초록 ▼

Provided herein are tetrazolone FASN inhibitors of the formula (I): or a pharmaceutically acceptable form thereof; wherein the variables RA, RB and RC are defined herein. Also provided herein are pharmaceutical compositions of the compounds provided herein as well as methods of their use for the t

Provided herein are tetrazolone FASN inhibitors of the formula (I): or a pharmaceutically acceptable form thereof; wherein the variables RA, RB and RC are defined herein. Also provided herein are pharmaceutical compositions of the compounds provided herein as well as methods of their use for the treatment of various disorders such as hyperproliferative disorders, inflammatory disorders, obesity-related disorders and microbial infections.

대표청구항 ▼

1. A method of inhibiting fatty acid synthase (FASN) in a subject, wherein the subject has a FASN-mediated disorder selected from hyperproliferative disorders, inflammatory disorders, obesity related disorders, Type II diabetes mellitus, fatty liver disease, microbial infections, viral infections, b

1. A method of inhibiting fatty acid synthase (FASN) in a subject, wherein the subject has a FASN-mediated disorder selected from hyperproliferative disorders, inflammatory disorders, obesity related disorders, Type II diabetes mellitus, fatty liver disease, microbial infections, viral infections, bacterial infections, fungal infections, parasitic infections, and protozoal infections comprising administering to a subject a therapeutically effective amount of a compound of formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, stereoisomer and/or polymorph thereof;wherein:RA is selected from C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl and 5-14 membered heteroaryl;RB is selected from C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, 3-14 membered heterocyclyl, C6-14 aryl and 5-14 membered heteroaryl;RC is selected from hydrogen, —OH, —ORC1, —ON(RC2)2, —N(RC2)2, —C(═O)RC1, —CHO, —CO2RC1, —C(═O)N(RC2)2, —C(═NRC2)ORC1, —C(═NRC2)N(RC2)2, —SO2RC1, —S(═O)RC1, —Si(RC1)3, C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl;each instance of RC1 is, independently, selected from C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl; andeach instance of RC2 is, independently, selected from hydrogen, —OH, —ORC1, —CN, —C(═O)RC1, —CO2RC1, —SO2RC1, —P(═O)2RC1, —P(═O)(RC1)2, C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two RC2 groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring;or RB and RC together with the nitrogen (N) atom to which each is attached are joined to form a 5-14 membered ring. 2. The method of claim 1, wherein the hyperproliferative disorder is selected from prostate cancer and hepatocellular cancer. 3. A method of inhibiting fatty acid synthase (FASN) in a subject, wherein the subject has a FASN-mediated disorder selected from hyperproliferative disorders, inflammatory disorders, obesity related disorders, Type II diabetes mellitus, fatty liver disease, microbial infections, viral infections, bacterial infections, fungal infections, parasitic infections, and protozoal infections comprising administering to & the subject a therapeutically effective amount of a compound of formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, stereoisomer and/or polymorph thereof; wherein: RA is selected from C6-14 aryl and 5-14 membered heteroaryl;RB is selected from C6-14 aryl and 5-14 membered heteroaryl;RC is selected from —OH, —ORC1, —ON(RC2)2, —N(RC2)2, —C(═O)RC1, —CHO, —CO2RC1, —C(═O)N(RC2)2, —C(═NRC2)ORC1, —C(═NRC2)N(RC2)2, —SO2RC1, —S(═O)RC1, —Si(RC1)3, C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14aryl, and 5-14 membered heteroaryl, with the proviso that RC is not —CH3;each instance of RC1 is, independently, selected from C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl;each instance of RC2 is, independently, selected from hydrogen, —OH, —ORC1, —CN, —C(═O)RC1, —CO2RC1, —SO2RC1, SORC1, P(═O)2RC1, C2-10 alkyl, C2-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two RC2 groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring;or RB and RC together with the nitrogen (N) atom to which each is attached are joined to form a 5-14 membered ring;wherein:RB is substituted with the group: -L-RD wherein:L is a covalent bond or a divalent C1-10 hydrocarbon chain, wherein one, two or three methylene units of L are optionally and independently replaced with one or more —O—, —S—, —NRB8—, —(C═NRB8)—, —C(═O)—, —C(═S)—, —S(═O)—, —S(═O)2—, divalent carbocyclyl, divalent heterocyclyl, divalent aryl or divalent heteroaryl group;RD is selected from —CN, —NO2, —N3, —SO2H, —SO3H, —C(═O)RB7, —CO2H, —CHO, —C(ORB9)2, —CO2RB7, —OC(═O)RB7, —OCO2RB7, —C(═O)N(RB8)2, —OC(═O)N(RB8)2, —NRB8C(═O)RB7, —NRB8CO2RB7, —NRB8C(═O)N(RB8)2, —C(═NRB8)ORB7, —OC(═NRB8)RB7, —OC(═NRB8)ORB7, —C(═NRB8)N(RB8)2, —OC(═NRB8)N(RB8)2, —NRB8C(═NRB8)N(RB8)2, —C(═O)NRB8SO2RB7, —NRB8SO2RB7, —SO2N(RB8)2, —SO2RB7, —SO2ORB7, —OSO2RB7, —S(═O)RB7, —OS(═O)RB7, —C(═S)N(RB8)2, —C(═O)SRB7, —C(═S)SRB7, —SC(═S)SRB7, —P(═O)2RB7, —OP(═O)2RB7, —P(═O)(RB7)2, —OP(═O)(RB7)2, —OP(═O)(ORB9)2, —P(═O)2N(RB8)2, —OP(═O)2N(RB8)2, —P(═O)(NRB8)2, —OP(═O)(NRB8)2, —NRB8P(═O)(ORB9)2, —NRB8P(═O)(NRB8)2, —B(ORB9)2, —BRB7(ORB9), and tetrazolyl;each instance of RB7 is, independently, selected from C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl;each instance of RB8 is, independently, selected from hydrogen, —OH, —ORB7, —N(RB9)2, —CN, —C(═O)RB7, —C(═O)N(RB9)2, —CO2RB7, —SO2RB7, —C(═NRB9)ORB7, —C(═NRB9)N(RB9)2, —SO2N(RB9)2, —SO2RB9, —SO2ORB9, —SORB7, —C(═S)N(RB9)2, —C(═O)SRB9, —C(═S)SRB9, —P(═O)2RB7, —P(═O)(RB7)2, —P(═O)2N(RB9)2, —P(═O)(NRB9)2, C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two RB8 groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; andeach instance of RB9 is, independently, selected from hydrogen, C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two RB9 groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring. 4. The method of claim 3, wherein L is a covalent bond. 5. The method of claim 3, wherein L is a divalent C1-10 hydrocarbon chain, wherein one methylene unit of L is optionally and independently replaced with a divalent carbocyclyl, divalent heterocyclyl, divalent aryl or divalent heteroaryl group. 6. The method of claim 3, wherein RD is selected from —CN, —NO2, —SO2H, —SO3H, —C(═O)RB7, —CO2H, —CHO, —CO2RB7, —C(═O)N(RB8)2, —C(═NRB8)ORB7, —C(═NRB8)N(RB8)2, —C(═O)NRB8SO2RB7, —SO2N(RB8)2, —SO2RB7, —SO2ORB7, —S(═O)RB7, —C(═S)N(RB8)2, —C(═O)SRB7, —C(═S)SRB7, —P(═O)2RB7, —P(═O)(RB7)2, —P(═O)2N(RB8)2, —P(═O)(NRB8)2, —B(ORB9)2, —BRB7(ORB9) and tetrazolyl. 7. The method of claim 6, wherein RD is selected from —C(═O)RB7, —CO2H, —CHO, —CO2RB7, —C(═O)N(RB8)2, —C(═NRB8)ORB7, —C(═NRB8)N(RB8)2, —C(═O)NRB8SO2RB7, —C(═S)N(RB8)2, —C(═O)SRB7 and —C(═S)SRB7. 8. The method of claim 7, wherein RD is selected from —C(═O)RB7, —CO2H, —CHO, and —CO2RB7. 9. The method of claim 8, wherein RD is —CO2H. 10. The method of claim 3, wherein RB is further substituted with the group: —RE wherein:RE is selected from halogen, —OH, —ORB10, —ON(RB11)2, —N(RB11)2, —N(ORB12)RB12, —SH, —SRB10, —SSRB12, —OC(═O)RB10, —OCO2RB10, —OC(═O)N(RB11)2, —NRB11C(═O)RB10, —NRB11CO2RB10, —NRB11C(═O)N(RB11)2, —OC(═NRB11)RB10, —OC(═NRB11)ORB10, —OC(═NRB11)N(RB11)2, —NRB11(═NRB11)N(RB11)2, —NRB11SO2RB10, —OSO2RB10, —OS(═O)RB10, —Si(RB10)3, —OSi(RB10)3, —SC(S)SRB10, —OP(═O)2RB10, —OP(═O)(RB10)2, —OP(═O)(ORB12)2, —OP(═O)2N(RB11)2, —OP(═O)(NRB11)2, —NRB11P(═O)(ORB12)2, —NRB11P(═O)(NRB11)2, —P(RB12)2, —P(RB12)3, —OP(RB12)2, —OP(RB12)3, 3-14 membered heterocyclyl and 5-14 membered heteroaryl, wherein the point of attachment of the 3-14 membered heterocyclyl or 5-14 membered heteroaryl group is on a nitrogen atom;each instance of RB10 is, independently, selected from C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl;each instance of RB11 is, independently, selected from hydrogen, —OH, —ORB10, —N(RB12)2, —CN, —C(═O)RB10, —C(═O)N(RB12)2, —CO2RB10, —SO2RB10, —C(═NRB12)ORB10, —C(═NRB12)N(RB12)2, —SO2N(RB12)2, —SO2RB12, —SO2ORB12, —SORB10, —C(═S)N(RB12)2, —C(═O)SRB12, —C(═S)SRB12, —P(═O)2RB10, —P(═O)(RB10)2, —P(═O)2N(RB12)2, —P(═O)(NRB12)2, C1-10alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two RB11 groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; andeach instance of RB12 is, independently, selected from hydrogen, C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two RB12 groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring. 11. The method of claim 10, wherein RE is selected from halogen, —OH, —ORB10, —ON(RB11)2, —N(RB11)2, —N(ORB12)RB12, —SH, —SRB10, —SSRB12, —Si(RB10)3, —OSi(RB10)3, —P(RB12)2, —P(RB12)3, —OP(RB12)2, —OP(RB12)3, 3-14 membered heterocyclyl and 5-14 membered heteroaryl, wherein the point of attachment of the 3-14 membered heterocyclyl or 5-14 membered heteroaryl group is on a nitrogen atom. 12. The method of claim 11, wherein RE is selected from halogen, —ORB10 and —N(RB11)2. 13. The method of claim 3, wherein RC is selected from C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl. 14. The method of claim 13, wherein RC is C3-10 alkyl. 15. The method of claim 13, wherein RC is C3-10 carbocyclyl. 16. The method of claim 3, wherein RA is C6-14 aryl or 5-14 membered heteroaryl, and RB is C6-14 aryl. 17. The method of claim 16, wherein RA is C6-14 aryl and RB is C6-14 aryl. 18. The method of claim 16, wherein RA is 5-14 membered heteroaryl and RB is C6-14 aryl. 19. The method of claim 3, wherein the compound is of the formula (II): or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, stereoisomer and/or polymorph thereof;wherein each group W—R1, W—R2, W—R3, W—R4, and W—R5 independently represents either a nitrogen atom (N) or C—R1, C—R2, C—R3, C—R4, or C—R5, respectively; andwherein R1, R2, R3, R4 and R5 are, independently, selected from the group consisting of hydrogen, halogen, —CN, —NO2, —N3, —SO2H, —SO3H, —OH, —ORA1, —ON(RA2)2, —N(RA2)2, —N(ORA3)RA3, —SH, —SRA1, —SSRA3, —C(═O)RA1, —CO2H, —CHO, —C(ORA3)2, —CO2RA1, —OC(═O)RA1, —OCO2RA1, —C(═O)N(RA2)2, —OC(═O)N(RA2)2, —NRA2C(═O)RA1, —NRA2CO2RA1, —NRA2C(═O)N(RA2)2, —C(═NRA2)ORA1, —OC(═NRA2)RA1, —OC(═NRA2)ORA1, —C(═NRA2)N(RA2)2, —OC(═NRA2)N(RA2)2, —NRA2C(═NRA2)N(RA2)2, —C(═O)NRA2SO2RA1, —NRA2SO2RA1, —SO2N(RA2)2, —SO2RA1, —SO2ORA1, —OSO2RA1, —S(═O)RA1, —OS(═O)RA1, —Si(RA1)3, —OSi(RA1)3—C(═S)N(RA2)2, —C(═O)SRA1, —C(═S)SRA1, —SC(═S)SRA1, —P(═O)2RA1, —OP(═O)2RA1, —P(═O)(RA1)2, —OP(═O)(RA1)2, —OP(═O)(ORA3)2, —P(═O)2N(RA2)2, —OP(═O)2N(RA2)2, —P(═O)(NRA2)2, —OP(═O)(NRA2)2, —NRA2P(═O)(ORA3)2, —NRA2P(═O)(NRA2)2, -—P(RA3)2, —P(RA3)3, —OP(RA3)2, —OP(RA3)3, —B(ORA3)2, or —BRA1(ORA3), C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl; or one or more of R1 and R2, R2 and R3, R3 and R4 or R4 and R5 are joined to form a C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl or 5-14 membered heteroaryl ring;each instance of RA1 is, independently, selected from C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl;each instance of RA2 is, independently, selected from hydrogen, —OH, —ORA1, —N(RA3)2, —CN, —C(═O)RA1, —C(═O)N(RA3)2, —CO2RA1, —SO2RA1, —C(═NRA3)ORA1, —C(═NRA3)N(RA3)2, —SO2N(RA3)2, —SO2RA3, —SO2ORA3, —SORA1, —C(═S)N(RA3)2, —C(═O)SRA3, —C(═S)SRA3, —P(═O)2RA1, —P(═O)(RA1)2, —P(═O)2N(RA3)2, —P(═O)(NRA3)2, C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two RA2 groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; andeach instance of RA3 is, independently, selected from hydrogen, C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two RA3 groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring;wherein each group W—R6, W—R7, W—R8, W—R9, and W—R10 independently represents either a nitrogen atom (N) or C—R6, C—R7, C—R8, C—R9, or C—R10, respectively;R6, R7, R7, R9 and R10 are, independently, selected from the group consisting of hydrogen, halogen, —CN, —NO2, —N3, —SO2H, —SO3H, —OH, —ORB1, —ON(RB2)2, —N(RB2)2, —N(ORB3)RB3, —SH, —SRB1, —SSRB3, —C(═O)RB1, —CO2H, —CHO, —C(ORB3)2, —CO2RB1, —OC(═O)RB1, —OCO2RB1, —C(═O)N(RB2)2, —OC(═O)N(RB2)2, —NRB2C(═O)RB1, —NRB2CO2RB1, —NRB2C(═O)N(RB2)2, —C(═NRB2)ORB1, —OC(═NRB2)RB1, —OC(═NRB2)ORB1, —C(═NRB2)N(RB2)2, —OC(═NRB2)N(RB2)2, —NRB2C(═NRB2)N(RB2)2, —C(═O)NRB2SO2RB1, —NRB2SO2RB1, —SO2N(RB2)2, —SO2RB1, —SO2ORB1, —OSO2RB1, —S(═O)RB1, —OS(═O)RB1, —Si(RB1)3, —OSi(RB1)3—C(═S)N(RB2)2, —C(═O)SRB1, —C(═S)SRB1, —SC(S)SRB1, —P(═O)2RB1, —OP(═O)2RB1, —P(═O)(RB1)2, —OP(═O)(RB1)2, —OP(═O)(ORB3)2, —P(═O)2N(RB2)2, —OP(═O)2N(RB2)2, —P(═O)(NRB2)2, —OP(═O)(NRB2)2, —NRB2P(═O)(ORB3)2, —NRB2P(═O)(NRB2)2, —P(RB3)2, —P(RB3)3, —OP(RB3)2, —OP(RB3)3, —B(ORB3)2, —BRB1(ORB3), C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, 5-14 membered heteroaryl, -L-RD and —RE; or one or more of R6 and R7, R7 and R8, R8 and R9 or R9 and R10 are joined to form a C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl or 5-14 membered heteroaryl ring; or R10 and RC are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring;wherein at least one of R6, R7, R8, R9, and R10 is the group -L-RD;each instance of RB1 is, independently, selected from C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl;each instance of RB2 is, independently, selected from hydrogen, —OH, —ORB1, —N(RB3)2, —CN, —C(═O)RB1, —C(═O)N(RB3)2, —CO2RB1, —SO2RB1, —C(═NRB3)ORB1, —C(═NRB3)N(RB3)2, —SO2N(RB3)2, —SO2RB3, —SO2ORB3, —SORB1, —C(═S)N(RB3)2, —C(═O)SRB3, —C(═S)SRB3, —P(═O)2RB1, —P(═O)(RB1)2, —P(═O)2N(RB3)2, —P(═O)(NRB3)2, C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two RB2 groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring;each instance of RB3 is, independently, selected from hydrogen, C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two RB3 groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring;L is a covalent bond or a divalent C1-10 hydrocarbon chain, wherein one, two or three methylene units of L are optionally and independently replaced with one or more —O—, —S—, —NRB8—, —(C═NRB8)—, —C(═O)—, —C(═S)—, —S(═O)—, —S(═O)2—, divalent carbocyclyl, divalent heterocyclyl, divalent aryl or divalent heteroaryl group; andwherein RD is selected from —CN, —NO2, —N3, —SO2H, —SO3H, —C(═O)RB7, —CO2H, —CHO, —C(ORB9)2, —CO2RB7, —OC(═O)RB7, —OCO2RB7, —C(═O)N(RB8)2, —OC(═O)N(RB8)2, —NRB8C(═O)RB7, —NRB8CO2RB7, —NRB8C(═O)N(RB8)2, —C(═NRB8)ORB7, —OC(═NRB8)RB7, —OC(═NRB8)ORB7, —C(═NRB8)N(RB8)2, —OC(═NRB8)N(RB8)2, —NRB8C(═NRB8)N(RB8)2, —C(═O)NRB8SO2RB7, —NRB8SO2RB7, —SO2N(RB8)2, —SO2RB7, —SO2ORB7, —OSO2RB7, —S(═O)RB7, —OS(═O)RB7, —C(═S)N(RB8)2, —C(═O)SRB7, —C(═S)SRB7, —SC(═S)SRB7, —P(═O)2RB7, —OP(═O)2RB7, —P(═O)(RB7)2, —OP(═O)(RB7)2, —OP(═O)(ORB9)2, —P(═O)2N(RB8)2, —OP(═O)2N(RB8)2, —P(═O)(NRB8)2, —OP(═O)(NRB8)2, —NRB8P(═O)(ORB9)2, —NRB8P(═O)(NRB8)2, —B(ORB9)2, —BRB7(ORB9) and tetrazolyl;each instance of RB7 is, independently, selected from C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl;each instance of RB8 is, independently, selected from hydrogen, —OH, —ORB7, —N(RB9)2, —CN, —C(═O)RB7, —C(═O)N(RB9)2, —CO2RB7, —SO2RB7, —C(═NRB9)ORB7, —C(═NRB9)N(RB9)2, —SO2N(RB9)2, —SO2RB9, —SO2ORB9, —SORB7, —C(═S)N(RB9)2, —C(═O)SRB9, —C(═S)SRB9, —P(═O)2RB7, —P(═O)(RB7)2, —P(═O)2N(RB9)2, —P(═O)(NRB9)2, C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two RB8 groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring; andeach instance of RB9 is, independently, selected from hydrogen, C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two RB9 groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring;RE is selected from halogen, —OH, —ORB10, —ON(RB11)2, —N(RB11)2, —N(ORB12)RB12, —SH, —SRB10, —SSRB12, —OC(═O)RB10, —OCO2RB10, —OC(═O)N(RB11)2, —NRB11C(═O)RB10, —NRB11CO2RB10, —NRB11C(═O)N(RB11)2, —OC(═NRB11)RB10, —OC(═NRB11)ORB10, —OC(═NRB11)N(RB11)2, —NRB11C(═NRB11)N(RB11)2, —NRB11SO2RB10, —OSO2RB10, —OS(═O)RB10, —Si(RB10)3, —OSi(RB10)3, —SC(S)SRB10, —OP(═O)2RB10, —OP(═O)(RB10)2, —OP(═O)(ORB12)2, —OP(═O)2N(RB11)2, —OP(═O)(NRB11)2, —NRB11P(═O)(ORB12)2, —NRB11P(═O)(NRB11)2, —P(RB12)2, —P(RB12)3, —OP(RB12)2, —OP(RB12)3, 3-14 membered heterocyclyl and 5-14 membered heteroaryl, wherein the point of attachment of the 3-14 membered heterocyclyl or 5-14 membered heteroaryl group is on a nitrogen atom;each instance of RB10 is, independently, selected from C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl;each instance of RB11 is, independently, selected from hydrogen, —OH, —ORB10, —N(RB12)2, —CN, —C(═O)RB10, —C(═O)N(RB12)2, —CO2RB10, —SO2RB10, —C(═NRB12)ORB10, —C(═NRB12)N(RB12)2, —SO2N(RB12)2, —SO2RB12, —SO2ORB12, —SORB10, —C(═S)N(RB12)2, —C(═O)SRB12, —C(═S)SRB12, —P(═O)2RB10, —P(═O)(RB10)2, —P(═O)2N(RB12)2, —P(═O)(NRB12)2, C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two RB11 groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring;each instance of RB12 is, independently, selected from hydrogen, C1-10 alkyl, C1-10 perhaloalkyl, C1-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two RB12 groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring;RC is selected from —OH, —ORC1, —ON(RC2)2, —N(RC2)2, —C(═O)RC1, —CHO, —CO2RC1, —C(═O)N(RC2)2, —C(═NRC2)ORC1, —C(═NRC2)N(RC2)2, —SO2RC1, —S(═O)RC1, —Si(RC1)3, C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, with the proviso that RC is not —CH3;each instance of RC1 is, independently, selected from C1-10 alkyl, C1-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl; andeach instance of RC2 is, independently, selected from hydrogen, —OH, —ORC1, —CN, —C(═O)RC1, —CO2RC1, —SO2RC1, SORC1, —P(═O)2RC1, —P(═O)(RC1)2, C2-10 alkyl, C2-10 perhaloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-14 membered heteroaliphatic, C3-10 carbocyclyl, 3-14 membered heterocyclyl, C6-14 aryl, and 5-14 membered heteroaryl, or two RC2 groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring. 20. The method of claim 19, wherein at least one of R6, R7, R8, R9 and R10 is the group —RE. 21. The method of claim 3, wherein the FASN-mediated disorder is a microbial infection. 22. The method of claim 21, wherein the microbial infection is a viral infection. 23. The method of claim 22, wherein the viral infection is an infection with an enveloped virus or a picornavirus. 24. The method of claim 22, wherein the viral infection is selected from HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-8, HMCV, CVB3, influenza type A, influenza type B, RSV, PIV, measles virus, rhinovirus, adenovirus, HMPV, SARS virus, vaccinia virus, cowpox virus, ectomelia virus, monkeypox virus, rabbitpox virus, HBV, HCV, papillomavirus, BK virus, VEE virus, Rift Valley fever virus, Tavaribe virus, Yellow fever virus, West Nile virus, dengue virus, PTV or Pichinde virus. 25. The method of claim 24, wherein the viral infection is infection with HCV or dengue virus. 26. The method of claim 22, which further comprises administration of one or more additional anti-viral agents. 27. The method of claim 26, wherein the additional anti-viral agent is an interferon, a protease inhibitor, an integrase inhibitor, a reverse transciptase inhibitor, or a combination thereof. 28. The method of claim 26, wherein the additional anti-viral agent is an interferon, ribavirin or a combination thereof. 29. The method of claim 28, wherein the interferon is interferon type III, interferon type II, interferon type I, peginterferon alfa-2a, peginterferon alfa-2b, standard interferon alfa-2a, standard interferon alfa-2b, consensus interferon, interferon alfacon-1, ALBUFERON, omega interferon, interferon gamma-1b, lymphoblastoid interferon tau, or a combination thereof. 30. The method of claim 21, wherein the microbial infection is a bacterial infection. 31. The method of claim 30, wherein the bacterial infection is selected from Helicobacter pyloris, Borelia burgdorferi, Legionella pneumophilia, Mycobacteria tuberculosis, M. avium, M. intracellulare, M. kansaii, M. gordonae, Staphylococcus aureus, Neisseria gonorrhoeae, Neisseria meningitidis, Listeria monocytogenes, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus viridans, Streptococcus faecalis, Streptococcus bovis, Streptococcus pneumoniae, Haemophilus influenzae, Bacillus antracis, corynebacterium diphtheriae, Erysipelothrix rhusiopathiae, Clostridium perfringers, Clostridium tetani, Enterobacter aerogenes, Klebsiella pneumoniae, Pasturella multocida, Fusobacterium nucleatum, Streptobacillus moniliformis, Treponema pallidium, Treponema pertenue, Leptospira, Rickettsia, Actinomyces israelli or a combination thereof. 32. The method of claim 31, wherein the bacterial infection is Mycobacteria tuberculosis. 33. The method of claim 30, wherein the compound is: or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, stereoisomer and/or polymorph thereof. 34. The method of claim 21, wherein the microbial infection is a fungal infection. 35. The method of claim 34, wherein the fungal infection is an infection with aspergilliosis, crytococcosis, sporotrichosis, coccidioidomycosis, paracoccidioidomycosis, histoplasmosis, blastomycosis, zygomycosis or candidiasis. 36. The method of claim 21, wherein the microbial infection is a parasitic or protozoal infection. 37. The method of claim 36, wherein the parasitic or protozoal infection is an infection with P. falcifarium, P. ovale, P. vivax, P. malariae, L. donovari, L. infantum, L. aethiopica, L. major, L. tropica, L. mexicana, L. braziliensis, T. Gondii, B. microti. B. divergens, B. coli, B. hominis, C. parvum, C. cayetanensis, D. fragilis, E. histolytica, I. belli, S. mansonii, S. haematobium, Trypanosoma ssp. Toxoplasma ssp., O. volvulus, Babesia bovis, Babesia canis, Banesia Gibsoni, Besnoitia darlingi, Cytauxzoon felis, Eimeria ssp., Hammondia ssp., T. canis, Cestoda, Theileria ssp. or a combination thereof. 38. The method of claim 36, wherein the parasitic or protozoal infection causes malaria, babesiosis, trypanosomiasis, American trypanosomiasis, leishmaniasis, toxoplasmosis, meningoencephalitis, keratitis, amebiasis, giardiasis, cryptosporidiosis, isosporiasis, cyclosporiasis, microsporidiosis, ascariasis, trichuriasis, ancylostomiasis, strongyloidiasis, toxocariasis, trichinosis, lymphatic filariasis, onchocerciasis, filariasis, schistosomiasis or dermatitis caused by animal schistosomes. 39. The method of claim 38, wherein the parasitic or protozoal infection causes malaria. 40. The method of claim 38, wherein the parasitic or protozoal infection causes leishmaniasis, babesiosis, toxoplasmosis or trypanosomiasis. 41. The method of claim 3, wherein the FASN-mediated disorder is a hyperproliferative disorder. 42. The method of claim 41, wherein the hyperproliferative disorder is cancer. 43. The method of claim 42, wherein the cancer is selected from bladder cancer, brain cancer, breast cancer, colorectal cancer, esophageal cancer, endometrial cancer, gastric cancer, gastrointestinal stromal tumor, kidney cancer, liver cancer, lung cancer, mesothelioma, multiple myeloma, neuroblastoma, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, Paget's disease of the vulva, retinoblastoma, soft tissue sarcoma, skin cancer or thyroid cancer. 44. The method of claim 42, wherein the cancer is pancreatic cancer. 45. The method of claim 42, wherein the cancer is selected from mesothelioma, multiple myeloma, neuroblastoma, Paget's disease, retinoblastoma, leukemia, myelodisplastic syndrome, and soft tissue sarcoma. 46. The method of claim 42, which further comprises administration of one or more anti-cancer agents. 47. The method of claim 3, wherein the FASN-mediated disorder is an inflammatory disorder. 48. The method of claim 47, wherein the inflammatory disorder is selected from anemia, asthma, arteritis, arthritis, chronic obstructive pulmonary disease, dermatitis, gastroesophageal reflux disease, Crohn's disease, inflammatory bowel syndrome, multiple sclerosis, psoriasis and an autoimmune disease. 49. The method of claim 3, wherein the FASN-mediated disorder is an obesity related disorder. 50. The method of claim 49, wherein the obesity related disorder is selected from Type II diabetes mellitus, elevated blood pressure, elevated cholesterol levels, ischemic heart disease, arterial vascular disease, angina, myocardial infarction, stroke, migraines, congestive heart failure, deep vein thrombosis, pulmonary embolism, gall stones, gastroesophagael reflux disease, obstructive sleep apnea, obesity hypoventilation syndrome, asthma, gout, poor mobility, back pain, erectile dysfunction, urinary incontinence, liver injury, fatty liver, and chronic renal failure. 51. The method of claim 3, wherein the FASN-mediated disorder is Type II diabetes mellitus. 52. The method of claim 3, wherein the FASN-mediated disorder is fatty liver disease. 53. The method of claim 3, wherein the compound is: or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, stereoisomer and/or polymorph thereof. 54. The method of claim 3, wherein the compound is: or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, stereoisomer and/or polymorph thereof. 55. The method of claim 3, wherein the hyperproliferative disorder is selected from prostate cancer and hepatocellular cancer. 56. The method of claim 55, wherein the compound is 57. A method of treating pancreatic cancer in a subject comprising administering to the subject a therapeutically effective amount of compound: or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, stereoisomer and/or polymorph thereof.