# US 11,999,676 B2 · Vesicular monoamine transporter-2 ligands and their use in the treatment of psychostimulant abuse

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- Number: US 11,999,676 B2
- Document ID: US11999676B2
- Status: Granted
- Kind: B2
- Application number: 16/848,462
- Filed: 2020-04-14
- Published: 2020-09-17
- Granted: 2024-06-04
- Earliest claimed: 2016-04-21
- Assignees: University of Kentucky Research Foundation
- Applicants: University of Kentucky Research Foundation
- Inventors: Linda P. Dwoskin; David Watt; Jon Thorson; Mark Leggas; Kip Guy; Jared Hammill; Stefan Kwiatkowski; Derong Ding; Guangrong Zheng; Peter Anthony Crooks; Na-Ra Lee
- Web page: https://patentgrep.com/patent/US11999676B2

## CPC

- C07C 211/53: having the nitrogen atom of at least one of the amino groups further bound to a hydrocarbon radical substituted by amino groups
- C07C 211/49: having at least two amino groups bound to the carbon skeleton
- C07C 233/43: having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
- C07D 209/08: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
- C07D 209/14: Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C07D 213/38: having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
- C07D 215/12: with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 233/61: with hydrocarbon radicals, substituted by nitrogen atoms not forming part of a nitro radical, attached to ring nitrogen atoms
- C07D 239/26: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 333/20: by nitrogen atoms (nitro, nitroso radicals C07D333/12)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention relates to methods of treatment of a disease or pathology of the central nervous system, an eating disorder, or substance use disorder, drug dependence/abuse and withdrawal therefrom comprising administering at least one N-phenylalkyl amphetamine derivative and pharmaceutical compositions comprising at least one N-phenylalkyl amphetamine derivative to an individual in need thereof.

## Claims

### Claim 1

A compound of formula (I):
wherein
m is an integer in the range from 1 to 3;
n is zero or an integer in the range from 1 to 5;
R1 and R2 are independently an aryl group or a heteroaryl group,
wherein R1 is unsubstituted and R2 is substituted with one or more substituents selected from the group consisting of mono-, di-, or tri-tritium; methyl; deuteromethyl (CD3); tritiomethyl (CT3); ethyl; propyl; isopropyl; C4-C7 straight chain or branched alkyl; C3-C6 cycloalkyl; C4-C7 alkenyl (including cis and trans geometrical forms); alkylsulfonyl; alkylsulfinyl; phenylethyl; amino; cycloalkylamine, isopropylamino; N-methylamino; N,N-dimethylamino; carboxylate; methylcarboxylate; ethylcarboxylate; propylcarboxylate; isopropylcarboxylate; carboxaldehyde; acetoxy; propionyloxy; isopropionyloxy; cyano; aminomethyl; N-methylaminomethyl; N,N-dimethylaminomethyl; carboxamide; N-methylcarboxamide; N,N-dimethylcarboxamide; acetyl; propionyl; formyl; benzoyl; sulfate; phenyl; methylsulfate; hydroxyl; methoxy; difluoromethoxy; ethoxy; propoxy; isopropoxy; thiol; methylthio; ethylthio; propiothiol; chloro; bromo; iodo; trifluoromethyl; vinyl; allyl; propargyl; nitro; carbamoyl; ureido; azido; isocyanate; thioisocyanate; hydroxylamino; nitrile; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; an oxygen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; a selenium containing heterocyclic or heteroaryl moiety; a mixed heterocyclic or heteroaryl moiety containing at least two atoms selected from the group consisting of nitrogen, oxygen and sulfur; and ortho-, meta-, or para-substituted benzene;
or wherein R2 is unsubstituted and R1 is substituted with one or more substituents selected from the group consisting of mono-, di-, or tri-tritium; methyl; deuteromethyl (CD3); tritiomethyl (CT3); ethyl; propyl; isopropyl; C4-C7 straight chain or branched alkyl; C3-C6 cycloalkyl; C4-C7 alkenyl (including cis and trans geometrical forms); alkylsulfonyl; alkylsulfinyl; phenylethyl; amino; cycloalkylamine, isopropylamino; N-methylamino; N,N-dimethylamino; carboxylate; methylcarboxylate; ethylcarboxylate; propylcarboxylate; isopropylcarboxylate; carboxaldehyde; acetoxy; propionyloxy; isopropionyloxy; cyano; aminomethyl; N-methylaminomethyl; N,N-dimethylaminomethyl; carboxamide; N-methylcarboxamide; N,N-dimethylcarboxamide; acetyl; propionyl; formyl; benzoyl; sulfate; phenyl; methylsulfate; methoxy; difluoromethoxy; ethoxy; propoxy; isopropoxy; thiol; methylthio; ethylthio; propiothiol; fluoro; chloro; bromo; iodo; vinyl; allyl; propargyl; nitro; carbamoyl; ureido; azido; isocyanate; thioisocyanate; hydroxylamino; nitrile; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; an oxygen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; a selenium containing heterocyclic or heteroaryl moiety; a mixed heterocyclic or heteroaryl moiety containing at least two atoms selected from the group consisting of nitrogen, oxygen and sulfur; and ortho-, meta-, or para-substituted benzene;
or wherein R1 and R2 are substituted with one or more substituents independently selected from the group consisting of mono-, di-, or tri-tritium; methyl; deuteromethyl (CD3); tritiomethyl (CT3); ethyl; propyl; isopropyl; C4-C7 straight chain or branched alkyl; C3-C6 cycloalkyl; C4-C7 alkenyl (including cis and trans geometrical forms); alkylsulfonyl; alkylsulfinyl; phenylethyl; amino; cycloalkylamine, isopropylamino; N-methylamino; N,N-dimethylamino; carboxylate; methylcarboxylate; ethylcarboxylate; propylcarboxylate; isopropylcarboxylate; carboxaldehyde; acetoxy; propionyloxy; isopropionyloxy; cyano; aminomethyl; N-methylaminomethyl; N,N-dimethylaminomethyl; carboxamide; N-methylcarboxamide; N,N-dimethylcarboxamide; acetyl; propionyl; formyl; benzoyl; sulfate; phenyl; methylsulfate; hydroxyl; methoxy; difluoromethoxy; ethoxy; propoxy; isopropoxy; thiol; methylthio; ethylthio; propiothiol; fluoro; chloro; bromo; iodo; trifluoromethyl; vinyl; allyl; propargyl; nitro; carbamoyl; ureido; azido; isocyanate; thioisocyanate; hydroxylamino; nitrile; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; an oxygen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; a selenium containing heterocyclic or heteroaryl moiety; a mixed heterocyclic or heteroaryl moiety containing at least two atoms selected from the group consisting of nitrogen, oxygen and sulfur; and ortho-, meta-, or para-substituted benzene,
wherein one or more of the benzyl; phenyl; saturated or unsaturated hydrocarbon ring; nitrogen containing heterocyclic or heteroaryl moiety; oxygen containing heterocyclic or heteroaryl moiety; sulfur containing heterocyclic or heteroaryl moiety; selenium containing heterocyclic or heteroaryl moiety; mixed heterocyclic or heteroaryl moiety containing at least two atoms selected from the group consisting of nitrogen, oxygen and sulfur; or ortho-, meta-, or para-substituted benzene substituent on R1 or R2 may be independently fused to R1 or R2 or linked to R1 or R2;
R3 is a methyl; ethyl; propyl; isopropyl; hydroxymethyl; 2-hydroxyethyl; 1-hydroxyethyl; methoxymethyl; 2-methoxyethyl; 1-methoxyethyl; aminomethyl; 2-aminoethyl; 1-aminoethyl; N-methylaminomethyl; 2-N-methylaminoethyl; 1-N-methylaminoethyl; N,N-dimethylaminomethyl; 2-N,N-dimethylaminoethyl; 1-N,N-dimethylaminoethyl; methyl, ethyl, propyl, or isopropyl substituted with one or more fluoro; or benzyl;
R4 is an ethyl, propyl, isopropyl, or carbonyl group; or a methyl, ethyl, propyl or isopropyl group substituted with a hydroxyaryl group; and
R5 is hydrogen or methyl; or
an enantiomer; racemate; or pharmaceutically acceptable salt thereof; or
wherein
m is an integer in the range from 1 to 3;
n is zero or an integer in the range from 1 to 5;
R1 and R2 are independently an aryl group or a heteroaryl group,
wherein R2 is unsubstituted and R1 is substituted with one or more substituents selected from the group consisting of mono-, di-, or tri-tritium; methyl; deuteromethyl (CD3); tritiomethyl (CT3); ethyl; propyl; isopropyl; C4-C7 straight chain or branched alkyl; C3-C6 cycloalkyl; C4-C7 alkenyl (including cis and triflcycloalkylamine, isopropylamino; N-methylamino; N,N-dimethylamino; carboxylate; methylcarboxylate; ethylcarboxylate; propylcarboxylate; isopropylcarboxylate; carboxaldehyde; acetoxy; propionyloxy; isopropionyloxy; cyano; aminomethyl; N-methylaminomethyl; N,N-dimethylaminomethyl; carboxamide; N-methylcarboxamide; N,N-dimethylcarboxamide; acetyl; propionyl; formyl; benzoyl; sulfate; phenyl; methylsulfate; difluoromethoxy; ethoxy; propoxy; isopropoxy; thiol; methylthio; ethylthio; propiothiol; chloro; iodo; vinyl; allyl; propargyl; carbamoyl; ureido; azido; isocyanate; thioisocyanate; hydroxylamino; nitrile; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; an oxygen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; a selenium containing heterocyclic or heteroaryl moiety; a mixed heterocyclic or heteroaryl moiety containing at least two atoms selected from the group consisting of nitrogen, oxygen and sulfur; and ortho-, meta-, or para-substituted benzene;
or wherein R1 and R2 are substituted with one or more substituents independently selected from the group consisting of mono-, di-, or tri-tritium; methyl; deuteromethyl (CD3); tritiomethyl (CT3); ethyl; propyl; isopropyl; C4-C7 straight chain or branched alkyl; C3-C6 cycloalkyl; C4-C7 alkenyl (including cis and trans geometrical forms); alkylsulfonyl; alkylsulfinyl; phenylethyl; cycloalkylamine, isopropylamino; N-methylamino; N,N-dimethylamino; carboxylate; methylcarboxylate; ethylcarboxylate; propylcarboxylate; isopropylcarboxylate; carboxaldehyde; acetoxy; propionyloxy; isopropionyloxy; cyano; aminomethyl; N-methylaminomethyl; N,N-dimethylaminomethyl; carboxamide; N-methylcarboxamide; N,N-dimethylcarboxamide; acetyl; propionyl; formyl; benzoyl; sulfate; phenyl; methylsulfate; difluoromethoxy; ethoxy; propoxy; isopropoxy; thiol; methylthio; ethylthio; propiothiol; chloro; iodo; trifluoromethyl; vinyl; allyl; propargyl; carbamoyl; ureido; azido; isocyanate; thioisocyanate; hydroxylamino; nitrile; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; an oxygen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; a selenium containing heterocyclic or heteroaryl moiety; a mixed heterocyclic or heteroaryl moiety containing at least two atoms selected from the group consisting of nitrogen, oxygen and sulfur; and ortho-, meta-, or para-substituted benzene,
wherein one or more of the benzyl; phenyl; saturated or unsaturated hydrocarbon ring; nitrogen containing heterocyclic or heteroaryl moiety; oxygen containing heterocyclic or heteroaryl moiety; sulfur containing heterocyclic or heteroaryl moiety; selenium containing heterocyclic or heteroaryl moiety; mixed heterocyclic or heteroaryl moiety containing at least two atoms selected from the group consisting of nitrogen, oxygen and sulfur; or ortho-, meta-, or para-substituted benzene substituent on R1 or R2 may be independently fused to R1 or R2 or linked to R1 or R2;
R3 is a methyl; ethyl; propyl; isopropyl; hydroxymethyl; 2-hydroxyethyl; 1-hydroxyethyl; methoxymethyl; 2-methoxyethyl; 1-methoxyethyl; aminomethyl; 2-aminoethyl; 1-aminoethyl; N-methylaminomethyl; 2-N-methylaminoethyl; 1-N-methylaminoethyl; N,N-dimethylaminomethyl; 2-N,N-dimethylaminoethyl; 1-N,N-dimethylaminoethyl; methyl, ethyl, propyl, or isopropyl substituted with one or more fluoro; or benzyl;
R4 is a hydrogen atom or a methyl; and
R5 is a hydrogen or a methyl; or
an enantiomer; racemate; or pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound of claim 1, wherein
m is 1;
n is 2;
R3 is methyl; and
R5 is a hydrogen atom or a methyl; or
an enantiomer; racemate; or pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 2)

The compound of claim 2, wherein:
R5 is hydrogen; or
an enantiomer; racemate; or pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

The compound of claim 1, wherein
m is 1;
n is 2;
R1 and R2 are independently an aryl group or a heteroaryl group,
wherein R1 is unsubstituted and is R2 substituted with one or more substituents selected from the group consisting of methyl; alkylsulfonyl; alkylsulfinyl; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; phenyl; amino; cycloalkylamine; isopropylamino; N-methylamino; N,N-dimethylamino; ethylcarboxylate; carboxamide; N-methylcarboxamide; hydroxyl; methoxy; difluoromethoxy; thiol; fluoro; chloro; bromo; iodo; trifluoromethyl; nitro; and nitrile;
or wherein R2 is unsubstituted and R1 is substituted with one or more substituents selected from the group consisting of methyl; alkylsulfonyl; alkylsulfinyl; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; phenyl; amino; cycloalkylamine; isopropylamino; N-methylamino; N,N-dimethylamino; ethylcarboxylate; carboxamide; N-methylcarboxamide; methoxy; difluoromethoxy; thiol; fluoro; chloro; bromo; iodo; nitro; and nitrile;
or wherein R1 and R2 are substituted with one or more substituents independently selected from the group consisting of methyl; alkylsulfonyl; alkylsulfinyl; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; phenyl; amino; cycloalkylamine; isopropylamino; N-methylamino; N,N-dimethylamino; ethylcarboxylate; carboxamide; N-methylcarboxamide; hydroxyl; methoxy; difluoromethoxy; thiol; fluoro; chloro; bromo; iodo; trifluoromethyl; nitro; and nitrile,
wherein one or more of the phenyl; saturated or unsaturated hydrocarbon ring; nitrogen containing heterocyclic or heteroaryl moiety; sulfur containing heterocyclic or heteroaryl moiety substituent on R1 or R2 may be independently fused to R1 or R2 or linked to R1 or R2;
R3 is a methyl, ethyl, isopropyl, hydroxymethyl, or methyl substituted with one or more fluoro; or benzyl; and
R4 is a carbonyl group; or an ethyl, propyl or isopropyl group substituted with a hydroxyaryl group; and
R5 is a hydrogen or a methyl; or
an enantiomer; racemate; or pharmaceutically acceptable salt thereof; or
wherein
m is 1;
n is 2;
R1 and R2 are independently an aryl group or a heteroaryl group,
wherein R1 is unsubstituted and R2 is substituted with one or more substituents selected from the group consisting of methyl; alkylsulfonyl; alkylsulfinyl; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; phenyl; amino; cycloalkylamine; isopropylamino; N-methylamino; N,N-dimethylamino; ethylcarboxylate; carboxamide; N-methylcarboxamide; hydroxyl; methoxy; difluoromethoxy; thiol; chloro; bromo; iodo; trifluoromethyl; nitro; and nitrile;
or wherein R2 is unsubstituted and R1 is substituted with one or more substituents selected from the group consisting of methyl; alkylsulfonyl; alkylsulfinyl; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; phenyl; cycloalkylamine; isopropylamino; N-methylamino; N,N-dimethylamino; ethylcarboxylate; carboxamide; N-methylcarboxamide; difluoromethoxy; thiol; chloro; iodo; and nitrile;
or wherein R1 and R2 are substituted with one or more substituents independently selected from the group consisting of methyl; alkylsulfonyl; alkylsulfinyl; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; phenyl; cycloalkylamine; isopropylamino; N-methylamino; N,N-dimethylamino; ethylcarboxylate; carboxamide; N-methylcarboxamide; difluoromethoxy; thiol; chloro; iodo; trifluoromethyl; and nitrile,
wherein one or more of the phenyl; saturated or unsaturated hydrocarbon ring; nitrogen containing heterocyclic or heteroaryl moiety; sulfur containing heterocyclic or heteroaryl moiety substituent on R1 or R2 may be independently fused to R1 or R2 or linked to R1 or R2;
R3 is a methyl, ethyl, isopropyl, hydroxymethyl, or methyl substituted with one or more fluoro; or benzyl; and
R4 is a hydrogen atom or a methyl; and
R5 is a hydrogen or a methyl; or
an enantiomer; racemate; or pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 2)

The compound of claim 2, wherein
R1 is a pyridyl group; a pyrimidyl group; an unsubstituted phenyl; or a phenyl substituted with chloro, difluoro, carboxamide, or pyridinyl, and
R2 is a indolyl group; a pyridyl group; a pyrazolyl group; an imidazolyl group; a quinolinyl group; a methylpyrazolyl group; an unsubstituted phenyl; or a phenyl substituted with chloro, bromo, iodo, trifluoromethyl, methoxy, carboxamide, methylcarboxamide, amine, aminoisopropyl, aminocyclobutyl, dimethylamino, nitro, methylsulfonyl, methylsulfinyl, ethylcarboxylate, pyrimidinyl, pyridinyl, indolyl, thiophene, or hydroxyl; or
an enantiomer; racemate; or pharmaceutically acceptable salt thereof.

### Claim 6

A compound selected from the group consisting of
or
an enantiomer; racemate; or pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 1)

A pharmaceutical composition comprising a compound of formula (I) as in claim 1, or an enantiomer; racemate; or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive.

### Claim 8 (depends on 7)

The pharmaceutical composition of claim 7, wherein
m is 1;
n is 2;
R3 is methyl; and
R5 is a hydrogen atom or a methyl; or
an enantiomer; racemate; or pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 8)

The pharmaceutical composition of claim 8, wherein:
R5 is hydrogen; or
an enantiomer; racemate; or pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 7)

The pharmaceutical composition of claim 7, wherein
m is 1;
n is 2;
R1 and R2 are independently an aryl group or a heteroaryl group,
wherein R1 is unsubstituted and R2 is substituted with one or more substituents selected from the group consisting of methyl; alkylsulfonyl; alkylsulfinyl; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; phenyl; amino; cycloalkylamine; isopropylamino; N-methyl amino; N,N-dimethylamino; ethylcarboxylate; carboxamide; N-methylcarboxamide; hydroxyl; methoxy; difluoromethoxy; thiol; chloro; bromo; iodo; trifluoromethyl; nitro; and nitrile;
or wherein R2 is unsubstituted and R1 is substituted with one or more substituents selected from the group consisting of methyl; alkylsulfonyl; alkylsulfinyl; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; phenyl; amino; cycloalkylamine; isopropylamino; N-methyl amino; N,N-dimethylamino; ethylcarboxylate; carboxamide; N-methylcarboxamide; methoxy; difluoromethoxy; thiol; fluoro; chloro; bromo; iodo; nitro; and nitrile;
or wherein R1 and R2 are substituted with one or more substituents independently selected from the group consisting of methyl; alkylsulfonyl; alkylsulfinyl; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; phenyl; amino; cycloalkylamine; isopropylamino; N-methyl amino; N,N-dimethylamino; ethylcarboxylate; carboxamide; N-methylcarboxamide; hydroxyl; methoxy; difluoromethoxy; thiol; fluoro; chloro; bromo; iodo; trifluoromethyl; nitro; and nitrile,
wherein one or more of the phenyl; saturated or unsaturated hydrocarbon ring; nitrogen containing heterocyclic or heteroaryl moiety; sulfur containing heterocyclic moiety or heteroaryl substituent on R1 or R2 may be independently fused to R1 or R2 or linked to R1 or R2;
R3 is a methyl, ethyl, isopropyl, hydroxymethyl, or methyl substituted with one or more fluoro; or benzyl; and
R4 is a carbonyl group; or an ethyl, propyl or isopropyl group substituted with a hydroxyaryl group; and
R5 is hydrogen or methyl; or
an enantiomer; racemate; or pharmaceutically acceptable salt thereof; or
wherein
m is 1;
n is 2;
R1 and R2 are independently an aryl group or a heteroaryl group,
wherein R1 is unsubstituted and R2 is substituted with one or more substituents selected from the group consisting of methyl; alkylsulfonyl; alkylsulfinyl; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; phenyl; amino; cycloalkylamine; isopropylamino; N-methyl amino; N,N-dimethylamino; ethylcarboxylate; carboxamide; N-methylcarboxamide; hydroxyl; methoxy; difluoromethoxy; thiol; chloro; bromo; iodo; trifluoromethyl; nitro; and nitrile;
or wherein R2 is unsubstituted and R1 is substituted with one or more substituents selected from the group consisting of methyl; alkylsulfonyl; alkylsulfinyl; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; phenyl; cycloalkylamine; isopropylamino; N-methyl amino; N,N-dimethylamino; ethylcarboxylate; carboxamide; N-methylcarboxamide; difluoromethoxy; thiol; chloro; iodo; and nitrile;
or wherein R1 and R2 are substituted with one or more substituents independently selected from the group consisting of methyl; alkylsulfonyl; alkylsulfinyl; a saturated or unsaturated hydrocarbon ring; a nitrogen containing heterocyclic or heteroaryl moiety; a sulfur containing heterocyclic or heteroaryl moiety; phenyl; cycloalkylamine; isopropylamino; N-methyl amino; N,N-dimethylamino; ethylcarboxylate; carboxamide; N-methylcarboxamide; difluoromethoxy; thiol; chloro; iodo; trifluoromethyl; and nitrile,
wherein one or more of the phenyl; saturated or unsaturated hydrocarbon ring; nitrogen containing heterocyclic or heteroaryl moiety; sulfur containing heterocyclic moiety or heteroaryl substituent on R1 or R2 may be independently fused to R1 or R2 or linked to R1 or R2;
R3 is a methyl, ethyl, isopropyl, hydroxymethyl, or methyl substituted with one or more fluoro; or benzyl; and
R4 is a hydrogen atom or a methyl; and
R5 is a hydrogen or a methyl; or
an enantiomer; racemate; or pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 7)

The pharmaceutical composition of claim 7, wherein
R1 is a pyridyl group; a pyrimidyl group; an unsubstituted phenyl; or a phenyl substituted with chloro, difluoro, carboxamide, amino, or pyridinyl; and
R2 is a indolyl group; a pyridyl group; a pyrazolyl group; an imidazolyl group; a quinolinyl group; a methylpyrazolyl group; an unsubstituted phenyl; or a phenyl substituted with chloro, bromo, iodo, trifluoromethyl, methoxy, carboxamide, methylcarboxamide, amine, aminoisopropyl, aminocyclobutyl, dimethylamino, nitro, methyl sulfonyl, methylsulfinyl, ethylcarboxylate, pyrimidinyl, pyridinyl, indolyl, thiophene, or hydroxyl; or
an enantiomer; racemate; or pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 6)

A pharmaceutical composition comprising any one of the compounds of claim 6, or an enantiomer; racemate; or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive.