Sodium channel inhibitors

A compound having Formula (II):

• or a pharmaceutically acceptable salt or solvate thereof;
• Z is selected from the group consisting of 5-membered heteroaryl having from 1 to 4 heteroatoms as ring members selected from N, O or S and 6-membered heteroaryl having from 1 to 3 nitrogen heteroatoms as ring members;
• Y is selected from the group consisting of 5-membered heteroaryl having from 1 to 4 heteroatoms as ring members selected from N, O or S, 6-membered heteroaryl having from 1 to 3 nitrogen heteroatoms as ring members, and aryl optionally fused with a 5-membered heteroaryl having 1 to 2 heteroatoms as ring members selected from O, N or S;
• or Y and X1 are taken together to form a 5-membered fused heteroaryl ring having from 0-2 additional nitrogen atoms as ring members and R1 is a lone pair, wherein the fused heteroaryl ring is optionally substituted with a Rb group;
• wherein the heteroaryl and aryl of Y and Z substituents are each optionally substituted with from 1 to 3 Ra substituents, at each occurrence, each Ra is independently selected from the group consisting of C1-8alkyl-NH—, (C1-8alkyl)2N—, aryl, Rb, C1-8haloalkyl, aryl-C3-8cycloalkyl, C3-8cycloalkyl, heterocycloalkyl, arylsulfonyl, arylsulfinyl and Rf, wherein Rb is C1-8alkyl optionally substituted with from 1-3 members independently selected from the group consisting of aryl, aryl-C(O)—, aryloxy, (Rc)(Rd)N—, C3-5cycloalkyl, hetero-C4-5cycloalkyl, arylthio and heteroaryl;
• wherein Rc is —H or C1-6alkyl and Rd is C3-7cycloalkyl or C1-8alkyl optionally substituted with from 1-2 aryl groups, or optionally Rc and Rd together with the nitrogen atom to which they are attached form a 5 or 6-membered ring having 0-2 additional heteroatoms as ring members selected from N, O or S;
• wherein the aryl portion of each Ra substituent is further optionally substituted with from 1-3 substituents independently selected from the group consisting of C1-4haloalkyl, C1-4haloalkoxy and Rf, and the heterocycloalkyl of the Rb group is further optionally substituted with a hetero-C4-5cycloalkyl-C1-6alkyl;
• or any two adjacent Ra substituents together with the atoms to which they are attached form a 5- or 6-membered carbocyclic ring, wherein 1-2 ring carbon atoms of the carbocyclic ring are optionally replaced by a carbonyl and the carbocyclic ring is optionally substituted with 1-2 members independently selected from an halogen, aryl or C1-8alkyl;
• wherein Rf is halogen, —OH, —ORg, —OC(O)O—Rg, —OC(O)Rg, —OC(O)NHRg, —OC(O)N(Rg)2, —SH, —SRg, —S(O)Rg, —S(O)2Rg, —SO2NH2, —S(O)2NHRg, —S(O)2N(Rg)2, —NHS(O)2Rg, —NRgS(O)2Rg, —C(O)NH2, —C(O)NHRg, —C(O)N(Rg)2, —C(O)Rg, —C(O)H, —C(═S)Rg, —NHC(O)Rg, —NRgC(O)Rg, —NHC(O)NH2, —NRgC(O)NH2, —NRgC(O)NHRg, —NHC(O)NHRg, —NRgC(O)N(Rg)2, —NHC(O)N(Rg)2, —CO2H, —CO2Rg, —NHCO2Rg, —NRgCO2Rg, —CN, —NO2, —NH2, —NRgS(O)NH2, —NRgS(O)2NHRg, —NHC(═NRg)NH2, —N═C(NH2)NH2, —C(═NRg)NH2, —NH—OH, —NRg—OH, —NRg—ORg, —N═C═O and —N═C═S;
• wherein each Rg is independently a C1-8alkyl;
• X1, X2, X3 and X4 are each independently —N═, or C(R2)═, wherein R2 is selected from the group consisting of —H, halogen, —OH, C1-8alkyl, —CN, C1-6haloalkyl and C1-6haloalkoxy;
• or any two adjacent R2 substituents together with the atoms to which they are attached form a fused benzene ring, optionally substituted with a C1-6alkyl, with the proviso that not more than three of X1, X2, X3 and X4 are —N═;
• L is a bond or
• i) L, the aromatic carbon atom to which L is attached, and X1 taken together form a fused 5- or 6-membered carbocyclic ring, wherein 1-2 ring carbon atoms of the fused carbocyclic ring are optionally replaced with —C(O)— or —S(O)2— group;
• or
• ii) L, the two atoms to which L is attached, and X1 taken together form a 5- or 6-membered fused heterocyclic ring having from 0-2 additional heteroatoms selected from N, O or S, wherein 1-2 ring carbon atoms of the fused heterocyclic ring are optionally replaced with —C(O)— or —S(O)2— group;
• R1 is —H, a lone pair or C1-8alkyl;
• with the proviso that the compound is other than 4-(4-methylphthalazin-1-ylamino)-N-(thiazol-2-yl)benzenesulfonamide;
• 4-(4-(4-chlorophenyl)phthalazin-1-ylamino)-N-(thiazol-2-yl)benzenesulfonamide;
• N-(thiazol-2-yl)-4-(4-p-tolylphthalazin-1-ylamino)benzenesulfonamide;
• and 4-(4-phenylphthalazin-1-ylamino)-N-(thiazol-2-yl)benzenesulfonamide;
• and
• at each occurrence, “alkyl” by itself or as part of another substituent, is an unsubstituted, fully saturated, straight or branched chain hydrocarbon radical;
• at each occurrence, “cycloalkyl” by itself or as part of another substituent is an unsubstituted, fully saturated, cyclic hydrocarbon radical;
• and
• at each occurrence, “aryl” by itself or as part of another substituent is a monovalent monocyclic, bicyclic or polycyclic polyunsaturated aromatic hydrocarbon radical.