Pyridine-substituted benzanilides as potassium ion channel openers

A method of increasing ion flow through voltage-dependent potassium channels in a cell, said method comprising contacting said cell with a potassium channel-opening amount of a compound of the formula:

• wherein
• Y is a member selected from H, methyl, methoxy, trifluoromethoxy, —CF3 or halo;
• V and X are members independently selected from H, halo, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower heteroalkyl, NO2, CN, CF3, C(O)NR11R12 and C(O)R13;
• R1, R11, R12 and R13 are members independently selected from substituted or unsubstituted lower alkyl, substituted or unsubstituted lower heteroalkyl, substituted or unsubstituted carbocycle, substituted or unsubstituted heterocycle, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, in which R11 and R12 optionally can be joined into a ring;
• Q and W are members independently selected from —(CR2R3)t—(CH2)n—, —(CH2)n—(CR2R3)t,—C(R4)═C(R5)—, and —C≡C— wherein
• R2 and R3 are members independently selected from H, F, substituted or unsubstituted lower alkyl or substituted or unsubstituted lower heteroalkyl, in which R2 and R3 are optionally joined to form a cyclic structure which is a member selected from the group consisting of cycloalkyl and heterocycle groups, or R2 and R3 together with the carbon to which they are attached form —C(O)—;
• Z represents —O—, —S(O)m—, —N(R4)—, —N(R4)C(O)—, —C(O)N(R4)—, —C(O)—, —N(R4)C(O)N(R5)—, —N(R4)C(O)O—, (CR2R3)t, and —SO2N(R4)—, wherein
• R4 and R5 are members independently selected from the group consisting of H, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower heteroalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, in which R1 is optionally joined together with either X or R4 to form a substituted or unsubstituted heterocycle;
• m is an integer from 0 to 2, inclusive;
• n is an integer from 0 to 3, inclusive;
• and
• t is an integer from 0 to 2, inclusive.

A method of treating a central or peripheral nervous system disorder or condition through modulation of a voltage-dependent potassium channel, said method comprising administering to a subject in need of such treatment, an effective amount of a compound having the formula:

• wherein
• Y is a member selected from H, methyl, methoxy, trifluoromethoxy, —CF3 or halo;
• V and X are members independently selected from H, halo, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower heteroalkyl, NO2, CN, CF3, C(O)NR11R12 and C(O)R13;
• R1,R11,R12 and R13 are members independently selected from substituted or unsubstituted lower alkyl, substituted or unsubstituted lower heteroalkyl, substituted or unsubstituted carbocycle, substituted or unsubstituted heterocycle, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, in which R11 and R12 optionally can be joined into a ring;
• Q and W are members independently selected from —(CR2R3)t—(CH2)n—, —(CH2)n—(CR2R3)t, —C(R4)═C(R5)—, and —C≡C— wherein
• R2 and R3 are members independently selected from H, F, substituted or unsubstituted lower alkyl or substituted or unsubstituted lower heteroalkyl, in which R2 and R3 are optionally joined to form a cyclic structure which is a member selected from the group consisting of cycloalkyl and heterocycle groups, or R2 and R3 together with the carbon to which they are attached form —C(O)—;
• Z represents —O—, —S(O)m—, —N(R4)—, —N(R4)C(O)—, —C(O)N(R4)—, —C(O)—, —N(R4)C(O)N(R5)—, —N(R4)C(O)O—, (CR2R3)t, and —SO2N(R4)—, wherein
• R4 and R5 are members independently selected from the group consisting of H, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower heteroalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, in which R1 is optionally joined together with either X or R4 to form a substituted or unsubstituted heterocycle;
• m is an integer from 0 to 2, inclusive;
• n is an integer from 0 to 3, inclusive;
• and
• t is an integer from 0 to 2, inclusive.

A method of treating a member selected from the group consisting of pain, anxiety and bipolar disorder through modulation of a voltage-dependent potassium channel, said method comprising administering to a subject in need of such treatment, an effective amount of a compound having the formula:

• wherein
• Y is a member selected from H, methyl, methoxy, trifluoromethoxy, —CF3 or halo;
• V and X are members independently selected from H, halo, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower heteroalkyl, NO2, CN, CF3, C(O)NR11R12 and C(O)R13;
• R1, R11, R12 and R13 are members independently selected from substituted or unsubstituted lower alkyl, substituted or unsubstituted lower heteroalkyl, substituted or unsubstituted carbocycle, substituted or unsubstituted heterocycle, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, in which R11 and R12 optionally can be joined into a ring;
• Q and W are members independently selected from —(CR2R3)t—(CH2)n—, —(CH2)n—(CR2R3)t, —C(R4)═C(R5)—, and —C≡C— wherein
• R2 and R3 are members independently selected from H, F, substituted or unsubstituted lower alkyl or substituted or unsubstituted lower heteroalkyl, in which R2 and R3 are optionally joined to form a cyclic structure which is a member selected from the group consisting of cycloalkyl and heterocycle groups, or R2 and R3 together with the carbon to which they are attached form —C(O)—;
• Z represents —O—, —S(O)m—, —N(R4)—, —N(R4)C(O)—, —C(O)N(4)—, —C(O)—, —N(R4)C(O)N(R5)—, —N(4)C(O)O—, (CR2R3)t, and —SO2N(R4)—, wherein
• R4 and R5 are members independently selected from the group consisting of H, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower heteroalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, in which R1 is optionally joined together with either X or R4 to form a substituted or unsubstituted heterocycle;
• m is an integer from 0 to 2, inclusive;
• n is an integer from 0 to 3, inclusive;
• and
• t is an integer from 0 to 2, inclusive.

A composition comprising a pharmaceutically acceptable excipient and a compound of the formula:

• wherein
• Y is a member selected from H, methyl, methoxy, trifluoromethoxy, —CF3 or halo;
• V and X are members independently selected from H, halo, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower heteroalkyl, NO2, CN, CF3, C(O)NR11R12 and C(O)R13;
• R1, R11, R12 and R13 are members independently selected from substituted or unsubstituted lower alkyl, substituted or unsubstituted lower heteroalkyl, substituted or unsubstituted carbocycle, substituted or unsubstituted heterocycle, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, in which R11 and R12 optionally can be joined into a ring;
• Q and W are members independently selected from —(CR2R3)t—(CH2)n—, —(CH2)n—(CR2R3)t, —C(R4)═C(R5)—, and —C≡C— wherein
• R2 and R3 are members independently selected from H, F, substituted or unsubstituted lower alkyl or substituted or unsubstituted lower heteroalkyl, in which R2 and R3 are optionally joined to form a cyclic structure which is a member selected from the group consisting of cycloalkyl and heterocycle groups, or R2 and R3 together with the carbon to which they are attached form —C(O)—;
• Z represents —O—, —S(O)m—, —N(R4)—, —N(R4)C(O)—, —C(O)N(R4)—, —C(O)—, —N(R4)C(O)N(R5)—, —N(R4)C(O)O—, (CR2R3)t, and —SO2N(R4)—, wherein
• R4 and R5 are members independently selected from the group consisting of H, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower heteroalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, in which R1 is optionally joined together with either X or R4 to form a substituted or unsubstituted heterocycle;
• m is an integer from 0 to 2, inclusive;
• n is an integer from 0 to 3, inclusive;
• and
• t is an integer from 0 to 2, inclusive.