Piperidines

A compound having the formula:

• 20
• in which
• R1 is a member selected from
• 21
• R2 is a member selected from substituted or unsubstituted phenyl, and —NR15R16;
• R3 is a member selected from NR15R16, and substituted or unsubstituted phenyl;
• R4 is a member selected from NR15R16;
• R5 is a member selected from hydrogen, nitro, substituted or unsubstituted alkyl, cyano, acyl, and SO2R11
• wherein
• R11 is a member selected from substituted or unsubstituted alkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• Y is a member selected from O and S;
• Z is a member selected from:
• 22
• in which
• A, D, E and M are independently selected from CR12, N, and N-oxide
• wherein
• R12 is a member selected from hydrogen, halo, amino, hydroxy, cyano, nitro, acyl, alkoxy, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroaryl, and
• at least two of A, D, E and M is a selected from CR12, and at most one of A, D, E, and M is N-oxide;
• X is a member selected from O, S, NR10, and C—NO2;
• R6, R7 and R8 are members independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted arylalkyl, and substituted or unsubstituted heterocycloalkyl, and R7 and R8 together with the atom to which they are joined are optionally joined to form a 4- to 8-membered heterocycloalkyl ring.
• R9 is a member selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted and unsubstituted heterocycloalkyl;
• R10 is a member selected from hydrogen, substituted or unsubstituted alkyl, cyano, nitro, acyl, and SO2R11
• the dashed bond marked a is either a single or a double bond;
• and
• n is and integer selected from 0, 1, and 2;
• and
• R15 and R16 are each members independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, and R15 and R16 taken together with the nitrogen atom to which they are attached to form a 4- to 8-membered heterocyclic ring.

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

• 24
• in which
• R1 is a member selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubsituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heteroaryl,
• 25
• R2 is a member selected from substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, alkoxy, —NR15R16
• wherein
• R15 and R16 are each members independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl and R15 and R16 taken together with the nitrogen atom to which they are attached form a 4- to 8-membered heterocyclic ring
• R3 is a member selected from substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and NR15R16;
• R4 is a member selected from substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroaryl, and NR15R16;
• R5 is a member selected from H, nitro, substituted or unsubstituted alkyl, cyano, acyl, and SO2R11
• wherein
• R11 is a member selected from substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• Y is a member selected from O, C—NO2 and S;
• Z is a member selected from:
• 26
• in which
• A, D, E and M are independently selected from CR12, N, and N-oxide,
• wherein
• R12 is a member selected from hydrogen, halo, amino, hydroxy, cyano, nitro, acyl, alkoxy, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroaryl, and at least two of A, D, E and M is a selected from CR12, and at most one of A, D, E, and M is N-oxide;
• X is a member selected from O, C—NO2, S and NR10;
• R6, R7 and R8 are members independently selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aminoalkyl, and R7 and R8 together with the atom to which they are joined are optionally joined to form a 4- to 8-membered heterocycloalkyl ring.
• R9 is a member selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted and unsubstituted heterocycloalkyl, OR20, and SR20;
• wherein
• R20 is a member selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, and substituted and unsubstituted heterocycloalkyl;
• R10 is a member selected from hydrogen cyano, nitro, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocycloalkyl, substituted and unsubstituted heteroaryl and SO2R11;
• the dashed bond marked a is either a single or a double bond;
• and n is and integer selected from 0, 1, and 2.

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

• in which
• R1 is a member selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubsituted arylalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heteroaryl,
• 30
• R2 is a member selected from substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, alkoxy, —NR15R16
• wherein
• R15 and R16 are each members independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl and R15 and R16 taken together with the nitrogen atom to which they are attached form a 4- to 8-membered heterocyclic ring
• R3 is a member selected from substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and NR15R16;
• R4 is a member selected from substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroaryl, and NR15R16;
• R5 is a member selected from H, nitro, substituted or unsubstituted alkyl, cyano, acyl, and SO2R11
• wherein
• R11 is a member selected from substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
• Y is a member selected from O, C—NO2 and S;
• Z is a member selected from:
• 31
• in which
• A, D, E and M are independently selected from CR12, N, and N-oxide, wherein
• R12 is a member selected from hydrogen, halo, amino, hydroxy, cyano, nitro, acyl, alkoxy, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heteroaryl, and at least two of A, D, E and M is a selected from CR12, and at most one of A, D, E, and M is N-oxide;
• X is a member selected from O, C—NO2, S and NR10;
• R6, R7 and R8 are members independently selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted aminoalkyl, and R7 and R8 together with the atom to which they are joined are optionally joined to form a 4- to 8-membered heterocycloalkyl ring.
• R9 is a member selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted and unsubstituted heterocycloalkyl, OR20, and SR20;
• wherein
• R20 is a member selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, and substituted and unsubstituted heterocycloalkyl;
• R10 is a member selected from hydrogen cyano, nitro, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocycloalkyl, substituted and unsubstituted heteroaryl and SO2R11;
• the dashed bond marked a is either a single or a double bond;
• and
• n is and integer selected from 0, 1, and 2.