AMINE PRODRUGS OF PHARMACEUTICAL COMPOUNDS

1 . A prodrug comprising a drug molecule and at least one or more prodrug appendage moieties, the prodrug is formed as:

wherein the prodrug appendage moiety is coupled to amine of the drug molecule, and i is 1 or 2 and j is 0 or 1.

2 . The prodrug of claim 1 , wherein prodrug appendage moiety is independently selected from the group of consisting of:

where R 1 is H, alkyl or particularly C 1 -C 8 alkyl;

R 2 is alkyl, cycloalkyl, aryl, or heteroaryl, or halo alkyl, which is substituted or unsubstituted.

R 3 is H, metal, R 2 or a substituted or unsubstituted primary, secondary or tertiary amine;

R 4 is H, metal, ammonium salt or alkyl;

R 5 is a substituted or unsubstituted natural amino acid;

R a or R b is H, alkyl or aryl; or NR a or NR b is an amino acid;

X is C or O;

k is 1 or 2, m is 2-22, or (CH k ) m is saturated, unsaturated or conjugated hydrocarbon;

n is0-2;

the metal is Na, K, Li, Ca, Mg, Ag or Zn.

3 . The prodrug of claim 1 wherein i is 1 and j is 1,

4 . The prodrug of claim 1 , wherein i is 2 and j is 0.

5 . The prodrug of claim 1 , wherein the drug molecule riluzole.

6 . A method of preparing a riluzole prodrug, comprising a step of coupling one or more prodrug appendage moieties to a riluzole molecule

wherein the prodrug appendage moiety is coupled to amine of the riluzole molecule, and i is 1 or 2 and j is 0 or 1.

7 . The method of claim 6 , wherein each prodrug appendage moiety is independently selected from the group of consisting of:

where R 1 is H, alkyl or particularly C 1 -C 8 alkyl;

R 2 is alkyl, cycloalkyl, aryl, or heteroaryl, or halo alkyl, which is substituted or unsubstituted,

R 3 is H, metal, R 2 or a substituted or unsubstituted primary, secondary or tertiary amine;

R 4 is H, metal, ammonium salt or alkyl;

R 5 is a substituted or unsubstituted natural amino acid;

R a or R b is H, alkyl or aryl; or NR a or NR b is an amino acid;

X is C or O;

k is 1 or 2, m is 2-22, or (CH k ) m is saturated, unsaturated or conjugated hydrocarbon;

n is 0-2;

is 2-12; and

the metal is Na, K, Li, Mg, Ca, Ag or Zn.

8 . The method of claim 6 , wherein i is 1 and is 1.

9 . The method of claim 6 , wherein i is 2 and j is 0.

10 . The method of claim 6 , wherein the riluzole prodrug is selected from the group consisting of:

where R 1 is H, alkyl, or particularly C 1 -C 8 alkyl;

R 2 is alkyl, cycloalkyl, aryl, or heteroaryl, or halo alkyl, which is substituted or unsubstituted;

R 3 is H, metal, R 2 or a substituted or unsubstituted primary, secondary or tertiary amine;

R 4 is H, metal, ammonium salt or alkyl;

R 5 is a substituted or unsubstituted natural amino acid;

R 6 is alkyl, cycloalkyl, aryl, or heteroaryl, or halo alkyl;

k is 1 or 2, m is 2-22, or (CH k ) m is saturated, unsaturated or conjugated hydrocarbon;

N′ is a primary, secondary and tertiary amine which is substituted or unsubstituted, or metal salts;

Y is PO 3 H, CH 2 PO 3 H or salt thereof; and

the metal is Na, K, Li, Ca, Mg, Ag or Zn.

11 . A method of synthesizing a riluzole prodrug, comprising a step of reacting riluzole with

to produce

12 . The method of claim 11 , further comprising a step of reacting

with a compound selected from the group consisting of:

wherein R 2 is H, alkyl or particularly C 1 -C 8 alkyl

R 2 is alkyl, cycloalkyl, aryl, or heteroaryl, or halo alkyl, which is substituted or unsubstituted;

R 4 is H, metal, ammonium salt, or alkyl,

k is 1 or 2, m is 2-22, or (CH k ) m is saturated, unsaturated pr conjugated hydrocarbon;

Bc is a protecting group;

Y′ is H, PO 3 Bc 2 , CH 2 PO 2 Bc, or salt thereof, or N(R a ) 4 + , where Ra is H or alkyl;

M is Na, K, Li, Mg, Ca, Ag or Zn; and

R′ or R″ are cyclic or acyclic alkyl.

13 . A method of synthesizing a riluzole prodrug, comprising a step of reacting a riluzole, with CO 2 , Cs 2 CO 3 and reacting the resulting compound with

wherein Lg is a leaving group.

14 . A method of synthesizing a riluzole prodrug, comprising a step of reacting a riluzole with

wherein Lg is a leaving group and where R 1 is H, or C 1 -C 8 alkyl.

15 . A method of synthesizing a riluzole prodrug, comprising a step of reacting a riluzole with

wherein Lg is a leaving group.

16 . A method of synthesizing a riluzole prodrug, comprising a step of reacting riluzole with

wherein R I is H, alkyl or particularly C 1 -C 8 alkyl: and

R 2 is alkyl, cycloalkyl, aryl, or heteroaryl, or halo alkyl, which is substituted or unsubstituted.

17 . A method of synthesizing a riluzole prodrug, col prising a step of reacting riluzole with ((PhCH 2 O) 2 PO) 2 O and sodium his(trimethylsily)amide (NaHMDS) and subsequently reacting the resulting compound with hydrogen:

wherein R 6 is alkyl, cycloalkyl, aryl,or heteroaryl, or haloalkyl; N′ is a primary, secondary and tertiary amine N, which is substituted or unsubstituted, or metal salts.