Ion channel modulators and methods of use

A method of modulating a sodium ion channel comprising the step of contacting said sodium ion channel with a compound of formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• Each X is defined by —ZAR6, wherein each ZA is independently a bond or an optionally substituted branched or straight C1-6 aliphatic chain wherein up to two carbon units of ZA are optionally and independently replaced by —CO—, —CS—, —COCO—, —CONRA—, —CONRANRA—, CO2—, —OCO—, —NRACO2—, —O—, —NRACONRA—, —OCONRA—, —NRANRA, —NRANRACO—, —NRACO—, —S—, —SO—, —SO2—, —NRA—, —SO2NRA—, —NRASO2—, or —NRASO2NRA—;
• Each R6 is independently RA, halo, —OH, —NH2, —NO2, —CN, —CF3, or —OCF3;
• Each RA is independently hydrogen, an optionally substituted C1-8 aliphatic group;
• a 3-8 membered optionally substituted fully saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• an 8-12 membered optionally substituted fully saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or two occurrences of RA are taken together with the atom(s) to which they are attached to form an optionally substituted 3-12 membered fully saturated, partially unsaturated, or fully unsaturated monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• Each n is 1-4;
• Each R1 and R2 is defined by —ZBR7, wherein each ZB is independently a bond or an optionally substituted straight or branched C1-6 aliphatic chain wherein up to two carbon units of ZB are optionally and independently replaced by —CO—, —CS—, —COCO—, —CONRB—, —CONRBNRB—, —CO2—, —OCO—, —NRBCO2—, —O—, —NRBCONRB—, —OCONRB—, —NRBNRB, —NRBNRBCO—, —NRBCO—, —S—, —SO—, —SO2—, —NRB—, —SO2NRB—, —NRBSO2—, or —NRBSO2NRB—;
• Each R7 is independently RB, halo, —OH, —NHC(NH)NH2, —NH2, —NO2, —CN, —CF3, or —OCF3;
• Each RB is independently hydrogen, an optionally substituted C1-8 aliphatic group, an optionally substituted 3-8 membered fully saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• an optionally substituted 8-12 membered fully saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or two occurrences of RB are taken together with the atom(s) to which they are attached to form an optionally substituted 3-12 membered fully saturated, partially unsaturated, or fully unsaturated monocyclic or bicyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• Each R3 and R4 is defined by —ZCR8, wherein each ZC is independently a bond or an optionally substituted straight or branched C1-6 aliphatic chain wherein up to two carbon units of ZC are optionally and independently replaced by —CO—, —CS—, —COCO—, —CONRC—, —CONRCNRC—, —CO2—, —OCO—, —NRCCO2—, —O—, —NRCCONRC—, —OCONRC—, —NRCNRC, —NRCNRCCO—, —NRCCO—, —S—, —SO—, —SO2—, —NRC—, —SO2NRC—, —NRCSO2—, or —NRCSO2NRC—;
• Each R8 is independently RC, halo, —OH, —NH2, —NO2, —CN, —CF3, or —OCF3;
• Each RC is independently hydrogen, or an optionally substituted C1-8 aliphatic group, an optionally substituted 3-8 membered fully saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• an optionally substituted 8-12 membered fully saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• or two occurrences of RC are taken together with the atom(s) to which they are attached to form an optionally substituted 3-12 membered saturated, partially unsaturated, or fully unsaturated monocyclic or bicyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, each of which is optionally substituted with 1 to 3 substituents;
• and
• Each Y is unsubstituted C1-3 alkyl.