Immunomodulators

A compound of formula (I)

• or a pharmaceutically acceptable salt thereof, wherein:
• A is selected from
• wherein:
• denotes the point of attachment to the carbonyl group and denotes the point of attachment to the nitrogen atom;
• n is 0 or 1;
• m is 1 or 2;
• u is 0 or 1;
• w is 0, 1, or 2;
• Rx is selected from hydrogen, amino, hydroxy, and methyl;
• R14 and R11 are independently selected from hydrogen and methyl;
• R16a is selected from hydrogen and C1-C6 alkyl;
• R16 is selected from
• —(C(R17a)2)2—X—R30, —(C(R17aR17))0-2—X′—R30, —(C(R17aR17)1-2C(O)NR16a)m′—X′—R30,
• —C(R17a)2C(O)N(R16a)C(R17a)2—X′—R31, —(C(R17aR17))12C(O)N(R16a)C(R17a)2—X′—R31,
• —C(R17a)2[C(O)N(R16a)C(R17a)2]w′—X—R31, —C(R17aR17)1-2[C(O)N(R16a)C(R17aR17)1-2]w′—X′—R31,
• —(C(R17a)(R17)C(O)NR16a)n′—H;
• and
• —(C(R17a)(R17)C(O)NR16a)m′—C(R17a)(R17)—CO2H;
• wherein a PEGq′ spacer can be inserted in any part of the R16 (q′ is the number of —(CH2CH2O)— unit in a PEG spacer);
• wherein w′ is 2 or 3;
• n′ is 1-6;
• m′ is 0-5;
• q′ is 1-20
• X is a chain of between 1 and 172 atoms wherein the atoms are selected from n:
• carbon and oxygen and wherein the chain may contain one, two, three, or four groups selected from —NHC(O)—, —NHC(O)NH—, and —C(O)NH— embedded therein;
• and wherein the chain is optionally substituted with one to six groups independently selected from —CO2H, —C(O)NH2, —CH2C(O)NH2, and —(CH2)1-2CO2H;
• X′ is a chain of between 1 and 172 atoms wherein the atoms are selected from carbon and oxygen and wherein the chain may contain one, two, three, or four groups selected from —NHC(O)—, —NHC(O)NH—, and —C(O)NH— embedded therein;
• and wherein the chain is optionally substituted with one to six groups independently selected from —CO2H, —C(O)NH2, and —(CH2)1-2CO2H, provided that X′ is other than unsubstituted PEG;
• R30 is selected from —SO3H, —S(O)OH, and —P(O)(OH)2;
• R31 is selected from —S(O)2OH, —S(O)OH, and —P(O)(OH)2;
• each R17a is independently selected from hydrogen, C1-C6alkyl, —CH2OH, —CH2CO2H, —(CH2)2CO2H,
• each R17 is independently selected from hydrogen, —CH3, (CH2)zN3,
• —(CH2)zNH2, —X—R31, —(CH2)zCO2H, —CH2OH, CH2C≡CH, and —(CH2)z-triazolyl-X—R35, wherein z is 1-6 and R35 is selected from —SO3H, —S(O)OH, and —P(O)(OH)2;
• provided at least one R17 is other than hydrogen, —CH3, or —CH2OH;
• provided at least one of R30, R31, or R35 is present;
• Ra, Re, Rj, and Rk, are each independently selected from hydrogen and methyl;
• R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are independently selected from a natural amino acid side chain and an unnatural amino acid side chain or form a ring with the corresponding vicinal R group as described below;
• Rb is methyl or, Rb and R2, together with the atoms to which they are attached, form a ring selected from azetidine, pyrrolidine, morpholine, piperidine, piperazine, and tetrahydrothiazole;
• wherein each ring is optionally substituted with one to four groups independently selected from amino, cyano, methyl, halo, and hydroxy;
• Rd is hydrogen or methyl, or, Rd and R4, together with the atoms to which they are attached, can form a ring selected from azetidine, pyrrolidine, morpholine, piperidine, piperazine, and tetrahydrothiazole;
• wherein each ring is optionally substituted with one to four groups independently selected from amino, cyano, methyl, halo, hydroxy, and phenyl;
• R9 is hydrogen or methyl or R9 and R7, together with the atoms to which they are attached, can form a ring selected from azetidine, pyrrolidine, morpholine, piperidine, piperazine, and tetrahydrothiazole;
• wherein each ring is optionally substituted with one to four groups independently selected from amino, benzyl optionally substituted with a halo group, benzyloxy, cyano, cyclohexyl, methyl, halo, hydroxy, isoquinolinyloxy optionally substituted with a methoxy group, quinolinyloxy optionally substituted with a halo group, and tetrazolyl;
• and wherein the pyrrolidine and the piperidine ring are optionally fused to a cyclohexyl, phenyl, or indole group;
• and
• R1 is methyl or, R1 and R12, together with the atoms to which they are attached, form a ring selected from azetidine and pyrrolidine, wherein each ring is optionally substituted with one to four independently selected from amino, cyano, methyl, halo, and hydroxy.