Indane derivatives as modulators of 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, or NH, wherein and said ring Z is optionally substituted with z occurrence of RZ;
• z is 0-4;
• RZ is selected from R1, R2, R3, R4, or R5;
• X is a bond, O, NR2, or C(R2)2;
• Q is a bond or a C1-C6 straight or branched alkylidine chain, wherein up to two non-adjacent 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 C1-6 aliphatic group, a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from O, S, N, or 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, or NH;
• wherein RQ is optionally substituted with up to 5 substituents selected from R1, R2, R3, R4, or R5;
• RM and RN are 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, or 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 or 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 R7 is 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), or O—(C1-C6)aliphatic;
• and
• R8 is acetyl, C6-C10 aryl sulfonyl, or C1-C6 alkyl sulfonyl;
• provided that:
• (i) when ring Z is an optionally substituted pyrimidin-2-yl, the sulfonyl group is attached at the 5-position and the N(R2)C(O) group is attached at the 2-position, R2 is H, and X and Q each is a bond, then RQ is not an optionally substituted phenyl or 6-chloro-quinolin-8-yl, fluoren-9-ylethyl, fluoren-9-ylmethyl, indolin-1-yl, cyclohexyl, (phenylthio)methyl, 3-methoxy-thiophen-2-yl, furan-2-yl, (phenoxy)methyl, 3-chloro-thiophen-2-yl, (optionally substituted phenyl)ethyl, or butyl;
• (ii) when ring Z is an optionally substituted pyrimidin-2-yl, the sulfonyl group is attached at the 5-position and the N(R2)C(O) group is attached at the 2-position, R2 is H, and X and Q each is a bond, then RQ is not 2-methyl-5-chloro-2,3-dihydro-benzofuran-7-yl;
• (iii) when ring Z is an optionally substituted pyrimidin-2-yl, the sulfonyl group is attached at the 5-position and the N(R2)C(O) group is attached at the 2-position, R2 is H, and X is —O—, Q is a bond, then RQ is not ethyl or benzyl;
• and
• (iv) when ring Z is an optionally substituted pyrimidin-2-yl, the sulfonyl group is attached at the 5-position and the N(R2)C(O) group is attached at the 2-position, R2 is H, and X is —N(Me)—, Q is a bond, then RQ is not 2-methylphenyl.