Pyrazine derivatives as enac blockers

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein
• R1 is H, halogen, C1-C8-alkyl, C1-C8-haloalkyl, C1-C8-haloalkoxy, C3-C15-carbocyclic group, nitro, cyano, a C6-C15-membered aromatic carbocyclic group, or a C1-C8-alkyl substituted by a C6-C15-membered aromatic carbocyclic group;
• R2, R3, R4 and R5 are each independently selected from H and C1-C6 alkyl;
• R6, R7, R8 and R9 are each independently selected from H;
• SO2R16;
• aryl optionally substituted by one or more Z groups;
• a C3-C10 carbocyclic group optionally substituted by one or more Z groups;
• C3-C14 heterocyclic group optionally substituted by one or more Z groups;
• C1-C8 alkyl optionally substituted by an aryl group which is optionally substituted by one or more Z groups, a C3-C10 carbocyclic group optionally substituted by one or more Z groups or a C3-C14 heterocyclic group optionally substituted by one or more Z groups;
• R10 is represented by the formula 2:
• —(C0-C3alkylene)-B—X—(CR11aR12a)m—(CR11bR12b)n—(CR11cR12c)p—C(O)OR13,
• wherein the alkylene groups are optionally substituted by one or more Z groups;
• B is aryl optionally substituted by one or more Z groups;
• X is selected from a bond, —NR15(SO2)—, —(SO2)NR15—, —(SO2)—, —NR15C(O)—, —C(O)NR15—, —NR15C(O)NR17—, —NR15C(O)O—, —NR15—, C(O)O, OC(O), C(O), O and S;
• R11a, R11b, R11c, R12a, R12b and R12c are each independently selected from H and C1-C6 alkyl;
• or
• R11a and R12a together with the carbon atom to which they are attached form a 3- to 8-membered cycloalkyl group;
• or
• R11b and R12b together with the carbon atom to which they are attached form a 3- to 8-membered cycloalkyl group;
• or
• R11c and R12c together with the carbon atom to which they are attached form a 3- to 8-membered cycloalkyl group;
• R13 is selected from (C1-C3 alkyl)-C(O)NR22R23;
• (C1-C3 alkyl)-C(O)OR23;
• and (C1-C3 alkyl)-NR23C(O)R22
• R15 and R17 are each independently selected from H and C1-C6 alkyl;
• R16 is selected from C1-C8 alkyl, aryl and a 3- to 14-membered heterocyclic group, the heterocyclic group including one or more heteroatoms selected from N, O and S;
• Z is independently selected from —OH, aryl, —O-aryl, C7-C14 aralkyl, —O—C7-C14 aralkyl, C1-C6 alkyl, C1-C6 alkoxy, —NR19(SO2)R21, —(SO2)NR19R21, —(SO2)R20, —NR19C(O)R20, —C(O)NR19R20, —NR19C(O)NR20R18, —NR19C(O)OR20, —NR19R21, C(O)OR19, —C(O)R19, SR19, —OR19, oxo, CN, NO2, and halogen, wherein the alkyl, alkoxy, aralkyl and aryl groups are each optionally substituted by one or more substituents selected from OH, halogen, C1-C4 haloalkyl and C1-C4 alkoxy;
• R18, R20 and R22 are each independently selected from H and C1-C6 alkyl;
• R19, R21 and R23 are each independently selected from H;
• C1-C8 alkyl;
• C3-C8 cycloalkyl;
• C1-C4 alkoxy-C1-C4 alkyl;
• (C0-C4 alkyl)-aryl optionally substituted by one or more groups selected from C1-C6 alkyl, C1-C6 alkoxy and halogen;
• (C0-C4 alkyl)-3- to 14-membered heterocyclic group, the heterocyclic group including one or more heteroatoms selected from N, O and S, optionally substituted by one or more groups selected from halogen, oxo, C1-C6 alkyl and —C(O)C1-C6 alkyl;
• —(C0-C4 alkyl)-O-aryl optionally substituted by one or more groups selected from C1-C6 alkyl, C1-C6 alkoxy and halogen;
• and (C0-C4 alkyl)-O-3- to 14-membered heterocyclic group, the heterocyclic group including one or more heteroatoms selected from N, O and S, optionally substituted by one or more groups selected from halogen, C1-C6 alkyl and —C(O)C1-C6 alkyl;
• wherein the alkyl groups are optionally substituted by one or more halogen atoms, hydroxyl, C1-C4 alkoxy, —C(O)NH2, —C(O)NHC1-C6 alkyl or —C(O)N(C1-C6 alkyl)2;
• or
• R19 and R20 together with the nitrogen atom to which they are attached form a 5- to 10-membered heterocyclic group, the heterocyclic group including one or more further heteroatoms selected from N, O and S, the heterocyclic group being optionally substituted by one or more substituents selected from OH;
• halogen;
• aryl;
• 5- to 10-membered heterocyclic group including one or more heteroatoms selected from N, O and S;
• —S(O)2-aryl;
• —S(O)2—C1-C6 alkyl;
• C1-C6 alkyl optionally substituted by one or more halogen atoms;
• C1-C6 alkoxy optionally substituted by one or more OH groups or C1-C4 alkoxy;
• and C(O)OC1-C6 alkyl, wherein the aryl and heterocyclic substituent groups are themselves optionally substituted by C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy;
• or
• R19 and R21 together with the nitrogen atom to which they are attached form a 5- to 10-membered heterocyclic group, the heterocyclic group including one or more further heteroatoms selected from N, O and S, the heterocyclic group being optionally substituted by one or more substituents selected from OH;
• halogen;
• aryl;
• 5- to 10-membered heterocyclic group including one or more heteroatoms selected from N, O and S;
• —S(O)2-aryl;
• —S(O)2—C1-C6 alkyl;
• C1-C6 alkyl optionally substituted by one or more halogen atoms;
• C1-C6 alkoxy optionally substituted by one or more OH groups or C1-C4 alkoxy;
• and —C(O)OC1-C6 alkyl, wherein the aryl and heterocyclic substituent groups are themselves optionally substituted by C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy;
• or
• R18 and R20 together with the nitrogen atom to which they are attached form a 5- to 10-membered heterocyclic group, the heterocyclic group including one or more further heteroatoms selected from N, O and S, the heterocyclic group being optionally substituted by one or more substituents selected from OH;
• halogen;
• aryl;
• 5- to 10-membered heterocyclic group including one or more heteroatoms selected from N, O and S;
• —S(O)2-aryl;
• —S(O)2—C1-C6 alkyl;
• C1-C6 alkyl optionally substituted by one or more halogen atoms;
• C1-C6 alkoxy optionally substituted by one or more OH groups or C1-C4 alkoxy;
• and —C(O)OC1-C6 alkyl, wherein the aryl and heterocyclic substituent groups are themselves optionally substituted by C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy;
• or
• R22 and R23 together with the atom(s) to which they are attached form a 5- to 10-membered heterocyclic group, the heterocyclic group including one or more further heteroatoms selected from N, O and S, the heterocyclic group being optionally substituted by one or more Z groups;
• m is 0, 1, 2 or 3;
• n is 0, 1, 2 or 3;
• p is 0, 1, 2 or 3;
• wherein at least one of m, n or p is not 0.