Small-molecule inhibitors of interleukin-2

A compound of formula I

• where:
• m is an integer selected from 0, 1, and 2;
• n and o are integers independently selected from 0 and 1;
• A is selected from the group consisting of N and CH;
• B is selected from the group consisting of —CH2—CH2—, —CH2—CH2—CH2—, —CH2—CH2—NH—, —CH2—O—CH2—, —CH2—S—CH2—, —C(═O)—NH—, —C(═O)—CH2—, —CH2—C(═O)—NH—, —C(═O)—CH2—C(═O)—, —C(═O)—NH—CH2—, —C(═O)—, —S(═O)—, —S(═O)2—, —S(═O)—NH—, —S(═O)2—NH—, —S(═O)—CH2—, —S(═O)2CH2—, —S(═O)—CH2—NH—, —S(═O)2—CH2—NH—, —S(═O)2—NH—CH2—, —CH2—S(═O)2—NH—, —C(═O)—NH—S(═O)2—, —S(═O)2—NH—C(═O)—, —C(═O)—CH2—S(═O)2—, and —S(═O)2—CH2—C(═O)—;
• J is absent or selected from the group consisting of —O—, —S—, —CHR15—O—, —CH2—CHR15—O—, —NH—, —NH—CHR15—, —NH—CHR15—C(═O)—, —C(═O)—, —CH2—, —CHR15—CH2—NH—, —C(═O)—CHR15—, —NH—C(═O)—CH(C1-C6alkyl)-, —NH—C(═O)—CH(C3-C12cycloalkyl)-, —CH2CH2—, —CH2NH—, —CH2—NH—C(═O)—, —CH2—NH—C(═O)—C1-C6alkyl-, —CH2—NH—C(═O)—CH(C3-C12cycloalkyl)- and —C(═O)—CHR15—NH—;
• or
• B—J is selected from the group consisting of —C(═O)—CH2—NH—C(═O)—CH(C1-C6alkyl), —C(═O)—CH2—NH—C(═O)—CH(C3-C12cycloalkyl)-, —C(═O)—NH—(C2-C6alkyl), —S(═O)2—NH—(C2-C6alkyl)-, —C(═O)—NH—, —S(═O)2—NH—, —C(═O)—CH2— and —S(═O)2—CH2—;
• L is selected from the group consisting of —O—, —CH2—O—, —O—CH2—, —CH2—CH2—O—, —O—CH2—CH2—, —CH2—O—CH2—, —CH2—S—CH2—, —C(═O)—NH—, —O—C(═O)—NH—, —CH2—C(═O)—NH—, —C(═O)—CH2—NH—, —C(═O)—NH—CH2—, —NH—C(═O)—, NH—C(═O)—O—, —NH—CH2—C(═O)—, —NH—C(═O)—CH2—, —CH2—NH—C(═O)—, —NH—C(═O)—NH—, —NH—S(═O)2—NH—, —NH—S(═O)2—, —NH—S(═O)2—CH2—, —CH2—NH—S(═O)2—, —S(═O)2—NH—, —S(═O)2—NH—CH2—, —CH2—S(═O)2—NH—, —C(═O)—NH—S(═O)2—, —S(═O)2—NH—C(═O)—, —CH2—NH—, —CH2—CH2—NH—, —NH—CH2—, —NH—CH2—CH2—, —CH2—NH—CH2—, —C≡C—, —CH2—C≡C—, —CH2—CH2—, —CH2—CH2—CH2—, —CH2—CH═CH—, CH═CH—CH2—, and —CH═CH—;
• M is selected from the group consisting of R9,
• Q is selected from the group consisting of —C(═O)OR16, —C(═O)—NH—C(═O)—CF3, —C(═O)—NH—S(═O)2—R2, —C(═O)—NR1—OH, 5-oxo-4,5-dihydro[1,2,4]oxadiazol-3-yl, and tetrazolyl;
• X is A when n is 1, and is CH, N, O or S when n is 0;
• R1 is selected from the group consisting of hydrogen, (C1-C6)alkyl, halo-(C1-C6)alkyl, and (C3-C6)cycloalkyl;
• R2, R3 and R5 are individually selected from the group consisting of hydrogen, cyano, nitro, phenyl, phenoxy, benzyl, C1-C6alkyl, halo, halo-C1-C6alkyl, C3-C6cycloalkyl, C1-C6alkoxy, hydroxy, C1-C2alkoxy-methoxy, hydroxy-C1-C6alkyl, formyl, C1-C6alkylcarbonyl, amino, C1-C6alkylamino, aminocarbonyl, C1-C6alkylaminocarbonyl, formylamino, and C1-C6alkylcarbonylamino, where any alkyl or phenyl may optionally be substituted with halo or Q;
• R4 is selected from the group consisting of R2 and
• where Ar is a homo- or hetero-aryl group having 1 or 2 rings, each ring containing 5,6 or 7 ring atoms of which 1-3 may be heteroatoms selected from N, O and S;
• R6 is selected from the group consisting of hydrogen, C1-C6alkyl, halo, halo-C1-C6alkyl, C3-C6cycloalkyl, C1-C6alkoxy, C1-C6alkoxy-C1-C6alkyl, hydroxy, hydroxy-C1-C6alkyl, HC(═O)—C1-C6alkyl, carboxy, carboxy-C1-C6alkyl, carbonylamino-C1-C6alkyl, aminocarbonyl, (C1-C6alkyl)aminocarbonyl, di(C1-C6alkyl)aminocarbonyl, and aminocarbonyl-C1-C6alkyl;
• R7 is selected from the group consisting of hydrogen, C1-C6 alkyl, halo, halo-C1-C6alkyl, C3-C6cycloalkyl, C1-C6alkoxy, C1-C6alkoxy-C1-C6alkyl, hydroxy, hydroxy-C1-C6alkyl, HC(═O)—C1-C6alkyl, carboxy, carboxy-C1-C6alkyl, carbonylamino-C1-C6alkyl, aminocarbonyl, (C1-C6alkyl)aminocarbonyl, di(C1-C6alkyl)aminocarbonyl, and aminocarbonyl-C1-C6alkyl;
• R7′ is hydrogen;
• or
• R7 and R7′ together with the carbon to which they are bonded form —C(═O)—;
• R8 selected from the group consisting of hydrogen, hydroxy, C1-C6alkoxy, C1-C6alkyl, halo, halo-C1-C6alkyl, and C3-C6cycloalkyl;
• R9 is selected from the group consisting of —NR10R11, —C(═NR12)—NHR13, —N═CR14—NR10R11, —NR13—CR14═NR12, and —NR13—C(═NR12)—NHR13;
• R10, R11, R12, R13 and R14 are independently selected from the group consisting of hydrogen, hydroxy, hydroxy-C1-C6alkyl, C1-C6alkyl, halo-C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxy-C1-C6alkyl, and C3-C7 cycloalkyl;
• or any member of the group R10, R11, R12, R13 together with the nitrogen to which it is attached forms a 5, 6 or 7 member heterocycle with any other member of the group, the heterocycle optionally containing one additional heteroatom selected from N, O and S;
• R15 is selected from the group consisting of hydrogen, C1-C12alkyl, C3-C7cycloalkyl, aminocarbonyl, C1-C6alkylaminocarbonyl, and di(C1-C6alkyl)aminocarbonyl;
• and
• R16 is selected from the group consisting of hydrogen, C1-C6alkyl, C3-C13cycloalkyl, C6-C10aryl, acetylamino-C1-C12alkyl, C1-C6alkylcarbonyloxy-C1-C6alkyl, and C6-C10aryl-C0-C6alkylcarbonyloxy-C1-C6alkyl,
• or a pharmaceutically acceptable salt thereof.