2,3,5-trisubstituted thiophene compounds and uses thereof

A compound of formula (I):

• or a salt thereof, wherein
• m is 0, 1 or 2;
• n is 0 or 1, wherein m+n is 1, 2 or 3;
• R1 is C3-C10alkynyl or phenyl, which phenyl is substituted with 0, 1, 2, or 3 substituents which are independently selected from the group consisting of halogen, hydroxy, cyano, C1-C4alkyl, haloC1-C4alkyl and C1-C4alkoxy, and which alkynyl is optionally substituted with a C3-C7cycloalkyl substituent, which cycloalkyl is optionally substituted with 1 or 2 independently selected C1-C4alkyl groups;
• R2 is CO2H or C(O)N(H)S(O)2CH3;
• R3 is C3-C7cycloalkyl which is substituted with 0, 1, 2 or 3 halogen atoms;
• R3a represents 0, 1, 2, 3 or 4 residues independently selected at each occurrence from the group consisting of hydroxy, amino, cyano, halogen, C1-C6alkyl, and C1-C6alkoxy, wherein each alkyl or alkoxy substituent is substituted with 0, 1 or 2 substituents independently selected from hydroxy, cyano, C1-C4alkoxy, C1-C4alkylsulfone, N(R3b)2, C(O)N(R3b), heterocycle having 4 to 7 ring atoms and 1 or 2 ring heteroatoms selected from N, O and S and 5 or 6 member heteroaryl;
• or two geminal R3a substituents, taken in combination form a spirocyclic 3 to 6 member cycloalkyl or heterocycle;
• R3b is independently selected at each occurrence from hydrogen, C1-C4alkyl, C1-C4alkoxyC1-C4alkyl and C1-C4alkanoyl;
• or N(R3b)2, taken in combination, form a 4 to 6 member heterocycle having 0 or 1 additional ring heteroatoms selected from N, O and S;
• X is O, N-L-R4 or CR5R6;
• L is a bond, S(O)2 or C(O);
• R4 is C1-C6alkyl or C3-C7cycloalkyl each of which is substituted with 0, 1, or 2 hydroxy and 0 or 1 substituents selected from cyano, S(O)2—C1-C4alkyl, CO2H or NR4aR4b or phenyl;
• R4 is naphthyl or phenyl, which phenyl is substituted with 0, 1, 2, or 3 substituents independently selected form the group consisting of halogen, cyano, C1-C6alkyl, haloC1-C6alkyl, C1-C6alkoxy, haloC1-C6alkoxy, amino, hydroxy, mono- and di-C1-C6alkylamino, hydroxyC1-C4alkyl, aminoC1-C4alkyl, C1-C6alkyl-OC(O)NH—, C1-C4alkyl-C(O)NH—, —C(O)NR4aR4b, phenyl, phenoxy, heteroaryl having one or two ring nitrogen atoms and having 0, 1, or 2 C1-C4alkyl substituents, or two substituents combine to form a fused heterocyclic ring, which heterocycle has 5, 6 or 7 ring atoms, 1 or 2 ring heteroatoms selected from N, O and S and which heterocycle is substituted with 0, 1 or 2 substituents independently selected from C1-C6alkyl;
• or
• R4 is a 5 or 6 member heteroaryl having 1 to 3 heteroatoms selected from N, O and S, which heteroaryl is substituted with 0, 1, or 2 substituents independently selected from the group consisting of halogen, cyano, C1-C6alkyl, haloC1-C6alkyl, C1-C6alkoxy, haloC1-C6alkoxy, hydroxy, NR4aR4b, hydroxyC1-C4alkyl, aminoC1-C4alkyl, C1-C6alkyl-OC(O)NH—, C3-C7cycloalkyl, C5-C7cycloalkenyl, phenyl, 5 or 6 membered heteroaryl having 1 or 2 ring heteroatoms selected from N, O and S, and saturated or partially unsaturated monocyclic or bicyclic heterocycle which heterocycle has 1 or 2 ring N, O or S atoms, 5 to 7 ring atoms in each ring and is substituted with 0, 1 or 2 substituents independently selected from the group consisting of halogen, C1-C6alkyl, C1-C6alkanoyl, C1-C6alkoxyC(O)N(H)CH2, aminoC1-C4alkyl, C1-C4alkoxyC1-C4alkyl and NR4aR4b, and wherein the phenyl or heteroaryl substituent is unsubstituted or substituted with 1 or 2 independently selected substituents selected from halogen, CO2H, cyano, C1-C4alkyl, C1-C4alkoxy, CH2NR4aR4b and C(O)NR4aR4b;
• or
• R4 is a saturated heterocycle having 1 ring nitrogen and 0 or 1 additional ring heteroatom selected from N, O and S, which heterocyclic ring is substituted with 0, 1, or 2 substituents independently selected from the group consisting of C1-C6alkyl, CO2C1-C6alkyl and CO2-benzyl;
• R4a is independently selected at each occurrence from the group consisting of hydrogen and C1-C6alkyl, wherein the alkyl substituent is unsubstituted or substituted with hydroxy, C1-C4alkoxy, amino or mono- and di-C1-C4alkylamino;
• R4b is independently selected at each occurrence from the group consisting of hydrogen, C1-C6alkyl and C1-C4alkanoyl, wherein the alkyl substituent is unsubstituted or substituted with hydroxy, C1-C4alkoxy, amino or mono- and di-C1-C4alkylamino;
• or
• NR4aR4b, taken in combination, form a heterocyclic ring having one ring nitrogen atom and 0 or 1 additional ring heteroatom selected from N, O and S, which heterocyclic ring is substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of halogen, hydroxy, amino, C1-C4alkyl, haloC1-C4alkyl, hydroxyC1-C4alkyl, aminoC1-C4alkyl, C1-C4alkoxy, C1-C4alkoxyC1-C4alkyl, and mono- and di-C1-C4alkylamino;
• R5 is absent or is selected from the group consisting of hydrogen and C1-C6alkyl;
• R6 is oxo, hydrogen, hydroxy, amino, N(H)-J-R7;
• J is absent, C(O) or S(O)2;
• and
• R7 is C1-C6alkyl, phenyl or benzyl, each of is optionally substituted with C1-C6alkyl, C1-C6alkoxy, halogen, phenyl or phenoxy.