Compounds useful as chemokine receptor antagonists

A method of inhibiting Chemokine Receptor activity in (a) a subject or (b) a biological sample;

• which method comprises administering to said subject, or contacting said biological sample with a compound having the formula:
• or a pharmaceutically acceptable salt thereof, wherein:
• x and y are each independently 1 or 2, provided that x and y are not simultaneously 2;
• R1 is fluoro, —R3, —OR4, —SR4, —COOR4, —COR4, —CON(R4)2, —N(R4)2, —SO2N(R4)2, —NR4SO2R3, —NR4COR4, NR4CON(R4)2, —CON(R4)2, —OCOR4, or —OSO2R4;
• R3 is an optionally substituted group selected from C1-C6aliphatic or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• each occurrence of R4 is independently hydrogen or an optionally substituted group selected from C1-C6aliphatic or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two R40n the same nitrogen atom, taken together with the nitrogen atom, form an optionally substituted 3-6-membered saturated, partially saturated, or aromatic ring having 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• ring A is substituted with q occurrences of RA, wherein q is 0-2 and each occurrence of RA is independently fluoro, —SO2N(RC)2, —ORC, —SRC, —SO2RC, —CORC, —CO2RC, —N(RC)2, —CON(RC)2, —N(RC)CORC, —N(RC)CO2RC, —N(RC)CON(RC)2, or an optionally substituted group selected from C, C6aliphatic or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two occurrences of RA, or RA and R1, taken together with their intervening atom(s), form an optionally substituted spiro or fused 3-6-membered saturated or partially unsaturated ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein each occurrence of RC is independently hydrogen or an optionally substituted group selected from C1-C6aliphatic or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two occurrences of RC, taken together with the nitrogen atom to which they are bound, form an optionally substituted 3-6-membered saturated, partially unsaturated, or aromatic ring having 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• ring B is substituted with r occurrences of —RB or -L-RB, wherein r is 0-2, L is a C1-4 alkylene and each occurrence of RB is independently fluoro, —ORD, —SRD, CORD, —CO2RD, —N(RD)2, —CON(RD)2, —N(RD)CORD, or an optionally substituted group selected from C1-C6aliphatic or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two occurrences of RB, taken together with their intervening atom(s), form an optionally substituted spiro, fused or bridged 3-6-membered saturated, partially unsaturated, or aromatic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• wherein each occurrence of RD is independently hydrogen or an optionally substituted group selected from C1-C6aliphatic or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two occurrences of RD, taken together with the nitrogen atom to which they are bound, form an optionally substituted 3-6-membered saturated, partially unsaturated, or aromatic ring having 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• n is 1 or 2;
• R is -T-Cy2 or -Cy2,
• wherein T, when present, is a C1-C3alkylene chain, wherein the alkylene chain is substituted with 0 or 1 occurrence of R5a, and 0, 1, or 2 independent occurrences of R5b, and wherein one or more methylene units in the C1-C3alkylene chain, as valency and stability permit, is optionally replaced by one or more independent occurrences of —CR5c═CR5c—, —CO—, —SO2—, —O—, —S—, or —NR5c—;
• R5, is halogen, —CN, —OR5c, —N(R5c)2, —SR5c, or an optionally substituted group selected from C1-C6aliphatic, or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• R5b is an optionally substituted group selected from C1-C6aliphatic, or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• R5c is hydrogen, or an optionally substituted group selected from C1-C4aliphatic, or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two occurrences of R5c, taken together with the nitrogen atom to which they are bound, form an optionally substituted 3-6-membered saturated, partially unsaturated, or aromatic ring having 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• Cy2 is an optionally substituted group selected from a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered partially unsaturated, or aromatic bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• wherein Cy2 is substituted with m independent occurrences of —R, -G-R6a, or -V-G-R6a, and k occurrences of ═O, ═S, ═NR7a, ═NR7b, —R6b, -G-R6b, or -V-G-R6b, wherein:
• m is 0-3;
• k is 0-2;
• V is —O—, —N(R7a)—, —S—, —SO—, —SO2—, —SO2N(R7a), —N(R7a)SO2—, —CO—, —CON(R7a)—, —N(R7a)CO—, or —CO2—;
• G is an optionally substituted straight or branched C1-C4alkylene chain that is optionally replaced by —CR7a═CR7a—, —O—, —N(R7a)—, —S—, —SO—, —SO2—, —SO2N(R7a)—, —N(R7a)SO2—, —CO—, —CON(R7a)—, —N(R7a)CO—, or —CO2—, provided that the replacing group is not directly bonded to V, —R6, or —R6b;
• each occurrence of —R6a is independently optionally substituted C1-C6 aliphatic, halogen, —OR1, —CN, —NO2, —SR7a, —SO2N(R7a)2, NR7aSO2R7b, —SO2R7a COR7a CO R7a N(R7a)2, CON(R7)2, —N(R7a)COR7a, —N(R7a)CO2R7a, or —N(R7a)CON(R7a)2;
• each occurrence of —R6b is independently —OR7b, —SR7b, —SO2N(R7)(R7c), NR7cSO2R7b, —SO2R7b, —CORm, CO2Rh, —N(R7b)(R7c), —CON(R7)(R7c), N(R7c)COR7b, N(R7c)CO2R7b, —N(R7c)CON(R7c)(R7c), or an optionally substituted group selected from a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered saturated, partially unsaturated, or aromatic bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or two occurrences of R6b, taken together with their intervening atom(s), form a spiro, fused, or bridged optionally substituted 5-7-membered saturated, partially unsaturated, or aromatic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• each occurrence of R7, is hydrogen or an optionally substituted C1-C6aliphatic group;
• each occurrence of R7b is an optionally substituted group selected from a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered saturated, partially unsaturated, or aromatic bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• and
• each occurrence of R7c is hydrogen or an optionally substituted group selected from a C1-C6aliphatic group, a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered saturated, partially unsaturated, or aromatic bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or
• R7b and R7c, taken together with the nitrogen atom to which they are bound, form an optionally substituted 3-6-membered saturated, partially unsaturated, or aromatic ring having 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• X is N or CR8,
• wherein R8 is fluoro, —R9, —OR9, —N(R9)2, —SR9, —OCOR9, —COOR9, —CN, —CON(R9)2, —COR9, —SO2R9, —SOR9, —NR9SO2R9, or —SO2N(R9)2, wherein each occurrence of R9 is independently hydrogen or an optionally substituted C1-C6aliphatic group;
• or
• when X is CR8, R8 and R2, taken together with the carbon atom to which they are bound, form an optionally substituted 3-6-membered spiro ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• Q is a C1-C3alkylene chain, wherein the alkylene chain is substituted with 0 or 1 occurrence of R5d, and 0, 1, or 2 independent occurrences of R5, wherein one or more methylene units in the C1-C3alkylene chain, as valency and stability permit, is optionally replaced by one or more independent occurrences of —CR5f═CR5f—, —CO—, —SO2—, —O—, —S—, or —NR5f—, wherein R5d is R5e—, R5e is R5b, and R5f is R5c;
• Cy1 is an optionally substituted group selected from a 5-8-membered partially unsaturated or aromatic unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-14-membered partially unsaturated or aromatic bicyclic or tricyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• wherein Cy1 is substituted with p independent occurrences of —R10a, -J-R10a, or W-J-R10a, and j occurrences of ═O, ═S, ═NR11a, ═NR11b, R10b, -J-R10b, or W-J-R10b, wherein:
• p is 0-3;
• j is 0-2;
• W is —O—, —N(R11a)—, —S—, —SO—, —SO2—, —SO2N(R11a)—, —N(R11a)SO2—, —CO—, —CON(R11a)—, —N(R11a)CO—, or —CO2—;
• J is an optionally substituted straight or branched C1-C4alkylene chain that is optionally replaced by —CR11a═CR11a—, —O—, —N(R11a), —S—, —SO—, —SO2—, —SO2N(R11a)—, —N(R11a)SO2—, —CO—, —CON(R11a)—, —N(R11a)CO—, or —CO2—, provided that the replacing group is not directly bonded to W, —R10a, or —R10b;
• each occurrence of —R10a is independently optionally substituted C1-C6aliphatic, halogen, —OR1a, —CN, —NO2, —SR11a, —SO2N(R11a)2, —NR11aSO2R11a, —SO2R11a, —COR11a, —CO2R11a, —N(Ra)2, —CON(R1a)2, —N(R11a)COR11a, —N(R11a)CO2R11a, or —N(R11a)CON(R11a)2;
• each occurrence of —R10b is independently —OR11b, —SR11b, —SO2N(R11b)(R11c), —NR11cSO2R11b, —SO2R11b, —COR11b, —CO2R11b, —N(R11b)(R11c), —CON(R11b)(R11c), —N(R11c)COR11b, —N(R11c)CO2R11b, —N(R11c)CON(R11b)(R11c), or an optionally substituted group selected from a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered saturated, partially unsaturated, or aromatic bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or two occurrences of R11b, taken together with their intervening atom(s), form a spiro, fused, or bridged optionally substituted 5-7-membered saturated, partially unsaturated, or aromatic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• each occurrence of R11a is hydrogen or an optionally substituted C1-C6aliphatic group;
• each occurrence of R11b is an optionally substituted group selected from a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered saturated, partially unsaturated, or aromatic bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• and
• each occurrence of R11c is hydrogen or an optionally substituted group selected from a C1-C6aliphatic group, a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered saturated, partially unsaturated, or aromatic bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or
• R11b and R11c, taken together with the nitrogen atom to which they are bound, form an optionally substituted 3-6-membered saturated, partially unsaturated, or aromatic ring having 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur,
• or a pharmaceutically acceptable salt or composition thereof.

A method of treating a disease, condition, or disorder selected from acute or chronic inflammatory disease, cancer or an osteolytic bone disorder comprising the step of administering to a subject a compound having the formula:

• or a pharmaceutically acceptable salt thereof, wherein:
• x and y are each independently 1 or 2, provided that x and y are not simultaneously 2;
• R1 is fluoro, —R3, —OR4, —SR4, —COOR4, —COR4, —CON(R4)2, —N(R4)2, —SO2N(R4)2, —NR4SO2R3, —NR4COR4, NR4CON(R4)2, —CON(R4)2, —OCOR4, or —OSO2R4;
• R3 is an optionally substituted group selected from C1-C6aliphatic or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• each occurrence of R4 is independently hydrogen or an optionally substituted group selected from C1-C6aliphatic or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two R4 on the same nitrogen atom, taken together with the nitrogen atom, form an optionally substituted 3-6-membered saturated, partially saturated, or aromatic ring having 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• ring A is substituted with q occurrences of RA, wherein q is 0-2 and each occurrence of RA is independently fluoro, —SO2N(RC)2, —ORC, —SRC, —SO2RC, —CORC, —CO2RC, —N(RC)2, —CON(RC)2, —N(RC)CORC, —N(RC)CO2RC, —N(RC)CON(RC)2, or an optionally substituted group selected from C1-C6aliphatic or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two occurrences of RA, or RA and R1, taken together with their intervening atom(s), form an optionally substituted spiro or fused 3-6-membered saturated or partially unsaturated ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein each occurrence of RC is independently hydrogen or an optionally substituted group selected from C1-C6aliphatic or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two occurrences of RC, taken together with the nitrogen atom to which they are bound, form an optionally substituted 3-6-membered saturated, partially unsaturated, or aromatic ring having 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• ring B is substituted with r occurrences of —RB or -L-RB, wherein r is 0-2, L is a C1-4 alkylene and each occurrence of RB is independently fluoro, —ORD, —SRD, CORD, —CO2RD, —N(RD)2, —CON(RD)2, —N(RD)CORD, or an optionally substituted group selected from C1-C6aliphatic or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two occurrences of RB, taken together with their intervening atom(s), form an optionally substituted spiro, fused or bridged 3-6-membered saturated, partially unsaturated, or aromatic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• wherein each occurrence of RD is independently hydrogen or an optionally substituted group selected from C1-C6aliphatic or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two occurrences of RD, taken together with the nitrogen atom to which they are bound, form an optionally substituted 3-6-membered saturated, partially unsaturated, or aromatic ring having 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• n is 1 or 2;
• R2 is -T-Cy2 or -Cy2,
• wherein T, when present, is a C1-C3alkylene chain, wherein the alkylene chain is substituted with 0 or 1 occurrence of R5a, and 0, 1, or 2 independent occurrences of R5b, and wherein one or more methylene units in the C1-C3alkylene chain, as valency and stability permit, is optionally replaced by one or more independent occurrences of-CR5c═CR5c—, —CO—, —SO2—, —O—, —S—, or —NR5c—;
• R5a is halogen, —CN, —OR5c, —N(R5c)2, —SR5c, or an optionally substituted group selected from C1-C6aliphatic, or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• R5b is an optionally substituted group selected from C1-C6aliphatic, or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• R5c is hydrogen, or an optionally substituted group selected from C1-C4aliphatic, or a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two occurrences of R5c, taken together with the nitrogen atom to which they are bound, form an optionally substituted 3-6-membered saturated, partially unsaturated, or aromatic ring having 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• Cy2 is an optionally substituted group selected from a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered partially unsaturated, or aromatic bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• wherein Cy2 is substituted with m independent occurrences of —R6a, -G-R6a, or -V-G-R6a, and k occurrences of ═O, ═S, ═NR7a, ═NR7b, —R6b, -G-R6b, or -V-G-R6b, wherein:
• m is 0-3;
• k is 0-2;
• V is —O—, —N(R7a)—, —S—, —SO—, —SO2—, —SO2N(R7a), —N(R7a)SO2—, —CO—, —CON(R7a)—, —N(R7a)CO—, or —CO2—;
• G is an optionally substituted straight or branched C1-C4alkylene chain that is optionally replaced by —CR7a═CR7a—, —O—, —N(R7a)—, —S—, —SO—, —SO2—, —SO2N(R7a)—, —N(R7a)SO2—, —CO—, —CON(R7a)—, —N(R7a)CO—, or —CO2—, provided that the replacing group is not directly bonded to V, —R6a, or —R6b;
• each occurrence of —R6, is independently optionally substituted C1-C6 aliphatic, halogen, —OR7a, —CN, —NO2, —SR, —SO2N(R7a)2, —NR7aSO2R7b, —SO2R7a, COR7a, CO2R7a N(R7a)2, —N(R7a)COR7a, N(R7a)CO2R7a, or —N(R7a)CON(R7a)2;
• each occurrence of —R6b is independently —OR7b, —SR7b, —SO2N(R7b)(R7c), NR7CSO2R7b, —SO2R7b, —COR7b, —CO2R7b, —N(R7b)(R7c), —CON(R7b)(R7c), —N(R7c)COR7b, —N(R7c)CO2R7b, —N(R7c)CON(R7b)(R7c), or an optionally substituted group selected from a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered saturated, partially unsaturated, or aromatic bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or two occurrences of R6b, taken together with their intervening atom(s), form a spiro, fused, or bridged optionally substituted 5-7-membered saturated, partially unsaturated, or aromatic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• each occurrence of R7a is hydrogen or an optionally substituted C1-C6aliphatic group;
• each occurrence of R7b is an optionally substituted group selected from a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered saturated, partially unsaturated, or aromatic bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• and
• each occurrence of R7c is hydrogen or an optionally substituted group selected from a C1-C6aliphatic group, a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered saturated, partially unsaturated, or aromatic bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or
• R7b and R7c, taken together with the nitrogen atom to which they are bound, form an optionally substituted 3-6-membered saturated, partially unsaturated, or aromatic ring having 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• X is N or CR8,
• wherein R8 is fluoro, —R9, —OR9, —N(R9)2, —SR9, —OCOR9, —COOR9, —CN, —CON(R9)2, —COR9, —SO2R9, —SOR9, —NR9SO2R9, or —SO2N(R9)2, wherein each occurrence of R9 is independently hydrogen or an optionally substituted C1-C6aliphatic group;
• or
• when X is CR8, R8 and R2, taken together with the carbon atom to which they are bound, form an optionally substituted 3-6-membered spiro ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• Q is a C1-C3alkylene chain, wherein the alkylene chain is substituted with 0 or 1 occurrence of R5d, and 0, 1, or 2 independent occurrences of R5, wherein one or more methylene units in the C1-C3alkylene chain, as valency and stability permit, is optionally replaced by one or more independent occurrences of —CR5f═CR5f—, —CO—, —SO2—, —O—, —S—, or —NR51—, wherein R5d is R5a, R5e is R5b, and R5f is R5c;
• Cy1 is an optionally substituted group selected from a 5-8-membered partially unsaturated or aromatic unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-14-membered partially unsaturated or aromatic bicyclic or tricyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• wherein Cy1 is substituted with p independent occurrences of —R10a, -J-R10a, or
• W-J-R10a, and j occurrences of ═O, ═S, ═NR11a, ═NR11b, —R10b, -J-R10b, or —W-J-R10b, wherein:
• p is 0-3;
• j is 0-2;
• W is —O—, —N(R11a)—, —S—, —SO—, —SO2—, —SO2N(R11a)—, —N(R11a)SO2—, —CO—, —CON(R11a)—, —N(R11a)CO—, or —CO2—;
• J is an optionally substituted straight or branched C1-C4alkylene chain that is optionally replaced by —CR11a═CR11a—, —O—, —N(R11a)—, —S—, —SO—, —SO2—, —SO2N(R11a)—, —N(R11a)SO2—, —CO—, —CON(R11a)—, —N(R11a)CO—, or —CO2—, provided that the replacing group is not directly bonded to W, —R10a, or —R10b;
• each occurrence of —R10b is independently optionally substituted C1-C6 aliphatic, halogen, —OR11a, —CN, —NO2, —SR11a, —SO2N(R11a)2, —NR11aSO2R11a, —SO2R11a, —COR11a, —CO2R11a, —N(R11c)2, —CON(R11a)2, —N(R11a)COR11a, —N(R11a)CO2R11a, or —N(R11a)CON(R11a)2;
• each occurrence of —R10b is independently —OR11b, —SR11b, —SO2N(R11b)(R11c), —NR11cSO2R11b, —SO2R11b, —COR11b, —CO2R11b, —N(R11b)(R11c), —CON(R11b)(R11c), —N(R11c)COR11b, —N(R11c)CO2R11b, —N(R11c)CON(R11b)(R11c), or an optionally substituted group selected from a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered saturated, partially unsaturated, or aromatic bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or two occurrences of R10b, taken together with their intervening atom(s), form a spiro, fused, or bridged optionally substituted 5-7-membered saturated, partially unsaturated, or aromatic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• each occurrence of R11a is hydrogen or an optionally substituted C1-C6aliphatic group;
• each occurrence of R11b is an optionally substituted group selected from a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered saturated, partially unsaturated, or aromatic bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• and
• each occurrence of R11c is hydrogen or an optionally substituted group selected from a C1-C6aliphatic group, a 3-7-membered saturated, partially unsaturated, or aromatic monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10-membered saturated, partially unsaturated, or aromatic bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or
• R11b and R11c, taken together with the nitrogen atom to which they are bound, form an optionally substituted 3-6-membered saturated, partially unsaturated, or aromatic ring having 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur,
• or a pharmaceutically acceptable salt or composition thereof.