Therapeutic agents useful for treating or preventing pain

A compound of formula:

• 24
• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is methyl or halo;
• R3 is:
• (a) —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, or —(CH2)nOR6, which R3 and R4 are each independently unsubstituted or substituted with one or more of —CN, —OH, -halo, —NO2, —CH═NR6, or —NR6OH;
• or
• (b) —H, -halo, —NO2, —CN, or —NH2;
• R4 is:
• —H;
• R5 is:
• (a) —(C1-C6)alkyl, —(C2-C6)alkenyl, or —(C2-C6)alkynyl;
• or
• (b) —(C3-C8)cycloalkyl, —(C5-C5)cycloalkenyl, -phenyl, -napthyl, —(C14)aryl, —(C3-C7)heterocycle, —(C1-C6)alkylphenyl, —(C1-C6)alkylnapthyl, —(C1-C6)alkyl(C14)aryl, —(C1-C6)alkyl(C3-C7)heterocycle, —(C2-C6)alkenylphenyl, —(C2-C6)alkenylnapthyl, —(C2-C6)alkenyl(C14)aryl, —(C2-C6)alkenyl(C3-C7)heterocycle, —(C2-C6)alkynyl(C3-C8)cycloalkyl, —(C2-C6)alkynyl(C5-C8)cycloalkenyl, —(C2-C6)alkynylphenyl, —(C2-C6)alkynylnapthyl, —(C2-C6)alkynyl(C]4)aryl, or —(C2-C6)alkynyl(C3-C7)heterocycle, which is unsubstituted or substituted with one or more R7 groups;
• each R6 is independently —H, —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(C3-C8)cycloalkyl, —(C5-C8)cycloalkenyl, -phenyl, —(C3-C5)heterocycle, C(halo)3, or CH(halo)2;
• each R7 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(CH2)n(C3-C8)cycloalkyl, —(CH2)n(C5-C8)cycloalkenyl, —(CH2)nphenyl, —(CH2)nSR6, —(CH2)nCH(halo)2, —(CH2)nC(halo)3, -halo, —(CH2)nOR6;
• and
• n is an integer ranging from 0 to 2.

A compound of formula:

• 25
• or a pharmaceutically acceptable salt thereof, wherein:
• X is O or S;
• R1 is —CH3 or -halo;
• R3 is:
• (a) —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, or —(CH2)nOR6, which is unsubstituted or substituted with one or more of —CN, —OH, -halo, —NO2, —CH═NR6, or —NR6 OH;
• or
• (b) —H, -halo, —NO2, —CN, or —NH2;
• R4 is —H;
• each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(CH2)n(C3-C8)cycloalkyl, —(CH2)n(C5-C8)cycloalkenyl, —(CH2)nphenyl, —(CH2)nSR6, —(CH2)nCH(halo)2, —(CH2)nC(halo)3, -halo, —(CH2)nOR6;
• each R6 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -phenyl, -napthyl, or —(C14)aryl;
• Ar is -phenyl, -napthyl, —(C14)aryl, —(C3-C8)cycloalkyl or —(C5-C8)cycloalkenyl, which is unsubstituted or substituted with one or more R7 groups;
• each R7 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(CH2)n(C3-C8)cycloalkyl, —(CH2)n(C5-Cg)cycloalkenyl, —(CH2)nphenyl, —(CH2)nSR6, —(CH2)nCH(halo)2, —(CH2)nC(halo)3, -halo, —(CH2)nOR6;
• n is an integer ranging from 0 to 2;
• and
• p is an integer ranging from 0 to 2.

A compound of formula:

• 26
• or a pharmaceutically acceptable salt thereof, wherein:
• X is O or S;
• R1 is —CH3 or -halo;
• R3 is:
• (a) —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, or —(CH2)nOR6, which is unsubstituted or substituted with one or more of —CN, —OH, -halo, —NO2, —CH═NR6, or —NR6OH;
• or
• (b) —H, -halo, —NO2, —CN, or —NH2;
• R4 is —H;
• each R8 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(CH2)n(C3-C8)cycloalkyl, —(CH2)n(C5-C8)cycloalkenyl, —(CH2)nphenyl, —(CH2)nSR6, —(CH2)nCH(halo)2, —(CH2)nC(halo)3, -halo, —(CH2)nOR6;
• each R6 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, -phenyl, -napthyl, or —(C14)aryl;
• Ar is -phenyl, -napthyl, —(C14)aryl, —(C3-C8)cycloalkyl or —(C5-C8)cycloalkenyl, which is unsubstituted or substituted with one or more R7 groups;
• each R7 is independently —(C1-C6)alkyl, —(C2-C6)alkenyl, —(C2-C6)alkynyl, —(CH2)n(C3-C8)cycloalkyl, —(CH2)n(C5-C8)cycloalkenyl, —(CH2)nphenyl, —(CH2)nSR6, —(CH2)nCH(halo)2, —(CH2)nC(halo)3, -halo, —(CH2)nOR1;
• n is an integer ranging from 0 to 2;
• and
• p is an integer ranging from 0 to 2.