Biphenyl derivatives as modulators of voltage gated ion channels

A compound of formula I:

• or a pharmaceutically acceptable salt thereof;
• wherein:
• ring Z is a 5 [-7] membered unsaturated or aromatic ring having at least one ring heteroatom selected from O, S, N, and NH, wherein Z is optionally substituted with up to z occurrence of RZ;
• z is 0 to 4;
• each RZ is independently selected from R1, R2, R3, R4, and R5;
• the SO2 group is attached to either carbon no. 1 or 2;
• the NRM—C(O)-Q-RQ is attached to either carbon no. 3′ or 4′;
• wherein the phenyl ring containing carbon no. 3′ is optionally substituted with up to 4 substituents selected from halo, CN, NO2, CF3, OCF3, OR6, SR6, S(O)R2, SO2R2, NH2, N(R2)2, COOR2, and C1-C6 straight or branched alkylidine chain, wherein up to two non-adjacent methylene units of said alkylidine are optionally and independently replaced by —CO—, —CS—, —COCO—, —CONR2—, —CONR2NR2—, —CO2—, —OCO—, —NR2CO2—, —O—, —NR2CONR2—, —OCONR2—, —NR2NR2—, —NR2NR2CO—, —NR2CO—, —S—, —SO—, —SO2—, —NR2—, —SO2NR2—, NR2SO2—, or —NR2SO2NR2—;
• Q is a bond or is a C1-C6 straight or branched alkylidine chain, wherein up to two non-ajacent methylene units of Q are optionally and independently replaced by —CO—, —CS—, —COCO—, —CONR2—, —CONR2NR2—, —CO2—, —OCO—, —NR2CO2—, —O—, —NR2CONR2, —OCONR2—, —NR2NR2—, —NR2NR2CO—, —NR2CO—, —S—, —SO—, —SO2—, —NR2—, —SO2NR2—, NR2SO2—, —NR2SO2NR2—, or a spirocycloalkylene moeity;
• RQ is a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from O, S, N, and NH, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from O, S, N, and NH;
• wherein RQ is optionally substituted with up to 4 substituents selected from R1, R2, R3, R4, and R5;
• each of RN and RM is independently R2;
• R1 is oxo, ═NN(R6)2, ═NN(R7)2, ═NN(R6R7), R6 or (CH2)n—Y;
• n is 0, 1 or 2;
• Y is halo, CN, NO2, CF3, OCF3, OH, SR6, S(O)R6, SO2R6, NH2, NHR6, N(R6)2, NR6R8, COOH, COOR6, or OR6;
• or two R1 on adjacent ring atoms, taken together, form 1,2-methylenedioxy or 1,2-ethylenedioxy;
• R2 is hydrogen or C1-C6 aliphatic, wherein each R2 is optionally substituted with up to 2 substituents independently selected from R1, R4, and R5;
• R3 is a C3-C8 cycloaliphatic, C6-C10 aryl, C3-C8 heterocyclic, or C5-C10 heteroaryl ring, optionally substituted with up to 3 substituents, independently selected from R1, R2, R4, and R5;
• R4 is OR5, OR6, OC(O)R6, OC(O)R5, OC(O)OR6, OC(O)OR5, OC(O)N(R6)2, OC(O)N(R5)2, OC(O)N(R6R5), OP(O)(OR6)2, OP(O)(OR5)2, OP(O)(OR6)(OR5), SR6, SR5, S(O)R6, S(O)R5, SO2R6, SO2R5, SO2N(R6)2, SO2N(R5)2, SO2NR5R6, SO3R6, SO3R5, C(O)R5, C(O)OR5, C(O)R6, C(O)OR6, C(O)N(R6)2, C(O)N(R5)2, C(O)N(R5R6), C(O)N(OR6)R6, C(O)N(OR5)R6, C(O)N(OR6)R5, C(O)N(OR5)R5, C(NOR6)R6, C(NOR6)R5, C(NOR5)R6, C(NOR5)R5, N(R6)2, N(R5)2, N(R5R6), NR5C(O)R5, NR6C(O)R6, NR6C(O)R5, NR6C(O)OR6, NR5C(O)OR6, NR6C(O)OR5, NR5C(O)OR5, NR6C(O)N(R6)2, NR6C(O)NR5R6, NR6C(O)N(R5)2, NR5C(O)N(R6)2, NR5C(O)NR5R6, NR5C(O)N(R5)2, NR6SO2R6, NR6SO2R5, NR5SO2R5, NR6SO2N(R6)2, NR6SO2NR5R6, NR6SO2N(R5)2, NR5SO2NR5R6, NR5SO2N(R5)2, N(OR6)R6, N(OR6)R5, N(OR5)R5, N(OR5)R6, P(O)(OR6)N(R6)2, P(O)(OR6)N(R5R6), P(O)(OR6)N(R5)2, P(O)(OR5)N(R5R6), P(O)(OR5)N(R6)2, P(O)(OR5)N(R5)2, P(O)(OR6)2, P(O)(OR5)2, or P(O)(OR6)(OR5);
• R5 is a C3-C8 cycloaliphatic, C6-C10 aryl, C3-C8 heterocyclic, or C5-C10 heteroaryl ring, optionally substituted with up to 3 R1 substituents;
• R6 is H or C1-C6 aliphatic, wherein R6 is optionally substituted with a R7 substituent;
• R7 is a C3-C8 cycloaliphatic, C6-C10 aryl, C3-C8 heterocyclic, or C5-C10 heteroaryl ring, and each R7is optionally substituted with up to 2 substituents independently chosen from H, C1-C6 aliphatic, or (CH2)m-Z′ wherein m is 0-2;
• Z′ is selected from halo, CN, NO2, C(halo)3, CH(halo)2, CH2(halo), —OC(halo)3, —OCH(halo)2, —OCH2(halo), OH, S—(C1-C6) aliphatic, S(O)—(C1-C6) aliphatic, SO2—(C1-C6)aliphatic, NH2, NH—(C1-C6)aliphatic, N((C1-C6)aliphatic)2, N((C1-C6 )aliphatic)R8, COOH, C(O)O(—(C1-C6)aliphatic), and O—(C1-C6)aliphatic;
• and
• R8 is acetyl, C6-C10 aryl sulfonyl, or C1-C6 alkyl sulfonyl;
• provided that when RM and RN both are hydrogen and Q is a bond, then RQ is not methyl.