e2), (V-h), (V-h1 ), (V-h2), (V-h3), (V-h4), (V-h5), (V-h6), or (V-h7), Ring 1 is selected from any one of the following : 104 where: LCQfrzn / zznz / q / viAi R14, R15, R19 and RC1 are each independently H, C1-4 alkyl, halogen or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is substituted with a halogen or -CO2H. In some embodiments, the C1-4 alkyl is methyl or ethyl. In some embodiments, the C1-4 alkyl is methyl substituted with -COOH. In some embodiments, in the compound of Formula (I'), (ΙΑ'), (III'), (IV'), (V'), (l-B'), (Ιό'), (ll -B'), (ll-b'), (V-a), (V-b), (V-c), (V-d), (V-e), (V-e1), (V-e2), (V-f), (V -f1), (V-f2), (V-f3), (V-f4), (V-f5), (V16), (V-f7), (V-g), (V-g1), (V -g2), (V-g3), (V-g4), (V-g5), (V-g6), or (V-g7), Ring 2 is selected from any one of the following: 105 (1) p18 <ϊ R16 . (2) RC2 *N^R17 . ννΨΛΛ .A. z=< OO 00 I heard X z-z / \\ co vX -o 3 wvw» z=z (6) RC\ N^R17. (7) RC2 R18 XX Rl6 . (8) ς X8 KX R16 . (9) j / 'N -rX. J1 r^R17 R16 - (10) RC2 , Xn^R18 -Kx r^R17 R16 . N 09 (12) s s^R18 r^R17 R16 ; (13) \| R18 “K X N^r17 . (14) □ C2 ík N^r17. (15) RC\ V .R18 -KX N r17 (16) _L / °'N r^R17 R16 (17) R“ iA i r^R17 R16 ; (18) RC2 ξ / / 0 ^r^R17 R16 ; (19) R“ § ^S ^t^r17 R16 ; (20) □C2 Y R18 ^t^r17 R16 ; wuw» (22) r^R17 R16 · (23) ΗI J R16 ; (24) RC2 N T\ Í N-^r17 R16 and (25) p18 . N-^ / K χχ rZ16 where: R16, R17, R18 and RC2 are each independently H, C1-4 alkyl, halogen or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is substituted with a halogen or -CO2H. In some embodiments, one or more of R16, R17, R18, and RC2 is methyl, ethyl, or -COOH substituted methyl, provided that, when r is 1, s is 0, Ring 1 is then at least one of X3 and X4 is S or at least one of Xs, Xe, and X9 is N. In some embodiments, one or more of R16, R17, R18, and RC2 is methyl, ethyl, or methyl substituted with -COOH, 106 R14 R16 LCQfrzn / zznz / q / YiAi provided that, when r is 1, s is 0, Ring 1 is rC1 and Ring 2 is then at least one of X3 and X4 is S or at least one of Xs, Xs, and Xs is N In some embodiments, Ring 1 and Ring 2 are each independently selected from any one of the following: (1) (2) (3) i· (4) J>'N “<^11 (5) _ly°'N (6) (7) ¿ / ^0 A ; (8) £ (9) (10) > Am (11) \ jN-n —5—II V-N ; (12) -kNj N ; (13) H (14) X -f-yii (15) N ; (16) Au / ; (17) 0 ^OH s / N'N nu (18) N ; (19) , nL Ay (20) Ay (21) (22) (23) S- / i· (24) ξ ZS^N (25) / SN (26) (27) (28) nA.· (29) ) <r; (30) 107 (31) . NA3 A ; (32) s / ^0 (33) (34) (35) aI J N ; ío \ a ^=Z (37) A π (38) H a ii An (39) $ (40) ξ ^-s (41) ξ ^NH (42) ú Ή_^ν (43) A (44) An nA (45) k?: (46) N-ν' A (47) o^ Al. (48) a ii ? \^N (49) (50) g ​​Ά (51) .0 HO^ g zNN i Ají (52) HO * g An ’ vX (53) HO • g An ! yjl (54) HO ? g N'N i chili pepper (55) g N'N i Chili pepper (56) .0 HO- / ' 0 g / A i Ah (57) HO 0 oz ? AN i Ají ; and (58) HO ^=0 g zN'N i Ah i cobzn / zznz / zi / Yl· In some embodiments, the compounds of the invention are selected from the compounds set forth in Table 1, or a tautomer thereof, or a prodrug thereof, or a salt thereof, particularly a pharmaceutically acceptable salt thereof. themselves. Table 1 LCQfrzn / zznz / q / YiAi Example No. Compound No. Structure LCMS (M + H)+ 1 9 2 o HzN .O / _ _ \\ HCT^^O / I 783.30 2 10 I I O Z \ I? M \ l 1 \ / ω z=^ h 815.20 3 11 I I O Z \ 1? 1 i go ri ' * 781.20 109 Example No. Compound No. Structure LCMS (M + H)+ 4 12 I I O Z \ r? 727.30 5 13 hJ yA 2 ü 1 N=< HCT O / 0 0 755.10 6 14 9 o μι ]l ] 2 [f jT Άνη J9 HO O / Η N JL JL \H H2N\^y^-N ¿ J¡ Ί O 0 799.20 i cobzn / zznz / zi / Y 110 Example No. Compound No. Structure LCMS (M + H)+ 7 15 2 o n!, N HO ^^O / 0 0 N 781.40 8 16 2 O ^jí^N .0 / _ _ \\ rA^N \ h n 1 L N\H η2ν^>^>-ν \ / y Π / V-N 753.15 9 ​​17 2 o s^ / cf3 HzN Í^VnV^*1 HO ^^O / ί<=ί^χ<Ν u μ 1 l[ —NH S^zCF3 h2n^An 0 0 867.05 i cobzn / zznz / zi / Y 111 Example No. Compound No. Structure LCMS (M + H)+ 10 18 9 οθ'- / H2nAtvVnhVn h2n ^^ o / I 782.38 11 19 9 o HzN XxX / x Xo / HO. / Π 0 \ 0 u m 1 U / XNH O- / I <Q-n 811.30 12 26 I °ν^Ν'° H2N Ü^Vnh^ _ / HO O / 0 o 697.26 I CQb7n / 7?n7 / =l / Y 112 i cobzn / zznz / zi / Y Example No. Compound No. Structure LCMS (M + H)+ 16 37 OS-y-' d] HO — O / T O^N 799.20 17 38 X °On'n HzN vTVníAK ^í^N d HO^^O / dd Ϊ >7 798.30 18 39 s s £ < z. or iT 781.20 I CQfr7n / 77n7 / □ / Y 114 i cobzn / zznz / zi / Y 115 Example No. Compound No. Structure LCMS (M + H)+ 22 43 2 0 HzN HO ^^O / 0 ° 782.30 23 51 I ovJ^~n ^ ΓΤΥνη _ / HO 0 / h+JJYhY I o^n 752.30 24 52 τ A vJ / O— τ \ Z X \ M O I T 768.20 I CQfr7n / 77n7 / □ / Y 116 Example No. Compound No. Structure LCMS (M + H)+ 25 53 or < j? V / n~n l-l / v. Q 2 T i χ^νη HO ^^O / 0 o x 751.25 26 63 9 ox HzN yV >NbN 0 / rí^V'N IT / )—NH 0^ / 800.20 27 64 9 (D 0-^ y—ll ΗζΝ^γγ^,ΑΛ^Ν ^r'N HO O / 1¡ / )—NH 0^ 772.20 i cobzn / zznz / zi / Y i cobzn / zznz / zi / Y 118 Example No. Compound No. Structure LCMS (M + H)+ 31 68 A °On'n Y^N »^7 o YY Y hY7y 0 0 826.30 32 69 X 17 Η2ΝΥ3>νΥ^\ Y>Y ,Υ HO 0 / RVN I |T YNH OY h2nYY \ / Y II YYn 0 u __ / 799.30 33 70 Y>Y „Y | |T Ynh sy h2n ΥΛν νγ Y Π Yp 0 u __ / 816.20 i cobzn / zznz / zi / Y 119 Example No. Compound No. Structure LCMS (M + H)+ 34 71 A 'Ύ' HzN VTs>=k^A ^í^N 0 / / ^N \ HN L / N'N O or N^ 799.30 35 72 A VJ'-N ] HO 0 / z^N || / )—NH O^ / H2NsAAN / VhC Y π ^fyN 0 ° / 785.20 36 73 2 o ££ s r—ll HzN nS^r \¡^-N ,° / \\ r^Y<N \ HN Λν HzN yV^N yY ¡I II 0 799.30 i cobzn / zznz / zi / Y 120 Example No. Compound No. Structure LCMS (M + H)+ 37 74 ° o UN JL ς y—<\ 11 ΠZ Y HO 0 X Jx^N ¡A Η N 11 / N ' Η2Νγ\Ζ-Ν V-ά N 0 0 822.25 38 75 o < S °<z A^N / HO ^^ O / ΥΑΤ / ι0 0 0 772.30 39 76 ° c> s^z HzN [Ύ>=νΎν V^N HO O / (Z^ r-N II / )—NH O^Z y / Y I ο^ΥΝ o ° Γ 816.20 i CQbzn / zznz / zi / Y 121 Example No. Compound No. Structure LCMS (M + H)+ 40 84 Ϊ 2 Ύ 1 J o ° 679.20 41 85 9 o o- / ^N^N J í |T >— NH 0^ / 681.10 42 89 ? O*'N HjN bTVnh / ) Br / N Λ O o 757.20 I CQfr7n / 77n7 / □ / Y 122 Example No. Compound No. Structure LCMS (Μ + H)+ 43 90 \=z ° A ZZ A )= / < / z ¿ λλ °A ^Vo z I £ 758.10 44 94 j? %ΑΝ H2N 0 / Α\-Ν \ H^nJU^HAn 0 o 752.30 45 95 2 o o-- / -'n^'n i HO 0 / ζΑχ-'Π η2ν^Ιν^Χ I ό^Ν 754.25 i cobzn / zznz / zi / Y 123 i cobzn / zznz / zi / Y 124 i cobzn / zznz / zi / Y 125 i cobzn / zznz / zi / Y 126 Example No. Compound No. Structure LCMS (M + H)+ 116 HíN Π HO^^O / 0 0 N-X 798.33 117 z= / x / A 1 't Z o^z π z O W Z^\í=< e « £ < o χ T 798.24 118 N O'N HzN fYVnIAV ^n^n ) HO 0 / HzN^jCN^NtL / -O o o 726.31 i cobzn / zznz / zi / Y 127 i cobzn / zznz / zi / Y 128 Example No. Compound No. Structure LCMS (M + H)+ 122 4 ° A tN ( Z O X X 752.34 i cobzn / zznz / zi / Y 129 Example No. Compound No. Structure LCMS (M + H)+ 125 d 4 ° A / ( O I X 766.34 126 % í¿ FU \x ) >° M o i ' 1 L ZAnH p^ Π r 0 0 727.21 i cobzn / zznz / zi / Y 130 i cobzn / zznz / zi / Y 131 I CQb70 / 77(17 / □ / Y 132 Example No. Compound No. Structure LCMS (M + H)+ 134 ^'N H2N^^ N II T I x>—NH YVN Λ 0 0 680.26 135 0. H2N.^. Ν Μ\ π YY ^iQn γΎ _Y YÁ O / a L £^nxh pv 2T^N 755.27 136 9 o ζθγ^ H2N \Á^N __ / ,γ / HO O / A L £ N\H / °'ΎΧ Π / ^YN O 0 755.23 i cobzn / zznz / zi / Y 133 Example No. Compound No. Structure LCMS (M + H)+ 137 2 O'N h y £ ΆΝΗ y < ΑγΝ Y 0 θ- 736.28 138 2 o P- / H2N A^n __ / ,γ HO^^O / 0 0 741.21 139 2 o ογ HzN OH / > OH / u μ 1 U / XNH o-x h2nA%An Y I ¿yA 711.12 i cobzn / zznz / zi / Y 134 I CQb7n / 77n7 / =l / Y 135 Example No. Compound No. Structure LCMS (Μ + Η)+ 143 2 o O / ϊ ο^Ν 770.13 144 2 ο H2N^¥^VnhVn ^ν^ν — / _ _ {dd Η Ν JL L / 3^ I Ο^Ν 786.10 145 2 o s^ / H2N^YYS>ñ^Vn ^ν^ν Ο / I Ο^Ν I CQb70 / 77(17 / □ / Y 136 Example No. Compound No. Structure LCMS (M + H)+ 50 146 9 o HO ^^O / ζΛγΝ I Ó^N 771.30 147 A A A T \ / Ui <ñ- O X T 769.13 50a 148 HzN FTVnH ^n^n — / HO ^^O / h2n I ό^Ν 770.13 i cobzn / zznz / zi / Y 137 I CQb7n / 77n7 / =l / Y 138 i cobzn / zznz / zi / Y 139 Example No. Compound No. Structure LCMS (M + H)+ 155 9 Q_.0^ / N — today^° / O ^k^-N I 799.11 51 167 'Μ >=Z ° T\ ύΊ ° Λ Η H + ; / CN \ Z I \ CN O I CQb7n / 77n7 / □ / Y 140 In some embodiments, the compounds of the invention are the compounds: LCQfrzn / zznz / q / Yi 141 LCQfrzn / zznz / q / viAi 142 LCQfrzn / zznz / q / viA 143 144 LCQfrzn / zznz / q / YiA or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof. In some embodiments, the compounds of the invention are the compounds: 145 LCQfrzn / zznz / q / viA 146 LCQfrzn / zznz / q / YiA or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof. In some embodiments, the compounds of the invention are the compounds: 147 LCQfrzn / zznz / q / viA or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof. In some embodiments, the compound of the invention is Example No. 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 38, 39, 40, 41,42, 43, 44, 45, 46, 47, 48, 49, 50, 50a, 51, or 52 or Compound No. 111, 112, 113, 114, 115, 116, 117, 118, 120, 121,122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 14 0, 141, 142, 143, 144, 145, 147, 149, 150, 151, 152, 153, 154, 155, or 182. In some embodiments, the compound of the invention is Example No. 1,2, 3, 4 , 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23, 24, 25, 26, 27, 28, 29 , 30, 31,32, 33, 34, 35, 36, 38, 39, 40, 41, 42, 43, 44, 45,46,47, 48, or 49, or Compound No. 111, 112, 113, 114, 115, 116, 117, 118, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138. In some embodiments, the compound of the invention is Compound no. 140, 141, 142, 143, 144, 145, 146, 147, 148, 149,150, 151, 152 or 153. In some embodiments, the compound of the invention is Compound No. 63, 95, 109, 135, 143, 144, 145, 146, or 148. In some embodiments, the compound of the invention is Compound No. 63, 95,109, 135, 145, or 146. In some embodiments, the compound of the invention is Compound No. 143,144, or 148. In some embodiments, the compound of the invention is Example No. 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23,24, 25, 26,27,28,29, 30, 31, 32, 33, 34, 35, 36, 38, 39, 40, 41,42,43, 44, 45,46, 47, 48,49, 50, 50a, 51, or 52 or Compound No. 111, 112, 113, 114, 115, 148 116, 117, 118, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 140, 141,14 2, 143, 144, 145, 147, 149, 150, 151, 152, 153, 154, 155, or 182. In some embodiments, the compound of the invention is Example No. 2, 3, 4, 5, 6, 7 , 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23, 24, 25, 26, 27, 28, 29, 30, 31,32 , 33, 34, 35, 36, 38, 39, 40, 41,42, 43, 44, 45, 46, 47, 48, or 49, or Compound No. 111, 112, 113, 114, 115, 116, 117,118,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138. invention is Compound No. 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152 or 153. In some embodiments, the compound of the invention is Example No. 37 (i.e., Compound No. 74) or Compound No. 119. In some embodiments, the compound of the invention is Example No. 26 (i.e., Compound No. 63), Example No. 45 (i.e., Compound No. 95), Example No. 48 (i.e., Compound No. 109), or Example No. 50 (i.e. Compound No. 146). In some embodiments, the compound of the invention is Example No. 45 (i.e., Compound No. 95) or Example No. 48 (i.e., Compound No. 109). In some embodiments, the compound of the invention is Example No. 26 (i.e., Compound No. 63). In some embodiments, the compound of the invention is Example No. 45 (i.e., Compound No. 95). In some embodiments, the compound of the invention is Example No. 48 (i.e., Compound No. 109). In some embodiments, the compound of the invention is Example No. 50 (i.e., Compound No. 146). Compounds of this invention may contain one or more asymmetric centers (also referred to as a chiral center), such as a chiral carbon or a chiral -SO- moiety. Compounds of this invention comprising one or more chiral centers may be present as racemic mixtures. , diastereomeric mixtures, enantiomerically enriched mixtures, diastereomerically enriched mixtures, or as enantiomerically or diastereomerically pure individual stereoisomers. The stereochemistry of the chiral center present in the compounds of this invention is generally represented in the names of the compounds and / or in the chemical structures illustrated herein. When the stereochemistry of a chiral center present in a compound of this invention, or in any chemical structure illustrated herein, is not specified, the structure is intended to encompass any stereoisomer and all mixtures thereof. Accordingly, the present invention encompasses all isomers of the compounds of any one or more of the Formula (Ij, (lAj, (llj, (lllj, (IVj or (Vj, and salts thereof, either as individual isomers isolated, so as to be substantially free of the other isomer (i.e., pure) or as mixtures (i.e., racemates and racemic mixtures). An individual isomer isolated, so as to be substantially free of the other isomer (i.e., pure) can i CQbzn / zznz / zi / YiAi 149 be isolated such that less than 10%, particularly less than 1%, for example, less than 0.1% of the other isomer is present. Individual stereoisomers of a compound of this invention can be resolved (or mixtures of stereoisomers can be enriched) using methods known to those skilled in the art. For example, such resolution can be carried out (1) by the formation of diastereoisomeric salts, complexes or other derivatives; (2) by selective reaction with a stereoisomer-specific reagent, for example, by enzymatic oxidation or reduction; or (3) by liquid or gas-liquid chromatography in a chiral environment; for example, on a chiral support such as silica with a chiral ligand attached or in the presence of a chiral solvent. It will be appreciated that, when the desired stereoisomer is converted to another chemical entity by one of the separation procedures described above, an additional step is necessary to release the desired form. Alternatively, specific stereoisomers can be synthesized by means of asymmetric synthesis using optically active reagents, substrates, catalysts or solvents, or by converting one enantiomer to the other by asymmetric transformation. The invention also includes various deuterated forms of the compounds of this invention. Each available hydrogen atom bonded to a carbon atom can be independently replaced with a deuterium atom. A person of ordinary skill in the art will know how to synthesize the deuterated forms of the compounds of this invention. For example, α-deuterated amino acids are commercially available, or can be prepared by conventional techniques (see, for example: Elemes, Y. and Ragnarsson, U. J. Chem. Soc, Perkin Trans. 1, 1996, 6, 537 -40). The use of such compounds may allow the preparation of compounds in which the hydrogen atom in a chiral center is replaced with a deuterium atom. It is possible to employ other commercially available deuterated starting materials in the preparation of deuterated analogues of the compounds of this invention (see, for example: methyl-ds-amine available from Aldrich Chemical Co., Milwaukee, WI), or synthesize them using conventional techniques employing deuterated reagents (e.g., by reduction using lithium aluminum deuteride or sodium borodeuteride or by metal-halogen exchange followed by deactivation with D2O or methanol-ds). Suitable pharmaceutically acceptable salts of the compounds of any one or more of Formula (I'), (lAj, (II j, (III j, (IVj or (Vj), may include acid addition salts or base addition salts For more information on suitable pharmaceutically acceptable salts, see Berge et al., J. Pharm. Sci., 66:1-19, (1977) and P. H. Stahl and C. G. Wermuth, Eds., Handbook of Pharmaceutical Salts: Properties, Selection and Use, Weinhem / Zurich: Wiley-VCH / VHCA (2002). Salts of the compounds of any one or more of Formula (I j, (lAj, (llj, (III j, (IVj or (Vj, comprising a basic amine or other basic functional group) may be prepared by any method suitable known in the art, such as treatment of the free base with a suitable organic or inorganic acid. Examples of pharmaceutically acceptable salts formed in this way include acetate, adipate, ascorbate, aspartate, benzenesulfonate, benzoate, camphor, camphorsulfonate (camsylate ), caprate (decanoate), caproate (hexanoate), caprylate (octanoate), carbonate, CQbzn / zznz / zi / YiAi 150 bicarbonate, cinnamate, citrate, cyclamate, dodecyl sulfate (stolate), ethane-1,2-disulfonate (edisylate), ethanesulfonate (esylate), formate, fumarate (hemifumarate, etc.), galactarate (mucate), gentisate (2,5dihydroxybenzoate ), glucoheptonate (gluceptate), gluconate, glucuronate, glutamate, glutarate, glycerophosphorate, glycolate, hippurate, hydrobromide, hydrochloride (dihydrochloride, etc.), iodide, isobutyrate, lactate, lactobionate, laurate, maleate, malate, malonate, mandelate, methanesulfonate (mesylate), naphthalene-1,5-disulfonate (napadisylate), naphthalenesulfonate (napsylate), nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, phosphate (diphosphate, etc.), propionate, pyroglutamate, salicylate, sebacate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate (tosylate), undecylenate, L-hydroxy-2-naphthoate, 2,2dichloroacetate, 2-hydroxyethanesulfonate (isethionate), 2-oxoglutarate, 4-acetamidobenzoate and 4aminosalicylate. Salts of the disclosed compounds comprising a carboxylic acid or other acidic functional group can be prepared by reaction with a suitable base. Said pharmaceutically acceptable salt may be prepared with a base that provides a pharmaceutically acceptable cation, including alkali metal salts (especially sodium and potassium), alkaline earth metal salts (especially calcium and magnesium), aluminum salts and ammonium salts, as well as salts made of physiologically acceptable organic bases such as trimethylamine, triethylamine, morpholine, pyridine, piperidine, picoline, dicyclohexylamine, N, / V-dibenzylethylenediamine, 2hydroxyethylamine, s-(2-hydroxyethyl)amine, tri-(2-hydroxyethyl) ) amine, procaine, dibenzylpiperidine, dehydroabiethylamine, N, / V-basdehydroab¡ethylamine, glucamine, / V-methylglucamine, colidin, choline, quinine, quinoline and basic amino acids, such as lysine and arginine. The invention includes within its scope all possible stoichiometric and non-stoichiometric forms of the salts (e.g., hydrobromide, dibromide, fumarate, hemifumarate, etc.) of the compounds of any one or more of the Formula (I j, (lAj , (II j, (III j, (IV') or (Vj. When a disclosed compound, or its salt, is named or represented by its structure, it should be understood that the compound or salt, including solvates (particularly, hydrates) thereof, may exist in crystalline forms, non-crystalline forms, or a mixture of them. The compound or salt, or solvates (particularly hydrates) thereof, may also exhibit polymorphism (i.e., the ability to appear in different crystalline forms). These different crystal forms are typically known as polymorphs. It is to be understood that the invention includes all polymorphs of any compound of this invention, for example, all polymorphic forms of any compound named or represented by its structure herein, including any salts and / or solvates (particularly, hydrates) thereof. . The polymorphs have the same chemical composition but differ in packing, geometric arrangement, and other properties descriptive of the crystalline solid state. Polymorphs, therefore, can have different physical properties, such as shape, density, hardness, deformability, stability and dissolution properties. Polymorphs typically exhibit different melting points, IR spectra, and X-ray powder diffraction patterns, which can be used for identification. It will be appreciated that it is possible to produce different polymorphs, for example, by changing or adjusting the LCQfrzn / zznz / q / YiAi 151 conditions used in the crystallization / recrystallization of the compound. Polymorphic forms can be characterized and differentiated using a number of standard analytical techniques, including, but not limited to, X-Ray Powder Diffraction (XRPD) patterns, infrared (IR) spectra, Raman spectra, differential calorimetry scanning (DSC, Differential Scanning Calorimetry), thermogravimetric analysis (TGA, Thermogravimetric Analysis) and solid state nuclear magnetic resonance (SSRMN, Solid State Nuclear Magnetic Resonance). The person skilled in the art will appreciate that pharmaceutically acceptable solvates (particularly hydrates) of a compound of any one or more of Formulas (I j, (lAj, (II j, (lllj, (IVj or (Vj, including pharmaceutically acceptable solvates of a pharmaceutically acceptable salt of a compound of any one or more of Formulas (Ij, (lAj, (llj, (lllj, (IVj or (Vj, can be formed when solvent molecules are incorporated into the lattice crystalline during crystallization. Solvates may comprise nonaqueous solvents such as ethanol, or may comprise water as the solvent that is incorporated into the crystal lattice. Solvates in which water is the solvent that is incorporated into the crystal lattice are called typically carbohydrates. The present invention includes within its scope all possible stoichiometric and non-stoichiometric forms of salts and / or hydrates. Salts and solvates (eg, hydrates and salt hydrates) of the compounds of the invention that are suitable for use in medicine are those in which the associated counterion or solvent is pharmaceutically acceptable. Salts having non-pharmaceutically acceptable counterions are within the scope of the present invention; for example, for use as intermediates in the preparation of other compounds of the invention. Typically, a pharmaceutically acceptable salt can be readily prepared using a desired base or acid as appropriate. The resulting salt can be crystallized or precipitated from solution, or formed by means of trituration, and can be recovered by filtration or by evaporation of the solvent. As the compounds of this invention are intended for use in pharmaceutical compositions, it will be readily understood that each of them is preferably provided in substantially pure form, for example, at least 60% pure, more suitably at least 75% pure, and preferably at less 85% pure, especially at least 98% pure (% weight by weight basis). Impure preparations of the compounds can be used to prepare the purer forms used in pharmaceutical compositions. The invention encompasses all prodrugs of the compounds of this invention, which, upon administration to the recipient, are capable of providing (directly or indirectly) a compound of this invention, or an active metabolite or residue thereof. Said derivatives are recognizable by experts in the field, without excessive experimentation. However, reference is made to the teaching of Burger's Medicinal Chemistry and Drug Discovery, 5th Edition, Vol 1: Principles and Practice, which is incorporated herein by reference to the extent that it teaches such derivatives. I CQb7(3 / 77(37 / 3 / ΥΙΛΙ 152 It is further to be understood that the present invention includes within its scope all tautomeric or isomeric forms of any free base form of the compounds of this invention, as well as all possible forms of stoichiometric and non-stoichiometric salts. The compounds of the invention are useful in the treatment or prevention of diseases and disorders in which modulation of STING is beneficial. Such STING-mediated diseases and disorders include inflammation, allergic and autoimmune diseases, infectious diseases, cancer, and precancerous syndromes. The compounds of the invention are also useful as an immunogenic composition or vaccine adjuvant. Accordingly, this invention is directed to a method of modulating STING comprising contacting a cell with a compound of the invention. Methods of use In some embodiments, this invention provides a compound for use in a STING antibody-agonist candidate. In some embodiments, the STING antibody-agonist conjugate contains a linker. The invention further provides an antibody-STING agonist conjugate for use in therapy. The invention further provides the use of an antibody-STING agonist conjugate indicated above for the manufacture of a medicament. In some embodiments, the STING agonist has, or is modified to include, a group reactive with a conjugation site on an antibody. One aspect of the invention provides methods of treating or preventing STING-mediated diseases and disorders, in which STING agonism is beneficial. Exemplary diseases / disorders include, but are not limited to: cancer, infectious diseases (e.g., HIV, HBV, HCV, HPV, and influenza), vaccine adjuvant. In some embodiments, the STING pathway can induce antitumor immunity by upregulating interferon (IFN)-stimulated genes (ISGs) and IFNp in many cell types within tumors in response to cytosolic nucleic acids. agonists. In some embodiments, this invention provides a compound of the invention for use in therapy. This invention also provides a compound of any one or more of Formulas (Ij, (lAj, (llj, (lllj, (IVj, or (Vj), or a pharmaceutically acceptable salt thereof, for use in therapy. This invention particularly provides a compound of any one or more of Formulas (I j, (lAj, (llj, (lllj, (IVj, or (Vj), or a pharmaceutically acceptable salt thereof, for use in the treatment of a disease or disorder mediated by STING. This invention also provides a compound of any one or more of Formulas (I j, (IA j, (llj, (lllj, (IVj, or (Vj), or a pharmaceutically acceptable salt thereof, for use as an adjuvant of Therefore, also provided is an immunogenic or vaccine adjuvant composition comprising a compound of any one or more of Formulas (Ij, (IAj, (llj, (lllj, (IVj, or (Vj, or a salt pharmaceutically acceptable thereof. LCQfrzn / zznz / q / viAi 153 In another embodiment of the invention, a composition is provided comprising a compound of any one or more of the Formulas (Ij, (lAj, (llj, (IIIj, (IVj, or (Vj, or a pharmaceutically acceptable salt of the same, and one or more immunostimulating agents. In some embodiments, this invention provides a compound of the invention for use in the treatment of a STING-mediated disease or disorder and / or for use as an immunogenic composition or a vaccine adjuvant. In some embodiments, this invention particularly provides a compound of any one or more of Formulas (Ij, (lAj, (llj, (IIIj, (IVj, or (Vj), or a pharmaceutically acceptable salt thereof, for use in alleviating injury or organ damage as a result of a STING-mediated disease or disorder. The invention further provides the use of a compound of the invention in the manufacture of a medicament for the treatment of a STING-mediated disease or disorder. The invention further provides the use of a compound of any one or more of the Formulas (Ij, (lAj, (llj, (IIIj, (IVj, or (Vj), or a salt thereof, particularly a pharmaceutically acceptable salt of the themselves, in the manufacture of a medicament for the treatment of a STING-mediated disease or disorder; for example, the diseases or disorders mentioned herein. The invention further provides the use of a compound of any one or more of the Formulas (Ij, (lAj, (llj, (lllj, (IVj, or (Vj), or a salt thereof, particularly a pharmaceutically acceptable salt of the themselves, in the manufacture of a vaccine. Furthermore, the use of a compound of any one or more of the Formulas (Ij, (lAj, (llj, (lllj, (IVj, or (Vj, or a pharmaceutically acceptable salt thereof, for the manufacture of an immunogenic composition or a vaccine composition comprising an antigen or antigenic composition, for the treatment or prevention of diseases. In some embodiments, the invention is directed to a method of treating a STING-mediated disease or disorder comprising administering a therapeutically effective amount of a compound of any one or more of Formulas (I j, (lAj, (llj, (lllj, (IVj, or (Vj, or a salt, particularly a pharmaceutically acceptable salt thereof, to a human in need. In some embodiments, the invention is directed to a method of treating or preventing diseases, comprising administering to a human subject suffering from or susceptible to diseases, an immunogenic composition or a vaccine composition comprising an antigen or antigenic composition. and a compound of any one or more of the Formulas (Ij, (lAj, (llj, (lllj, (IVj, or (Vj), or a pharmaceutically acceptable salt thereof. In some embodiments, this invention is directed to a compound of any one or more of Formulas (Ij, (lAj, (llj, (lllj, (IVj, or (Vj), or a pharmaceutically acceptable salt thereof for use in the treatment of inflammation, an autoimmune disease, an allergic disease, an infectious disease, an HIV infection, an AIDS infection, an HCV infection, influenza, or a human papillomavirus (HPV) infection. In another aspect , a method is provided to treat inflammation, an autoimmune disease, an allergic disease, an infectious disease, an HIV infection, an AIDS infection, an HCV infection, influenza, or a human papillomavirus (HPV) infection. , which includes administering to a human who needs it a quantity LCQfrzn / zznz / q / YiAi 154 therapeutically effective of a compound of any one or more of Formulas (I j, (lAj, (II j, (III j, (IVj, or (Vj, or a pharmaceutically acceptable salt thereof. In another aspect, provided a compound of any one or more of Formulas (Ij, (lAj, (llj, (lllj, (IVj, or (Vj), or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for the treatment of inflammation, an autoimmune disease, an allergic disease, an infectious disease, an HIV infection, an AIDS infection, an HCV infection, influenza, or a human papillomavirus (HPV) infection. As used herein, the terms cancer, neoplasm, and tumor are used interchangeably and, whether singular or plural, refer to cells that have undergone a malignant transformation that renders them pathological to the host organism. Primary cancer cells can be easily distinguished from non-cancerous cells using well-established techniques; particularly, histological examination. The definition of a cancer cell, as used herein, includes not only a primary cancer cell, but any cell derived from a cancer cell ancestor. This includes metastatic cancer cells and in vitro cultures and cell lines derived from cancer cells. When referring to a type of cancer that typically manifests as a solid tumor, a clinically detectable tumor is one that can be detected based on tumor mass; for example, by procedures such as computed tomography (CT), magnetic resonance imaging (MRI), cancer in a sample obtainable from a patient. The tumors may be a hematopoietic (or hematologic or blood-related) cancer; for example, types of cancer derived from blood or immune cells, which may be called liquid tumors. Specific examples of clinical conditions based on hematological tumors include leukemias such as chronic myelocytic leukemia, acute myelocytic leukemia, chronic lymphocytic leukemia, and acute lymphocytic leukemia; plasma cell malignancies such as multiple myeloma, MGUS, and Waldenstrom macroglobulinemia; lymphomas such as non-Hodgkin lymphoma, Hodgkin lymphoma; and the like. The cancer can be any cancer in which an abnormal number of blast cells or unwanted cell proliferation is present or is diagnosed as a hematological cancer, including lymphoid and myeloid malignancies. Myeloid malignancies include, but are not limited to, acute myeloid (or myelocytic or myelogenous or myeloblastic) leukemia (undifferentiated or differentiated), acute promyeloid (or promyelocytic or promyelogenic or promyeloblastic) leukemia, acute myelomonocytic (or myelomonoblastic) leukemia, or acute monocytic (or monoblastic), erythroleukemia and megakaryocyte (or megakaryoblastic) leukemia. These leukemias may be collectively referred to as acute myeloid (or myelocytic or myelogenous) leukemia (AML). Myeloid neoplasms also include myeloproliferative disorders (MPD), including, but not limited to, chronic myelogenous (or myeloid) leukemia (CML), chronic myelomonocytic leukemia (CMML), essential thrombocythemia ( or thrombocytosis) and polycythemia vera (PCV). Myeloid neoplasms also include myelodysplasia (or myelodysplastic syndrome (MDS). LCQfrzn / zznz / q / YiAi 155 Syndrome), which may be called Refractory Anemia (RA), Refractory Anemia with Excess Blasts (RAEB), and Refractory Anemia with Excess Blasts in Transformation (RAEBT); as well as myelofibrosis (MFS) with or without angiogenic myeloid metaplasia. Hematopoietic cancers also include lymphoid neoplasms, which may involve lymph nodes, spleen, bone marrow, peripheral blood, and / or extranidal sites. Lymphoid cancers include B-cell neoplasms, including, but not limited to, B-cell Non-Hodgkin's Lymphoma (B-NHL). B-NHLs can be indolent (or low grade), intermediate grade (or aggressive), or high grade (very aggressive). Indolent B-cell lymphomas include follicular lymphoma (FL); small lymphocytic lymphoma (SLL); marginal zone lymphoma (MZL) including nodal MZL, extranidal MZL, splenic MZL, and splenic MZL with villous lymphocytes; lymphoplasmacytic lymphoma (LPL); and mucosa-associated lymphoid tissue lymphoma (MALT, MucosaAssociated-Lymphoid Tissue, or extranidal marginal zone). Intermediate-grade B-NHL includes mantle cell lymphoma (MCL) with or without leukemic involvement, diffuse large cell lymphoma (DLBCL), follicular large cell lymphoma (or grade 3 or grade 3B) and primary mediastinal lymphoma (PML). High-grade B-NHL includes Burkitt's lymphoma (BL), Burkitt-like lymphoma, small non-cleaved cell lymphoma (SNCCL), and lymphoblastic lymphoma. Other BNHL include immunoblastic lymphoma (or immunocytoma), primary effusion lymphoma, HIV-associated (or AIDS-related) lymphomas, and post-transplant lymphoproliferative disorder (PTLD). B-cell malignancies also include, but are not limited to, chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), Waldenstrom's macroglobulinemia (WM), hairy cell leukemia (HCL). , Hairy Cell Leukemia), large granular lymphocyte (LGL) leukemia, acute lymphoid (or lymphocytic or lymphoblastic) leukemia, and Castleman disease. NHL may also include T-Cell non-Hodgkin's Lymphoma (TNHL), including, but not limited to, T-cell non-Hodgkin's lymphoma not otherwise specified (NOS), Peripheral T-cell Lymphoma (PTCL), Anaplastic Large Cell Lymphoma (ALCL), Angioimmunoblastic Lymphoid Disorder (AILD), Nasal T-cell / Natural Killer (NK) cell lymphoma ), gamma / delta lymphoma, cutaneous T-cell lymphoma, mycosis fungoides, and Sezary syndrome. Hematopoietic cancers also include Hodgkin lymphoma (or disease), including classical Hodgkin lymphoma, nodular sclerosing Hodgkin lymphoma, mixed cellularity Hodgkin lymphoma, lymphocyte predominant (LP) Hodgkin lymphoma, lymphocyte predominant (LP) Hodgkin lymphoma. Nodular LP, and lymphocyte-depleted Hodgkin lymphoma. Hematopoietic cancers also include plasma cell cancers or diseases such as multiple myeloma (MM), including MM LCQfrzn / zznz / q / YiAi 156 latent, monoclonal gammopathy of undetermined (or unknown or uncertain) significance (MGUS), plasmacytoma, (osseous, extramedullary lymphoma, lymphoplasmacytic lymphoma (LPL), Waldenstrom's macroglobulinemia, plasma cell leukemia, and amyloidosis (AL) primary. Hematopoietic cancers may also include other cancers of additional hematopoietic cells, including polymorphonuclear leukocytes (or neutrophils), basophils, eosinophils, dendritic cells, platelets, erythrocytes, and natural killing cells. Tissues that include hematopoietic cells called Herein, hematopoietic cell tissues include bone marrow; peripheral blood; thymus; and peripheral lymphoid tissues, such as spleen, lymph nodes, mucosa-associated lymphoid tissues (such as intestine-associated lymphoid tissues), tonsils, Peyer's patches, and appendix, and lymphoid tissues associated with other mucosa, for example, the bronchial linings. In some embodiments, this invention is directed to a compound of any one or more of Formulas (I j, (lAj, (II j, (lllj, (IV j or (Vj, or a pharmaceutically acceptable salt thereof, for its use in the treatment of cancer and pre-cancerous syndromes. In another aspect, a method is provided for treating cancer and pre-cancerous syndromes, which comprises administering to a human in need thereof a therapeutically effective amount of a compound of one or more any of Formulas (I j, (lAj, (llj, (lllj, (IV j or (Vj), or a pharmaceutically acceptable salt thereof. In another aspect, a compound of any one or more of Formulas (I j , (IAj, (II j, (lllj, (IV j or (Vj, or a pharmaceutically acceptable salt thereof, for use in the manufacture of a medicament for the treatment of cancer and pre-cancerous syndromes. The compounds of this invention can be used to treat inflammation of any tissue and organ in the body, including musculoskeletal inflammation, vascular inflammation, neural inflammation, inflammation of the digestive system, ocular inflammation, inflammation of the reproductive system, and other types of inflammation. Examples of diseases and cancer conditions in which the compounds of this invention may have potentially beneficial antitumor effects include, but are not limited to: cancer of the lung, bone, pancreas, skin, head, neck, uterus, ovaries, stomach, colon, breast, esophagus, small intestine, intestine, endocrine system, thyroid gland, parathyroid gland, adrenal gland, urethra, prostate, penis, testicles, urethra, bladder, kidney or liver; rectal cancer; cancer of the anal region; fallopian tube, endometrial, cervix, vaginal, vulvar, pelvic, renal, renal cell carcinomas; soft tissue sarcoma; myxoma; rhabdomyoma; fibroma; lipoma; teratoma; cholangiocarcinoma; hepatoblastoma; angiosarcoma; hemangioma; hepatoma; fibrosarcoma; chondrosarcoma; myeloma; chronic or acute leukemia; lymphocytic lymphomas; primary CNS lymphoma; CNS neoplasms; spinal axis tumors; squamous cell carcinomas; synovial sarcoma; malignant pleural mesotheliomas; brainstem glioma; pituitary adenoma; bronchial adenoma; chondromatous hamartoma; mesothelioma; Hodgkin's disease, or a combination of one or more of the above cancers. LCQfrzn / zznz / q / viAi 157 Suitably, the present invention relates to a method of treating or alleviating the severity of cancer. In some embodiments, the compounds of the present invention can be used to treat sarcoma, breast cancer, colorectal cancer, gastroesophageal cancer, melanoma, non-small cell lung cancer (NSCLC), carcinoma Clear Cell Renal Carcinoma (RCC), Lymphomas, Squamous Cell Carcinoma of the Head and Neck (SCCHN), Hepatocellular Carcinoma (HCC), and Non-Hodgkin Lymphoma (NHL). Non-Hodgkin Lymphoma). Suitably, the present invention relates to a method of treating or alleviating the severity of pre-cancerous syndromes in a mammal, including a human. In one aspect, the human has a solid tumor. In one aspect, the tumor is selected from head and neck cancer, gastric cancer, melanoma, renal cell carcinoma (RCC), esophageal cancer, non-small cell lung carcinoma, prostate cancer, colorectal cancer, ovarian cancer. and pancreatic cancer. In some embodiments, the human has a liquid tumor such as diffuse large B cell lymphoma (DLBCL), multiple myeloma, chronic lymphoblastic leukemia (CLL), follicular lymphoma, acute myeloid leukemia, and chronic myelogenous leukemia. In some embodiments, the compounds of the present invention may be useful for the treatment of skin cancer (e.g., non-melanoma skin cancer, squamous cell carcinoma, basal cell carcinoma) or actinic keratosis. In addition to a field effect in eliminating superficial skin cancers, the compounds of the present invention can prevent the development of subsequent skin cancers and premalignant actinic keratosis in treated patients. The compounds of the present invention may also be useful in the treatment of one or more diseases affecting mammals, which are characterized by cell proliferation in the area of ​​disorders associated with neovascularization and / or vascular permeability, fibrotic disorders and metabolic disorders. . The compounds of this invention can be used to treat neurodegenerative diseases. Exemplary neurodegenerative diseases include, but are not limited to, multiple sclerosis, Huntington's disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS). The compounds of this invention can be used to treat an infectious disease, which is any disease instigated or coincident with an infection of a pathogen, derived from bacteria, derived from DNA virus families or RNA virus families. The compounds of this invention can be used alone or in combination with other therapeutic agents. As immune response modulators, the compounds of this invention can also be used in monotherapy or in combination with another therapeutic agent in the treatment of diseases and conditions in which modulation of STING is beneficial. Combination therapies according to the present invention therefore comprise the administration of a compound of any one or more of the Formulas (Ij, (lAj, (II j, (lllj, (IVj, or (Vj, or a salt pharmaceutically acceptable thereof, and at least one other therapeutically active agent. In some embodiments, the i CQbzn / zznz / ci / YiAi 158 combination therapies according to the present invention comprise the administration of at least one compound of any one or more of Formulas (I'), (ΙΑ'), (II'), (III'), (IV'), or (V), or a pharmaceutically acceptable salt thereof, and at least one other therapeutic agent. The compound(s) of any one or more of Formulas (I'), (ΙΑ'), (II'), (III'), (IV'), or (V'), and pharmaceutically acceptable salts thereof , and the other distinct therapeutic agent(s) may be administered together in a single pharmaceutical composition or separately and, when administered separately, this may occur simultaneously or sequentially in any order. The amounts of the compound or compounds of any one or more of Formulas (Γ), (ΙΑ'), (II'), (ΙΙΓ), (IV'), or (V'), and pharmaceutically acceptable salts of the themselves, and the other therapeutic agent(s) and relative administration times will be selected to achieve the desired combined therapeutic effect. Therefore, in another aspect, there is provided a composition comprising a compound of any one or more of Formulas (I'), (ΙΑ'), (II'), (III'), (IV'), or (V'), or a pharmaceutically acceptable salt thereof, together with one or more other therapeutic agents. Compounds of any one or more of Formulas (I'), (ΙΑ'), (II'), (ΙΙΓ), (IV'), or (V'), and pharmaceutically acceptable salts thereof, may be used in combination with one or more other therapeutic agents that may be useful in the prevention or treatment of allergic diseases, inflammatory diseases or autoimmune diseases, for example; immunotherapy with antigens, antihistamines, spheroids, nonsteroidal anti-inflammatory drugs (NSAIDs), bronchodilators, methotrexate, leukotriene modulators, monoclonal antibody therapy, receptor therapies, or non-specific antigen immunotherapies. Compounds of any one or more of Formulas (I'), (ΙΑ'), (II'), (ΙΙΓ), (IV), or (V), and pharmaceutically acceptable salts thereof, may be used in combination with radiotherapy and / or surgery and / or at least one other therapeutic agent that may be useful in the treatment of cancer and precancerous syndromes. Any antineoplastic, antimicrotubular, antimitotic agent, hormone, hormone analog, signal transduction pathway inhibitor, protein tyrosine kinase, or antiangiogenic therapeutic agent may be used. Agents used in immunotherapeutic regimens, therapeutic agents used in proapoptotic regimens, or cell cycle signaling inhibitors may also be useful in combination with the compounds of any one or more of Formulas (I'), (ΙΑ'), (II '), (III'), (IV), or (V). In some embodiments, the combination of the present invention comprises a compound of any one or more of Formulas (I'), (ΙΑ'), (II'), (III'), (IV), or (Vj , or a salt, particularly a pharmaceutically acceptable salt thereof, and at least one antineoplastic, antimicrotubular agent, antimitotic agent, hormone, hormonal analogues, signal transduction pathway inhibitor, protein tyrosine kinase, or antiangiogenic therapeutic agent, or a combination thereof. I CQb7n / 77n7 / =l / YIAI 159 Additional examples of other therapeutic agents (e.g., antineoplastic agent) for use in combination, or co-administered with a compound of any one or more of Formulas (I'), (ΙΑ'), (II'), ( III'), (IV'), or (V'), or a pharmaceutically acceptable salt thereof, are immunomodulators. As used herein, immunomodulators refer to any substance, including monoclonal antibodies, that affects the immune system. Immunomodulators can be used as antineoplastic agents for cancer treatment. For example, immunomodulators include, but are not limited to, anti-CTLA-4 antibodies such as ipilimumab (YERVOY) and anti-PD-1 antibodies (Opdivo / nivolumab and Keytruda / pembrolizumab). Other immunomodulators include, but are not limited to, ICOS antibodies, OX-40 antibodies, PD...

Claims

1. A compound of Formula (lAj R14 I CQb7n / 77n7 / =l / Yl· or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Wi, Xi, Yi, Zi, W2, X2, Y2, and Z2 are each independently O, S, C, or N; Xa and X4 are each independently S or NRf; Xs is N or CRA2; Xe is N or CR1; X9 is N or CR4; rys are each independently O or 1; p is 1 or 2; the total of rys is 1 or 2; raí and ra2 are each independently H, halogen, amino, amino(Ci-4 alkyl)-, hydroxyl, OP(O)(OH)2i -OP(O)(R'R)2, -N(Re)(R<), -CO2Rf, -NÍRjCORL -N(P3)802(0ι-43^υίΙ)-N(P®)(P'), N(R9)CO(Ci-4 alkyl)-N(Rh)(Rf), optionally substituted (C1-6 alkyl), optionally substituted (C1-6 alkyl)oxy, optionally substituted (C1-6 alkyl)amino, and optionally substituted (Ci s alkyl)(Ci-4 alkyl)amino, wherein the (C1-6 alkyl) of said optionally substituted (C1-6 alkyl), optionally substituted (Ci-β alkyl)oxy,(C1-6 alkyl)amino- optionally substituted and (Ove alkyl)(C1-4 alkyl)amino- optionally substituted is optionally substituted with 1-4 substituents, each independently selected from hydroxyl, -OP(O)(OH)2, -OP(O)(R'R)2, C1-4 alkoxy-, -N(Re)(R*), -CC^CRj, -CON^XRj, optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, hydroxyl, -OP(O)(OH)2, -OP(O)(RIR)2, amino, (C1-6 alkyl)amino-, (C1-6 alkyl)(C1-6 alkyl)amino, -(C1-6 alkyl)NH2, halo(C1-6 alkyl), hydroxy-(Ci-4 alkyl)-, -(C1-4 alkyl)-OP(O)(OH)2, -(C1-4 alkyl)-O 246 P(O)(R'R)2, halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-O-P(O)(OH)2, -(C2-4 alkoxy)-OP(O)(R'R)2, -C1-4 alkyl-(Ci-4 alkoxy), and C1-4 alkoxy-(Ci-4 alkoxy)-; when r is 0, RB1 and RB2 are,each independently, H, Ci-e optionally substituted alkyl, halo(Ci-s alkyl), C2-6 optionally substituted alkenyl, C2-6 optionally substituted alkynyl, C3-6 optionally substituted cycloalkyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl, wherein said Oe optionally substituted alkyl, C2-6 optionally substituted alkenyl, C2-6 optionally substituted alkynyl, C3-6 optionally substituted cycloalkyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted phenyl, optionally substituted 5-6 membered heteroaryl, or optionally substituted 9-10 membered heteroaryl is optionally substituted with 1-4 substituents each independently selected from halogen, nitro, -Rc, OH, -OP(O)(OH)2, -OP(O)(R'R)2 -ORc, -NH2, -NRcRc, -NRcRd, -OCORC, -CO2H,-CO2RC, -SORC, -SO2RC, -CONHa, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and -NRdSO2Rc; where s is 0, RC1 is absent, or is H, halogen, or C1-4 alkyl and RC2 is absent or is optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl group is optionally substituted with a substituent selected from -ORC, -NRcRd, -CO2RC, -CONRcRd, SO2NRcRd, and -OCONRcRd; when r is 1, RB1 and RB2 are, each independently, -CH2-, and B, taken together with RB1 and RB2, forms a linking group, wherein B is a linker or B is -halo(Ci-io alkyl)-, -C1-10 optionally substituted alkyl, -C2-10 optionally substituted alkenyl-, -C2-10 optionally substituted alkynyl-, -C1-6 optionally substituted alkyl-O-Ci-6 alkyl, -Ci-β alkyl-NRa-Ci-6 alkyl-, optionally substituted C3-6 optionally substituted cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl,optionally substituted 5-6 membered heteroaryl, -C1-4 alkyl(C3 e cycloalkyl)-C1-4 alkyl- optionally substituted, -C1-4 alkyl-phenyl-C1-4 alkyl- optionally substituted, -C1-4 alkyl-(4-6 membered heterocycloalkyl)-C1-4 alkyl- optionally substituted, or -C1-4 alkyl-(5-6 membered heteroaryl)-C1-4 alkyl- optionally substituted, wherein the alkyl moiety of said optionally substituted -C1-10 alkyl- optionally substituted, -C2-10 alkenyl- optionally substituted, -C2-10 alkynyl- optionally substituted, -C1-6 alkyl-O-C1-6 alkyl- optionally substituted, -C1-6 alkyl-NRa-C1-6 alkyl- optionally substituted, -C14 optionally substituted alkyl-(C3-6 cycloalkyl)-Ci-4 alkyl, optionally substituted -C1-4 alkyl-phenyl-Ci-4 alkyl, optionally substituted C1-4 alkyl-(4-6 membered heterocycloalkyl)-Ci-4 alkyl, or optionally substituted -C1-4 alkyl(5-6 membered heteroaryl-Ci-4 alkyl) is optionally substituted with 1 or 2 substituents,each independently selected from halogen, halo(Ci-4 alkyl), -OH, -OP(O)(OH)2, -OP(O)(R'R)2, -ORc, -NH2, -NRcRd, -OCORC, -CO2H, -CO2RC, -SORC, -SO2RC, -CONH2, CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and NRdSO2Rc, and the remainder C3-6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl of said C3-6 cycloalkyl optionally substituted, phenyl optionally substituted, 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, optionally substituted -C1-4 alkyl(C3-6 cycloalkyl)-C1-4 alkyl, optionally substituted -C1-4 alkylphenyl-C1-4 alkyl, optionally substituted -C1-4 alkyl-(4-6 membered heterocycloalkyl)-C1-4 alkyl, or optionally substituted -C1-4 alkyl-(5-6 membered heteroaryl)-C1-4 alkyl is optionally substituted with 1-4 substituents,each independently selected from halogen, hydroxyl, -OP(O)(OH)2, -O-PIOXOR'R^ amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(C1-4 alkyl)amino-, C1-4 alkyl, halo(C1-4 alkyl), halo(C1-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-O-P(O)(OH)2, -(C2-4 alkoxy)-OP(O)(R'R)2, and C1-4 alkoxy-(C1-4 alkoxy)-; when s is 1, W1 and Z2 are, each independently, C or N, RC1 and RC2 are, each independently, -CH2-, and D taken together with RC1 and RC2, forms a linking group, wherein D is halo(Ci-i2 alkyl)-, -C1-12 alkyl- optionally substituted, -C2-12 alkenyl- optionally substituted, -C2-12 alkynyl- optionally substituted, -C1-6 alkyl-O-Ci-6 alkyl- optionally substituted, -C1-6 alkyl-NRa-Ci-6 alkyl- optionally substituted, -C1-6 alkyl-(C3-6 cycloalkyl)-Ci-6 alkyl- optionally substituted, -Ci-e alkyl-phenyl-Ci-6 alkyl- optionally substituted, -Ci-β alkyl-(4-6 membered heterocycloalkyl)-Ci-6 alkyl- optionally substituted,or optionally substituted -C1-6 alkyl-(5-6 membered heteroaryl)-Ci-6 alkyl, wherein the alkyl moiety of said optionally substituted -C1-12 alkyl, optionally substituted -C1-6 alkenyl, optionally substituted -C2-12 alkynyl, optionally substituted -C1-6 alkyl-O-Ci-6 alkyl, optionally substituted -Ci-β alkyl-NRa-Ci-6 alkyl, optionally substituted -C1-6 alkyl-(C3-6 cycloalkyl)-Ci-6 alkyl, optionally substituted -Ci-β alkylphenyl-Ci-s alkyl, optionally substituted C1-6 alkyl-(4-6 membered heterocycloalkyl)-Ci-6 alkyl, or optionally substituted -Ci-β alkyl(5-6 membered heteroaryl optionally substituted Ci-6 alkyl members is optionally substituted with 1 or 2 substituents, each independently selected from halogen, halo(Ci-4 alkyl), -OH, -OP(O)(OH)2, -O-PIOXR'RHX, -ORc, -NH2, -NRcRd, -OCORC, -CO2H, -CO2R®, -SORC, -SO2RC, -CONH2, CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, and NRdSO2Rc,and the remaining C3-6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, or 5-6 membered heteroaryl of said optionally substituted -C1-6 alkyl-(C3-6 cycloalkyl)-C1-6 alkyl, optionally substituted -C1-6 alkyl-phenyl-C1-6 alkyl, optionally substituted -C1-6 alkyl-(4-6 membered heterocycloalkyl)-C1-6 alkyl, or optionally substituted -C1-6 alkyl-(5-6 membered heteroaryl)-C1-6 alkyl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -OP(O)(OH)2, OP(O)(R'R)2, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(C1-4 alkyl)amino, C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-OP(O)(OH)2, -(C^alkoxO-O-PÍOXR'R^ and C1-4 alkoxy-(Ci-4 alkoxy)-; R3 and R5 are, each independently, -CON(Rd)(Rj, -OHΗζN^χΡ1), -N(Rd)(R*), -N(Rd)CO(R<), -CH2N(Rd)CO(Rf), or I CQb7n / 77n7 / =l / YIAI 248 one of R3 and R5 is -CONCR^ÍRj, -C^N^XRf), -N(Rd)(Rf), -N(Rd)CO(R*),or -CH2N(Rd)CO(R*), and the other of R3 and R5 is H, COOH, or -CO2RC; R4 and Rs are each independently selected from H, halogen, halo(Ci-6 alkyl), halo(Ci-6 alkoxy)-, hydroxyl, -OP(O)(OH)2, OP(O)(RR)2, -NH2, -NRCRC, -NRcRd, -CORC, -CO2RC, N(Rd)CORc, -N(Rd)SOzRc, -N(Rs)SO2(Ci-2 alkyl^-NCR^R1), -N(R9)CO(Ci-2 alkyl)-N(Rh)(Rf), optionally substituted (Ci-6 alkyl), optionally substituted (Ci alkyl)oxy-, optionally substituted (Ci alkyl)amino-, and optionally substituted (Ci alkyl)(Ci 4 alkyl)amino-, wherein the (Oe alkyl) of said optionally substituted (Cve alkyl, (Cve alkyl)oxy optionally substituted, (Oe alkyl)amino optionally substituted and (O-6 alkyl)(Ci-4 alkyl)amino optionally substituted is optionally substituted with 1-4 substituents, each independently selected from -OH, -OP(O)(OH)2, -OP(O)(RIR)2, -ORC, -NH2, -NRcRc, -NRcRd, -CO2H, -CO2Rc, -OCORc, -CO2H, -CO2Rc, -SORc, -SO2Rc -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd,OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, -NRdSO2Rc, optionally substituted phenyl, optionally substituted 5-6 membered heterocycloalkyl, and optionally substituted 5-6 membered heteroaryl group, wherein said optionally substituted phenyl, 5-6 membered heterocycloalkyl, or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -OP(O)(OH)2, -OP(O)(R'R)2, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(C1-4 alkyl)amino-, C1-4 alkyl, halo(C1-4 alkyl), hydroxy-(C1-4 alkyl)-, -(C1-4 alkyl)-OP(O)(OH)2, -(C1-4 alkyl)-OP(O)(R'R)2, halo(C1-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alCOXY)-OP(O)(OH)2, -(C2-4 alkoxy)-OP(O)(R'R)2, C1-4 alkoxy-(C1-4 alkoxy)-, -CORd, -CONCR^CR1), and -CO2Rd, R14 is absent, or is H, halogen, or C1-4 alkyl optionally substituted,wherein said C1-4 optionally substituted alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; R16 is absent, or is H, halogen, or C1-4 alkyl; R15 and R17, each independently, are absent, or are H, cyclopropyl, halogen, or C1-4 optionally substituted alkyl, wherein said C14 optionally substituted alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; or R15 and R17, taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; or R16 and taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; R18 and R19, each independently, are absent, or are H, halogen, C1-4 optionally substituted alkyl,wherein said C1-4 optionally substituted alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; or R17 and R18 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; Ra is H, -Rc, -CORC, -CO2H, -CO2RC, -SORC, -SO2RC, -CONH2, -CONRcRd, -SO2NH2, -CH2-CO2RC, or -SO2NRcRd; I CQb7n / 77n7 / =l / YIAI 249 each Rb is independently Ci-4 alkyl, halo(Ci-4 alkyl), -(Ci-4 alkyl)-OH, -(Ci-4 alkyl)-OP(O)(OH)2, -(Ci-4 alkylj-O-PÍOjíR'R1^, -(Ci-4 alkyl)-O-(Ci-4 alkyl), -(Ci-4 alkyl)-N(Re)(Rf), -(Ci-4 alkyl)-OCO(Ci-4 alkyl), or -(Ci-4 alkyl)-CO-O-(Ci-4 alkyl); each Rc is independently H, Ci-4 alkyl, halo(Ci-4 alkyl), -(Ci-4 alkyl)-OH, -(Ci-4 alkyl)-OP(O)(OH)2, -(Ci-4 alkyl)-OP(O)(R'R)2, -(Ci-4 alkyl)-O-(Ci-4 alkyl), -(Ci-4 alkyl)-N(R®)(Rf), -(Ci-4 alkyl)-OCO(Ci-4 alkyl), -(Ci-4 alkyl)-CO-O-(Ci-4 alkyl),optionally substituted C3-6 cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, optionally substituted 9-10 membered heteroaryl, -C3-4 optionally substituted alkylphenyl, -C3-4 optionally substituted 4-6 membered alkylheterocycloalkyl, -C3-4 optionally substituted 5-6 membered alkylheteroaryl, or -C3-4 optionally substituted 9-10 membered alkylheteroaryl, wherein the C3-6 cycloalkyl, phenyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl or 9-10 membered heteroaryl residue of said optionally substituted C3-6 cycloalkyl, optionally substituted phenyl, optionally substituted heterocycloalkyl of 4-6 member optionally substituted, 5-6 member optionally substituted heteroaryl, 9-10 member optionally substituted heteroaryl,Optionally substituted -Ci-4 alkyl-C36 cycloalkyl, optionally substituted -Ci-4 alkyl-phenyl, optionally substituted 4-6 membered -Ci-4 alkylheterocycloalkyl, optionally substituted 5-6 membered -Ci-4 alkyl-heteroaryl, or optionally substituted 9-10 membered -Ci-4 alkyl-heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -OP(O)(OH)2, -OP(O)(RIR)2, amino, (Ci-4 alkyl)amino-, (Ci-4 alkyl)(Ci-4 alkyl)amino, Ci-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, Ci-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-OP(O)(OH)2, -(C2-4 alkoxy)-OP(O)(R'R)2, Ci-4 alkoxy-(Ci-4 alkoxy)-, -CORd, -CONtR^R1), and -CO2Rd; each Rd is independently H, hydroxyl, or Ci-4 alkyl; each R® is independently H, (Ci-4 alkyl), -CO(Ci-4 alkyl), -OCO(Ci-4 alkyl), -CO2(Ci-4 alkyl), -(C1-4 alkyl)amino, -(C1-4 alkyl)-Ci 4 alkoxy,-CO-(optionally substituted 5-6 member heterocycloalkyl), -CO-(Ci 4 alkyl)-(optionally substituted 5-6 member heterocycloalkyl), -CO-(optionally substituted 5-6 member heteroaryl), -CO-(Ci-4 alkyl)-(optionally substituted 5-6 member heteroaryl), wherein the optionally substituted 5-6 member heterocycloalkyl or optionally substituted 5-6 member heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -OP(O)(OH)2, -OP(O)(R'R)2, amino, (Ci-4 alkyl)amino-, (Ci-4 alkyl)(Ci-4 alkyl)amino-, Ci-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, Ci-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy) OP(O)(OH)2, -(C2-4 alkoxy)-O-P(O)(R'R)2, Ci-4 alkoxy-(Ci-4 alkoxy)-, CORd, -CONÍRRÍRR and -CO2Rd; each Rf is independently H, hydroxyl, or (Ci-4 alkyl); Rg and Rh are each independently H or (Ci-4 alkyl) or Ra and Rh,taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; and each R1 and R are independently (C1-6 alkyl)oxy-; I CQb76 / 7767 / 3 / YILI 250 provided that at least one of (i), (ii), or (iii) applies: (i) when s is 0, r is 1, (a) Zi, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S or X9 is N; or (i) when s is 0, r is 1, (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C, then R14 is a C1-4 halogen-substituted alkyl, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd where Rc is H; or (iii) when s is 0,r is 1, (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of Xs, Xs, and Xg is N and RA1 or RA2 is halogen, hydroxyl, (Os alkyl) optionally substituted, (Ove alkyl)oxy- substituted, (Gis alkyl)amino- optionally substituted, or (C1-6 alkyl)(C1-4 alkyl)amino- optionally substituted, wherein the (C1-β alkyl) of said (C1-6 alkyl) optionally substituted, (C1-6 alkyl)oxy- substituted, (C1-6 alkyl)amino- optionally substituted, or (C1-β alkyl)(C1-4 alkyl)amino- optionally substituted is optionally substituted with 1-4 substituents each independently selected from hydroxyl, -OP(O)(OH)2, -O-PIOXR'R^, -N(Re)(Rj, -OO2(R*), -CON^XRj, optionally substituted phenyl, and an optionally substituted 5-6 membered heteroaryl group,wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -OP(O)(OH)2, -OP(O)(R'R)2, amino, (C1-6 alkyl)amino-, (C1-6 alkyl)(C1-6 alkyl)amino-, -(C1-6 alkyl)-NH2, halo(C1-6 alkyl), hydroxy-(C1-4 alkyl)-, -(C1-4 alkyl)-OP(O)(OH)2, -(C1-4 alkyl)-OP(O)(R1R1)2, halo(C1-4 alkoxy)-, C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, -(C2-4 alkoxy)-OP(O)(OH)2, -(C2-4 alkoxy)-OP(O)(RlR)2, -C1-4 alkyl-(C1-4 alkoxy), and C1-4 alkoxy-(C1-4 alkoxy)-., 2. The compound according to claim 1, wherein, when s is 0 and r is 1, then at least one of X3 and X4 is S or at least one of Xs, Xs and Xg is N.

3. The compound according to any of the preceding claims, wherein the compound has Formula (IA): 1 CQbzn / z / nz / zi / Yl· 251 R14 I CQb7n / 77n7 / =l / YIAI or a pharmaceutically acceptable prodrug, solvate, salt, or tautomer thereof.

4. A compound of Formula (lAj) or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Wi, Xi, Yi, Zi, W2, X2, Y2, Z2, r, s, X3, X4, X5, X6, X9, R3, R5, R14, Ra, Rb, Rc, Rd, Re, Rf, R1 and R are each independently as defined for Formula (lAj); when r is 0, RB1 and RB2 are each independently as defined for Formula (lAj); when s is 0, RC1 is as defined for Formula (lAj); when r is 1, RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and RB2, forms a bonding group, wherein B is a bonding group or B is as defined for Formula (lAj; when s is 1, Wi and Z2 are, each independently, C or N, RC1 and RC2 are, each independently, -CH2-, and D taken together with RC1 and RC2, forms a bonding group, wherein D is as defined for Formula (lAj; R16 is absent, or is H, halogen, or C1-4 alkyl;252 R15 and R17, each independently, are absent, or are H, cyclopropyl, halogen, or C1-4 optionally substituted alkyl, wherein said C1-4 optionally substituted alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; or R15 and R19 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring; R18 and R19 are, each independently, as defined for Formula (lAj; or R17 and R18 taken together with the atom or atoms through which they are connected, form a 5-6 member ring; R9 and Rh are, each independently, as defined for Formula (lAj or R9 and Rh taken together with the atom or atoms through which they are connected, form a 5-6 member ring; and provided that at least one of (i), (ii), or (ii) of Formula (lAj) applies; 5. The compound according to any of the preceding claims, wherein the compound has Formula (I): or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof.

6. The compound according to any of the preceding claims, wherein the compound is of Formula (Vj: 253 I CQb7n / 77n7 / =l / Yl· or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Yi, Y2, Zi, and Z2 are each independently O, S, C, or N; Xi, X2, Wi, and W2 are each independently C or N; X3 and X4 are each independently S or NRf; X5 is N or CRA2; X6 is NoCRA1; X9 is NoCH; R3 and R5 are each independently -CON(Rd)(R), -CH2N(Rd)(Rf), -N(Rd)(R<), -N(RΡΰ)OO(R0, -OH2N(RΡΰ)OO(R0, or one of R3 and R5 is -CON^XRf), -CH^ÍR^ÍR1), -Ν(Ρΰ)(Ρ0, -Ν(Ρΰ)ΟΟ(Ρ0 or ΟΗ2Ν(Ρΰ)ΟΟ(Ρ0, and the other of R3 and R5 is H, -COOH, or -CO2RC; Rc is C1-4 alkyl;RA2 and RA1 are, each independently, H, halogen, amino, amino(C1-4 alkyl)-, hydroxyl, optionally substituted (C1-6 alkyl), or optionally substituted (C1-6 alkyl)oxy, wherein the C1-6 alkyl of said optionally substituted (C1-6 alkyl), or optionally substituted (C1-6 alkyl)oxy is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxy, -MIR^R'), CO2(Rf), -CON^XRf), and -COOH; each Rd is independently H, hydroxyl, or C1-4 alkyl; Re is selected from H, (C1-4 alkyl), -CO(C1-4 alkyl), -OCO(C1-4 alkyl), and -CO2(C1-4 alkyl); each Rf is independently H, hydroxyl, or (C1-4 alkyl); R14 and RC2 are each independently absent, or are C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd;R16 and R17, R18, or R19 are each independently absent, or are H or C1-4 alkyl; and R15, R17, R18, or R19 are each independently absent, or are H, C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2Rc, -CONRcRd, -SO2NRcRd, and -OCONRcRd; provided that at least one of (i), (ii), or (iii) applies: (i) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C; or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C; or (c) Z1 and Y1 are each N, W1 and X1 are each C; or (d) Z2 and Y2 are each N, W2 and X2 are each C; or (e) W1 and X1 are each N, Z1 and Y1 are each C; or (f) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X3 and X4 is S; or X9 is N; or (ii) when (a) Z1, Z2, Y1 and Y2 are each N, W1, W2, X1 and X2 are each C;or (b) W1, W2, X1 and X2 are each N, Z1, Z2, Y1 and Y2 are each C, then R14 is a C1-4 halogen-substituted alkyl, -ORC, -NRcRd, -CO2Rc, -CONRcRd, -SO2NRcRd, and -OCONRcRd where Rc is H; or (iii) when (a) Z1 and Y1 are each N, W1 and X1 are each C; or (b) Z2 and Y2 are each N, W2 and X2 are each C; or (c) W1 and X1 are each N, Z1 and Y1 are each C; or (d) W2 and X2 are each N, Z2 and Y2 are each C, then at least one of X5, Xb, and Xg is N and RA1 or RA2 is halogen, hydroxyl, optionally substituted (C1-6 alkyl), (C1-6 alkyl)oxy-substituted, optionally substituted (C1-6 alkyl)amino-, or optionally substituted (C1-6 alkyl)(C1-4 alkyl)amino-, wherein the alkyl group of said optionally substituted (C1-6 alkyl)oxy-substituted is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxy, -N^XRO, -COXRf), -CONI^IRO, and -COOH.; 7. The compound according to any of the preceding claims, wherein the compound is of Formula (V): R14 or a pharmaceutically acceptable prodrug, solvate, salt, or tautomer thereof.

8. The compound according to any of the preceding claims, wherein W1, X1, Yi, and Z1 are each independently O, S, C, or N. 255 9. The compound according to any of the preceding claims, wherein Wi is O or C.

10. The compound according to any of the preceding claims, wherein Xi is C or N.

11. The compound according to any of the preceding claims, wherein Yi is C or N.

12. The compound according to any of the preceding claims, wherein Zi is O or C.

13. The compound according to any of the preceding claims, wherein W2, X2, Y2, and Z2 are each independently O, S, C, or N.

14. The compound according to any of the preceding claims, wherein W2 is O or C.

15. The compound according to any of the preceding claims, wherein X2 is C or N.

16. The compound according to any of the preceding claims, wherein Y2 is C or N.

17. The compound according to any of the preceding claims, wherein Z2 is O or C.

18. The compound according to any of the preceding claims, wherein X3 and X4 are, each independently, S or NRf.

19. The compound according to any of the preceding claims, wherein X3 is S.

20. The compound according to any of the preceding claims, wherein X3 is NRf.

21. The compound according to any of the preceding claims, wherein X4 is S.

22. The compound according to any of the preceding claims, wherein X4 is NRf.

23. The compound according to any of the preceding claims, wherein r is 1.

24. The compound according to any of the preceding claims, wherein s is 0.

25. The compound according to any of the preceding claims, wherein p is 1.

26. The compound according to any of the preceding claims, wherein RA1 and RA2 are, each independently, H, halogen, hydroxyl, -N(Re)(Rf), -CO2Rf, -N(Rf)CORb, N(R9)SO2(C1-4 alkyl)-N(Re)(Rf), -N(R9)CO(C1-4 alkyl)-N(Rh)(Rf), optionally substituted (C1-e alkyl), optionally substituted (C1-6 alkyl)oxy, optionally substituted (C1-6 alkyl)amino, and optionally substituted (C1-6 alkyl)(C1-4 alkyl)amino, wherein the (C1-e alkyl) of said optionally substituted (C1-6 alkyl), optionally substituted (C1-6 alkyl)oxy, (C1-e alkyl)amino- optionally substituted and (C1-6 alkyl)(C1-4 alkyl)amino optionally substituted is optionally substituted with 1-4 substituents, each independently selected from hydroxyl, Ch alkoxy-, -N(Re)(Rf), -COzCRj, -CON(Re)(Rf), optionally substituted phenyl, and optionally substituted 5-6 membered heteroaryl group,wherein said optionally substituted phenyl or 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (O-6 alkyl)amino-, (Ci-s alkyl)(Ci-6 alkyl)amino-, halo(Ci-6 alkyl), hydroxy-(Ci-4 alkyl)-, halo-(Ci-4 alkoxy)-, Ci4 alkoxy-, hydroxy-(C2-4 alkoxy)-, and C1-4 alkoxy-(Ci-4 alkoxy)-.

27. The compound according to any of the preceding claims, wherein RA1 and RA2 are, each independently, H, halogen, (C1-salkyl)oxy-, hydroxy(C2-6 alkyl)oxy-, HO(O)C-(C2-6 alkyl)oxy-, amino(C2-6 alkyl)oxy-, hydroxyl, amino, or amino(C1-4 alkyl)-.

28. The compound according to any of the preceding claims, wherein RA1 and RA2 are independently H, halogen, hydroxyl, -OCH2CH2CH2OH, -OCH2CH2CH2COOH, OCH2CH2CH2NH2, -OCH3, or -N(Ρθ)(Ργ 29. The compound according to any of the preceding claims, wherein RA2 is (C1-6 alkyl)oxy-substituted, wherein the (Ove alkyl) of said (C1-6 alkyl)oxy-substituted is substituted with hydroxyl.

30. The compound according to any of the preceding claims, wherein RA2 is -OCH2CH2CH2OH.

31. The compound according to any of the preceding claims, wherein s is 0, W1 and Z2 are, each independently, C or N, and RC1 and RC2, each independently, are absent, or are H or C1-4 alkyl.

32. The compound according to any of the preceding claims, wherein r is 1 and RB1 and RB2 are each independently -CH2-, and B, taken together with RB1 and RB2, forms a linking group, wherein B is a linker or B is -halo(Ci-ium alkyl)-, -C1-10 alkyl- optionally substituted, C2-10 alkenyl- optionally substituted, -C2-ium alkynyl- optionally substituted, -C1-6 alkyl-O-Ci-6 alkyl- optionally substituted, -C1-6 alkyl-NRa-Ci-6 alkyl- optionally substituted, C3-6 cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, -C1-4 alkyl-(C3-6 optionally substituted cycloalkyl-C1-4 alkyl, optionally substituted C1-4 alkyl-phenyl-C1-4 alkyl, optionally substituted C1-4 alkyl-(4-6 membered heterocycloalkyl)-C1-4 alkyl, or optionally substituted C1-4 alkyl(5-6 membered heteroaryl)-C1-4 alkyl,wherein the alkyl group of said optionally substituted -C1-10 alkyl-, optionally substituted -C2-10 alkenyl-, optionally substituted -C2-w alkynyl-, optionally substituted -C1-6 alkyl-O-Ci-6 alkyl-, optionally substituted -Ci-6 alkyl-NRa-Ci-6 alkyl-, optionally substituted -Ci-4 alkyl-(C3-6 cycloalkyl) I CQb7n / 77n7 / =l / YIAI 257 optionally substituted Ci-4 alkyl-, optionally substituted -C1-4 alkyl-phenyl-Ci-4 alkyl-, optionally substituted -C1-4 alkyl(4-6 membered heterocycloalkyl)-Ci-4 alkyl-, or optionally substituted -C1-4 alkyl-(56 membered heteroaryl-Ci-4 alkyl)- is optionally substituted with 1 or 2 substituents, each independently selected from halogen, halo(Ci-4 alkyl), -OH, -OP(O)(OH)2, -OP(O)(R'R)2, -ORG, -NH2, -NRcRd, -OCORG, -CO2H, -CO2RC, -SORC, -SO2RC, -CONH2, -CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, -OCONRcRd, -NRdCORc, -NRdSORc, -NRd, and NRdSO2Rc, and the remainder C3.6cycloalkyl, phenyl, 4-6 membered heterocycloalkyl,or optionally substituted 5-6 membered heteroaryl of said C3-e cycloalkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocycloalkyl, optionally substituted 5-6 membered heteroaryl, optionally substituted -C1-4 alkyl-(C3-6 cycloalkyl)-C1-4 alkyl-, optionally substituted -C1-4 alkyl-phenyl-C1-4 alkyl-, optionally substituted C1-4 alkyl-(4-6 membered heterocycloalkyl)-C1-4 alkyl-, or optionally substituted -C1-4 alkyl(5-6 membered heteroaryl) C1-4 alkyl- is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -OP(O)(OH)2, -OP(O)(R'R)2, amino, (C1-4 alkyl)amino-, (C1-4 alkyl(Ci-4 alkyl)amino-, -C1-4 alkyl, halo(Ci-4 alkyl), halo(Ci-4 alkoxy)-, -C1-4 alkoxy-, hydroxy-(C2-4 alkoxy)-, and -C1-4 alkoxy-(Ci-4 alkoxy)-.

33. The compound according to any of the preceding claims, wherein r is 1, RB1 and RB2 are each independently -CH2-, and B is a substituted -C1-10 alkyl- group or a -C1-10 alkyl-, -C2-10 alkenyl-, -C2-10 alkynyl-, -C1-e alkyl-O-C1-6 alkyl-, or unsubstituted -C1-6 alkyl-NRa-C1-6 alkyl- group, wherein said substituted -C1-10 alkyl- group is substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, -OP(O)(OH)2, -O-PCOXR'R^ amino, (C1-4 alkyl)amino, (C1-4 alkyl)(C1-4 alkyl)amino-, halo(C1-4 alkyl), halo(C1-4 alkoxy)-, and C1-4 alkoxy-.

34. The compound according to any of the preceding claims, wherein r is 1, RB1 and RB2 are each independently -CH2-, and B is -CH=CH-, -CH2CH2-, -CH(OH)CH(OH)-, or CH2N(CH3)CH2-.

35. The compound according to any of the preceding claims, wherein r is 1, and B, taken together with RB1 and RB2, forms a -CH2CH=CHCH2-.

36. The compound according to any of the preceding claims, wherein R3 and R5 are, each independently, -CON(Rd)(Rf), -CH2N(Rd)(Rf), -N(Rd)(Rf), -N(Rd)CO(Rf), or CH2N(Rd)CO(Rf).

37. The compound according to any of the preceding claims, wherein R3 and R5 are, each independently, -CON(Rd)(Rf).

38. The compound according to any of the preceding claims, wherein R3 and R5 are each -CONH2.

39. The compound according to any of the preceding claims, wherein R4 and R6 are each H.

40. The compound according to any of the preceding claims, wherein R4 and R6 are, each independently, H, halogen, halo(Ci-4 alkyl), halo(Ci-6 alkoxy)-, hydroxyl, -OP(O)(OH)2, -OP(O)(RiR)2, -NH2, -NRcRc, -NRcRd, -CORC, -CO2RC, -N(Rd)CORG, -N(Rd)SO2Rc, N(R9)SO2(Ci-2alkyl)-N(Rh)(R), -N(R9)CO(Ci-2alkyl)-N(Rh)(Rf), optionally substituted (C1-6 alkyl), optionally substituted (C2-6 alkyl)oxy, optionally substituted (C1-6 alkyl)amino, or optionally substituted (C1-6 optionally substituted alkyl(C1-4 alkyl)amino, wherein the (C1-6 alkyl) of said optionally substituted (C1-6 alkyl), optionally substituted (C1-6 alkyl)oxy, optionally substituted -C1-β alkyl)amino and optionally substituted (C1-6 alkyl)(C1-4 alkyl)amino is optionally substituted with 1-4 substituents, each independently selected from -OH, -OP(O)(OH)2, -OP / OXR'R)^ -ORC, -NH2, -NRCRC, -NRcRd, -CO2H, -CO2Rc, OCORc, -CO2Rc, -SORc, -SO2Rc, -CONH2,-CONRcRd, -SO2NH2, -SO2NRcRd, -OCONH2, OCONRcRd, -NRdCORc, -NRdSORc, -NRdCO2Rc, -NRdSO2Rc, optionally substituted phenyl, optionally substituted 5-6 membered heterocycloalkyl, and optionally substituted 5-6 membered heteroaryl, wherein said optionally substituted phenyl, optionally substituted 5-6 membered heterocycloalkyl, and optionally substituted 5-6 membered heteroaryl is optionally substituted with 1-4 substituents, each independently selected from halogen, hydroxyl, amino, (C1-4 alkyl)amino-, (C1-4 alkyl)(C1-4 alkyl)amino-, C1-4 alkyl, halo(C1-4 alkyl), hydroxy-(C1-4 alkyl)-, (C1-4 alkyl)-OP(O)(OH)2, -(C1-4 alkyl)-OP(O)(R'R)2, halo(Ci-4 alkoxy)-, C1-4alkoxy-, hydroxy-(C2-4 alkoxy)-, (C2-4 alkoxy)-OP(O)(OH)2, -(C2-4 alkoxy)-OP(O)(R'R)2, C1-4 alkoxy-(Ci-4 alkoxy)-, -CORd, -ΟΟΝ^ΧΡ^, and CO2Rd., 41. The compound according to any of the preceding claims, wherein R14 is absent.

42. The compound according to any of the preceding claims, wherein R14 is a halogen, or C1-4 optionally substituted alkyl, wherein said C1-4 optionally substituted alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd.

43. The compound according to any of the preceding claims, wherein R16 is H or absent.

44. The compound according to any of the preceding claims, wherein R16 is C1-4 alkyl.

45. The compound according to any of the preceding claims, wherein R16 is ethyl.

46. ​​The compound according to any of the preceding claims, wherein R15 and R17 are each independently absent.

47. The compound according to any of the preceding claims, wherein R15 and R17 are, each independently, H, cyclopropyl, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, and -OCONRcRd; or R15 and R19 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring. 259 48. The compound according to any of the preceding claims, wherein R15 and R19 taken together with the atom or atoms through which they are connected, form a 5-6 member ring.

49. The compound according to any of the preceding claims, wherein R16 and R17 taken together with the atom or atoms through which they are connected, form a 5-6 member ring.

50. The compound according to any of the preceding claims, wherein R18 and R19 are each independently absent.

51. The compound according to any of the preceding claims, wherein R18 and R19 are, each independently, H, halogen, or optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -COzRc, -CONRcRd, -SO2NRcRd, and -OCONRcRd; or R17 and R18 taken together with the atom or atoms through which they are connected, form a 5-6 membered ring.

52. The compound according to any of the preceding claims, wherein R18 and R19 are, each independently, a halogen, or an optionally substituted C1-4 alkyl, wherein said optionally substituted C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, -CONRcRd, -SO2NRcRd, -CH2-CO2RC, and -OCONRcRd.

53. The compound according to any of the preceding claims, wherein R17 and R18 taken together with the atom or atoms through which they are connected, form a 5-6 member ring.

54. The compound according to any of the preceding claims, wherein R14, R15, R16, R17, R18 and R19 are each independently absent, or are H or C1-4 alkyl.

55. The compound according to any of the preceding claims, wherein Xs is N.

56. The compound according to any of the preceding claims, wherein Xs is CRA2, wherein RA2 is selected from H, halogen, -OCH2CH2CH2OH, -OCH2CH2CH2COOH, OCH2CH2CH2NH2, -OCH3, and -N(Re)(Rf).

57. The compound according to any of the preceding claims, wherein Xs is CRA2, wherein RA2 is selected from -OCH2CH2CH2OH, -OCH2CH2CH2COOH.

58. The compound according to any of the preceding claims, wherein Xb is N.

59. The compound according to any of the preceding claims, wherein Xb is CRA1.

60. The compound according to any of the preceding claims, wherein Xs is N and X6 is CRA1.

61. The compound according to any of the preceding claims, wherein Xb is N and Xs is CRA1. I CQb7n / 77n7 / =l / YIAI 260 62. The compound according to any of the preceding claims, wherein Xe is N and X5 is CRA1, wherein RA1 is -OCH2CH2CH2OH.

63. The compound according to any of the preceding claims, wherein X3 and X4 are, each independently, S or NRf, wherein Rf is H.

64. The compound according to any of the preceding claims, wherein X3 is S and X4 is NRf, wherein Rf is H.

65. The compound according to any of the preceding claims, wherein Xg is N.

66. The compound according to any of the preceding claims, wherein X9 is CR4.

67. The compound according to any of the preceding claims, wherein Xg is CH.

68. The compound according to any of the preceding claims, wherein the compound is of Formula (Vj), Formula (Vb), Formula (Vc), Formula (Vd), Formula (Ve), Formula (V-e1), or Formula (V-e2): 261 I CQb7n / 77n7 / 3 / YIAI or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Xs is N or CRA2; Xe is not CRA1; RA2 and RA1, when present, are each independently a halogen, hydroxyl, optionally substituted (Ci-b alkyl), optionally substituted (Ci-s alkyl)oxy, optionally substituted (Os alkyl)amino, or optionally substituted (C1-6 alkyl)(Ci-4 alkyl)amino, wherein the Ci-ealkyl of said (Ci-ealkyl) optionally substituted or (C1-4 alkyl)oxy-substituted is optionally substituted with 1-4 substituents, each independently selected from the group comprising hydroxyl, C1-4 alkoxy, -N(Re)(Rf), -CC>2(Rj, -CON(Re)(Rf), and -COOH;and X3, X4, RC1, RC2, R3, R5, Re, Rf, R14, R15, R16, R17, R18, and R19, are, each independently, as defined in the Formula (Vj.; 69. The compound according to claim 68, wherein the compound is of Formula (Vb), Formula (Vc), Formula (Vd), Formula (Ve), Formula (V-e1), or Formula (V-e2), or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof.

70. The compound according to any of the preceding claims, wherein the compound is of Formula (Vj), wherein the compound is of Formula (Vf), Formula (V-f1), Formula (V-f2), Formula (V-f3), Formula (V-f4), Formula (V-f5), Formula (V-f6), or (Formula (V-f7): 262 I CQb7n / 77n7 / =l / Y 263 or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Y2 and Z2 are, each independently, O, S, C or N; X2 and W2 are, each independently, C or N; X3, X4, Xs, Xβ, Xθ, R16, RC1, Rc, R3, R5, R17, R18, R19 and Rd are, each independently, as defined in Formula (Vj; and RC2 each independently are absent, or are C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RC, CONRcRd, -SO2NRcRd, and -OCONRcRd.

71. The compound according to claim 70, wherein the compound is of Formula (V-f1), Formula (V-f2), Formula (V-f3), Formula (V-f4), Formula (V-f5), Formula (V-f6), or Formula (V-f7), or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof.

72. The compound according to any of the preceding claims, wherein the compound is of Formula (Vj), Formula (V-g1), Formula (V-g2), Formula (V-g3), Formula (V-g4), Formula (V-g5), Formula (V-g6), or Formula (V-g7): 264 or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Y2 and Z2 are, each independently, O, S, C, or N; X2 and W2 are, each independently, C or N; X3, X4, Xs, Xe, Xg, Rc, RC1, R3, R5, R16, R17, R18, R19, and Rd are, each independently, as defined in Formula (Vj); and RC2 is absent, or is C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -CO2RG, -CONRcRd, -SO2NRGRd, and -OCONRcRd. 265 73. The compound according to claim 72, wherein the compound is of Formula (V-g1), Formula (V-g2), Formula (V-g3), Formula (V-g4), Formula (V-g5), Formula (V-g6), or Formula (V-g7), or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof.

74. The compound according to any of the preceding claims, wherein the compound is of Formula (V'), wherein the compound is of Formula (Vh), Formula (V-h1), Formula (V-h2), Formula (V-h3), Formula (V-h4), Formula (V-h5), Formula (V-h6), or Formula (V-h7): ίOOΟΉ7Π / 77Π7 / 3 / YΙΛΙ 266 or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Yi and Zi are, each independently, O, S, C or N; Xi and Wi are, each independently, C or N; Xs, Χε, Xg, Χε, X4, Rc, R3, R5, R1B, R15, R18, R19, RC1, and Rd are, each independently, as defined in Formula (Vj; and R14 is absent, or is C1-4 alkyl, wherein C1-4 alkyl is optionally substituted with a substituent selected from halogen, -ORC, -NRcRd, -COzR0, -CONRcRd, -SO2NRcRd, and -OCONRcRd.

75. The compound according to claim 74, wherein the compound is of Formula (V-h1), Formula (V-h2), Formula (V-h3), Formula (V-h4), Formula (V-h5), (Formula (V-h6), or Formula (V-h7), or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof.

76. The compound according to any of the preceding claims, wherein the compound is of Formula (Vj), wherein the compound is of Formula (V-i), Formula (V-i1), Formula (V-i2), Formula (V-i3), Formula (V-i4), Formula (V-i5), (Formula (V-i6), or Formula (V-i7): 267 I CQb7n / 77n7 / =l / YIA 268 or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof, wherein: Xs, Xe, Xg, Xs, X4, R3, R5, R16, R18, R19, and RC1 are, each independently, as defined in Formula (V').

77. The compound according to claim 76, wherein the compound is of Formula (V-11), Formula (V-12), Formula (V-13), Formula (V-14), Formula (V-15), Formula (V-16), or Formula (V-17), or a prodrug, solvate, pharmaceutically acceptable salt, or tautomer thereof.

78. The compound according to any of the preceding claims, wherein the compound is not selected from: I CQb7n / 77n7 / =l / YIAI 270 LCQfr7n / 77n7 / q / Yli 271 79. The compound according to any of the above claims, wherein the I CQb7n / 77n7 / =l / YIA compound is not: (E)-N,N'-(but-2-eno-1,4-di¡lb¡s(5-carbamo¡l-7-(2-h¡drox¡ethoxy)-1H-benzo[d]¡midazol-1,2-diyl))bis(4ethyl-2-methyloxazole-5-carboxamide); (E)-N,N'-(but-2-eno-1,4-d¡¡lbis(5-carbamo¡l-7-h¡drox¡-1 H-benzo[d]imidazol-1,2-diyl))bis(4-ethyl-2methyloxazol-5-carboxamide); (E)-N-(5-carbamo¡l-1-(4-(5-carbamo¡l-2-(4-et¡l-2-met¡loxazole-5-carboxamide)-7-hydroxy¡-1Hbenzo[d]¡ m¡dazol-1-yl)but-2-en-1-¡l)-7-methox¡-1H-benzo[d]im¡im¡dazol-2-¡l)-4-et¡l-2-met¡loxazole-5-carboxam¡da; N,N'-((((1 S,2S)-cyclopropano-1,2-diyl)bis(methylene))b¡s(5-carbamo¡l-1 H-benzo[d]imidazol-1,2diyl))b¡s(4-et¡l-2-methyloxazole-5-carboxam¡da); (E)-1,1'-(but-2-eno-1,4-d¡¡l)b¡s(2-(2,5-d¡methylfuran-3-carboxam¡do)-7-methoxy¡-1H-benzo[d]¡midazole5-carboxamide); (E)-N,N'-(hex-3-eno-1,6-diylbis(5-carbamoyl-1 H-benzo[d]imidazol-1,2-diyl))bis(4-ethyl-2-methyloxazole5-carboxamide);(E)-N-(5-carbamoyl-1-(4-(5-carbamoyl-2-(4-ethyl-2-methyloxazol-5-carboxamido)-1H-benzo[d]¡midazol1 -yl)but-2-en-1 -yl)-7-methyl-1 H-benzo[d]im¡dazol-2-yl)-4-ethyl-2-methloxazole-5-carboxam¡da; (E)-N-(5-carbamoyl-1-(4-(5-carbamoyl-2-(2,4-d¡meth¡loxazol-5-carboxamido)-1H-benzo[d]imide zol-1¡l)but-2-en-1-yl)-7-met¡l-1H-benzo[d]¡m¡dazol-2-¡l)-2,4-d¡met¡loxazole-5-carboxam¡da; (E)-N,N'-(but-2-eno-1,4-di¡lb¡s(5-carbamo¡l-7-methoxy¡-1 H-benzo[d]imidazol-1,2-diyl))bis(2,4dimethyloxazol-5-carboxamide); (E)-N,N'-(but-2-eno-1,4-di¡lb¡s(5-carbamoyl-7-methox¡-1 H-benzo[d]imidazol-1,2-diyl))bis(4-ethyl-2methyloxazol-5-carboxamide); 272 (E)-1,1'-(but-2-eno-1,4-diyl)bis(2-(1 -ethyl-1 H-imidazole-5-carboxamido)-7-methoxy-1 Ηbenzo[d]imidazole-5-carboxamide); (E)-1,1'-(but-2-eno-1,4-dül)bis(2-(1 -ethyl-1 H-im¡dazol-2-carboxamido)-7-methox¡-1 Hbenzo[d]imidazol-5-carboxamide);Acid (Z)-4-carbamoyl-1,15-bis(4-et¡l-2-met¡loxazol-5-carboxam¡do)-8,9,16,19-tetrahydro-7H-6,1 0dioxa-2,14,15a,19a-tetraazac¡clopentadeca[3,2,1-cd:8,9,10-c'd']dyneno-12-carboxyl¡co; (E)-1-(4-(5-carbamo¡l-2-(furan-2-carboxamide)-1H-benzo[d]¡m¡dazol-1-¡l)but-2-en-1-¡l)-2-(furan-2carboxamido)-7-methyl-1H-benzo[d]m¡m¡m¡dazol-5-carboxamide; (E)-1 -(4-(5-carbamoyl-2-(pyrazole[1,5-a]p¡r¡dine-2-carboxam¡do)-1 H-benzo[d]imidazole-1 -i I) but-2-e n1 -yl)-7-methyl-2-(pyrazolo[ 1,5-a]ampyr-2-carboxy-1) H-benzo[d]imidazole-5-carboxam¡da; (E)-1-(4-(5-carbamoyl-2-(1-methi 1-1 H-pyrrol-2-carboxam¡do)-1H-benzo[d]¡m¡dazol-1-yl)but-2-en-1-yl)7-methyl-2-(1 -methyl-1 H-pyrrol-2-carboxamido)1 H-benzo[d]imidazole-5-carboxam¡da; (E)-1 -(4-(5-carbamoyl-2-(1 H-pyrrole-2-carboxamido)-1 H-benzo[d]imidazol-1 -yl)but-2-en-1 -yl)-7-methyl2-(1H-pyrrol-2-carboxam¡do)-1H-benzo[d]imidazol-5-carboxamido;(E)-1-(4-(5-carbamo¡l-2-(1-metil-1H-¡ndol-2-carboxam¡do)-1H-benzo[d]¡m¡dazol-1-¡l)but-2-en-1-¡l)7-metil-2-(1 -metil-1 H-indol-2-carboxamido)-1 H-benzo[d]imidazol-5-carboxam¡da; (E)-N-(5-carbamoil-1-(4-(5-carbamo¡l-2-(4-et¡l-2-met¡loxazol-5-carboxam¡do)-7-(3-h¡drox¡propox¡)1H-benzo[d]¡midazol-1-il)but-2-en-1-¡l)-7-metox¡-1H-benzo[d]imidazol-2-¡l)-4-et¡l-2-metiloxazol-5carboxamida; (Z)-1,15-b¡s(4-et¡l-2-met¡loxazol-5-carboxam¡do)-8,9,16,19-tetrah¡dro-7H-6,10-dioxa-2,14,15a,19atetraazaciclopentadeca[3,2,1-cd:8,9,10-c,d,]d¡¡ndeno-4,12-d¡carboxamida; N-(5-carbamoil-1 -(2-((1 R,2R)-2-(2-(5-carbamoil-2-(4-etil-2-met¡loxazol-5-carboxam¡do)-1 Hbenzo[d]¡m¡dazol-1-il)et¡l)c¡cloprop¡l)et¡l)-7-metil-1H-benzo[d]¡m¡dazol-2-¡l)-4-et¡l-2-met¡loxazol-5carboxamida; (E)-N-(5-carbamoil-1-(4-(5-carbamoil-2-(4-et¡l-2-met¡loxazol-5-carboxam¡do)-7-(2-hidrox¡etoxi)-1Hbenzo[d]imidazol-1-il)but-2-en-1-il)-7-metoxi-1H-benzo[d]imidazol-2-il)-4-etil-2-metiloxazol-5-carboxamida;Ácido (E)-2-((5-carbamo¡l-1-(4-(5-carbamo¡l-2-(4-et¡l-2-metiloxazol-5-carboxam¡do)-7-metox¡-1Hbenzo[d]¡m¡dazol-1-¡l)but-2-en-1-¡l)-2-(4-et¡l-2-metiloxazol-5-carboxam¡do)-1H-benzo[d]¡m¡dazol-7il)oxi)acético; Ácido (E)-2-((5-carbamoil-1-(4-(5-carbamoil-2-(4-et¡l-2-met¡loxazol-5-carboxam¡do)-7-(2h¡drox¡etox¡)-1H-benzo[d]¡m¡dazol-1-il)but-2-en-1-¡l)-2-(4-et¡l-2-metiloxazol-5-carboxam¡do)-1Hbenzo[d]im¡dazol-7-il)oxi)acético; (E)-1,15-bis(4-et¡l-2-met¡loxazol-5-carboxamido)-N-(2-hidrox¡et¡l)-8,9,16,19-tetrah¡dro-7H-6,10dioxa-2,14,15a,19a-tetraazac¡clopentadeca[3,2,1-cd:8,9,10-c'd']d¡¡ndeno-4,12-d¡carboxamida; (E)-N-(5-carbamo¡l-1-(4-(5-carbamo¡l-2-(4-et¡l-2-met¡loxazol-5-carboxam¡do)-7-metox¡-1Hbenzo[d]¡m¡dazol-1-¡l)but-2-en-1-¡l)-7-(2-(dimetilam¡no)etox¡)-1H-benzo[d]¡m¡dazol-2-¡l)-4-et¡l-2-met¡loxazol5-carboxamida;o LCQfrzn / zznz / q / YiAi 273 (E)-1 -(4-(5-carbamoyl-2-(1 -(2-h id roxietyl)-3-methyl I-1 H-pyrazole-5-carboxamido)-1 H-benzo[d]imidazol1 -yl) but-2-e n-1 -yl)-2- (1 -eti I-3-methyl-1 H-pyrazole-5-carboxamido)-1 H-benzo[d]imidazole-5-carboxamide.; 80. The compound according to any of the preceding claims, wherein Ring 1 is selected from any one of the following: (1) □ 19 Rc 10 Oí - Z Oí y' (3) R14 R19 <ϊ rc1 . (4) r14 v ,r19 1 z' n -5-(7 । i (5) t 2 z ¿ ul (7) ' d 19 (8) ς r19 ήρ (9) § s-n ta ¡l f^r15 ; (10) , n^r19 mi r^r15 r1 σι co (12) s^r19 <^r15 (13) 'm ha. (14) ax 5 n-%15. (15) -pxr” n-^r15; (16) έ θ'ν (17) t^r15 (18) ^r15 (19) sy^r15 (20) \ (21) (22) - (23) (24) al n^r15 dc1 r ;y (25) -ημ rc! en donde: r14, r15, y son, cada uno independientemente, h, c1-4 alquilo, halógeno o alquilo opcionalmente sustituido, donde dicho sustituido está con un -co2h.

81. The compound according to any of the preceding claims, wherein Ring 1 and Ring 2 are each independently selected from any one of the following: 274 s OX "Kjf (1) -4 ; "Xl (2) X ; 0^ 44 4 (3) XN ; A / °n (4) ; A / °N -Kxji (5) ; (6) (7) ; 44½ (8) N 44 (9)^VN ; X (10) <x; \ 44 11 (11) v-n; 4<s (12) ν ; η , ν^χ 4< π y-n (13) -4 s n-n 44. h (14) ] (15) n 41 n\ (16) z ο ^χθη ίι (17) 4^j (18) j (19) . nl f j] (20) kx (21) (22) 4 (23) χν ξ s-n 4yii (24) san *\4l (25) x 4λ (2β) ε ds (27) 4^s (28) ^y ς xcf3 (29)41 +<xf’ (30) n^ cf3 (31)ηϊ -4? (32) (33) \4 4~~n (34) 44jx (35) θ-d -κ 2 (36) s^x -44 (37) ν-χ π (38) do (39) -4js (40) 'd νη (41) (42) (43) ® χ°; λη (44) x; (45) (46) (47)^, -14 (48) (49) (50) lcqfrzn 77nz q yiai 27582. The compound according to any of the preceding claims, wherein the compound is selected from the compounds listed in Table 1, tautomers thereof, prodrugs thereof, and salts thereof.

83. A pharmaceutical composition comprising the compound according to any of the preceding claims, and a pharmaceutically acceptable excipient.

84. A method of treating or preventing a STING-mediated disease or disorder in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of the compound according to any of the preceding claims, or a STING antibody-agonist conjugate thereof.

85. The compound according to any of the preceding claims, or a STING antibody-agonist conjugate thereof, for use in the treatment or prevention of a STING-mediated disease or disorder in a subject in need thereof.

86. Use of the compound according to any of the preceding claims, or a STING antibody-agonist conjugate thereof, in the preparation of a medicament for the treatment or prevention of a STING-mediated disease or disorder in a subject in need thereof.

87. The method, compound, conjugate, or use according to any of the preceding claims, wherein the STING-mediated disease or disorder is cancer.