Heterocyclic thioester and ketone hair growth compositions and uses

A method for treating alopecia or promoting hair growth in an animal in need thereof, which comprises administering to said animal an effective amount of a compound of formula I

• or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein:
• A and B, taken together with the nitrogen and carbon atoms to which they are respectively attached, form a 5-7 membered saturated or unsaturated heterocyclic ring which has one or more O, S, SO, SO2, N, NH, or NR2 heteroatom(s);
• X is either O or S;
• Z is either S, CH2, CHR1 or CR1R3;
• W and Y are independently O, S, CH2 or H2;
• R1 and R3 are independently C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl, wherein said alkyl or alkenyl is substituted with one or more substituent(s) independently selected from the group consisting of (Ar1)n, C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl substituted with (Ar1)n, C3-C8 cycloalkyl, C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl substituted with C3-C8 cycloalkyl, and Ar2;
• n is 1 or 2;
• R2 is either C1-C9 straight or branched chain alkyl, C2-C9 straight or branched chain alkenyl, C3-C8 cycloalkyl, C5-C7 cycloalkenyl or Ar1, wherein said alkyl, alkenyl, cycloalkyl or cycloalkenyl is either unsubstituted or substituted with one or more substituent(s) independently selected from the group consisting of C1-C4 straight or branched chain alkyl, C2-C4 straight or branched chain alkenyl, and hydroxy;
• and
• Ar1 and Ar2 are independently an alicyclic or aromatic, mono-, bi- or tricyclic, carbo- or heterocyclic ring, wherein said ring is either unsubstituted or substituted with one or more substituent(s) independently selected from the group consisting of halo, hydroxy, nitro, trifluoromethyl, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, C1-C4 alkoxy, C2-C6 alkenyloxy, phenoxy, benzyloxy, and amino;
• wherein the individual ring size is 5-8 members;
• and wherein the heterocyclic ring has 1-6 heteroatom(s) independently selected from the group consisting of O, N, and S.

A method for treating alopecia or promoting hair growth in an animal in need thereof, which comprises administering to said animal an effective amount of a compound of formula II

• or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein:
• n is 1 or 2;
• X is O or S;
• Z is selected from the group consisting of S, CH2, CHR1, and CR1R3;
• R1 and R3 are independently selected from the group consisting of C1-C5 straight or branched chain alkyl, C2-C5 straight or branched chain alkenyl, and Ar1, wherein said R1 is unsubstituted or substituted with one or more substituent(s) independently selected from the group consisting of halo, nitro, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, hydroxy, C1-C4 alkoxy, C2-C4 alkenyloxy, phenoxy, benzyloxy, amino, and Ar1;
• R2 is selected from the group consisting of C1-C9 straight or branched chain alkyl, C2-C9 straight or branched chain alkenyl, C3-C8 cycloalkyl, C5-C7 cycloalkenyl, and Ar1;
• and
• Ar1 is phenyl, benzyl, pyridyl, fluorenyl, thioindolyl or naphthyl, wherein said Ar1 is unsubstituted or substituted with one or more substituent(s) independently selected from the group consisting of halo, trifluoromethyl, hydroxy, nitro, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, C1-C4 alkoxy, C2-C4 alkenyloxy, phenoxy, benzyloxy, and amino.

A method for treating alopecia or promoting hair growth in an animal in need thereof, which comprises administering to said animal an effective amount of a compound of formula III

• or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein:
• A, B, and C are independently CH2, O, S, SO, SO2, NH or NR2;
• X is O or S;
• Z is S, CH2, CHR1, or CR1R3;
• R1 and R3 are independently C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl, wherein said alkyl or alkenyl is substituted with one or more substituent(s) independently selected from the group consisting of (Ar1)n, C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl substituted with (Ar1)n, C3-C8 cycloalkyl, C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl substituted with C3-C8 cycloalkyl, and Ar2;
• R2 is either C1-C9 straight or branched chain alkyl or C2-C9 straight or branched chain alkenyl, C3-C8 cycloalkyl, C5-C7 cycloalkenyl or Ar1, wherein said alkyl, alkenyl, cycloalkyl or cycloalkenyl is either unsubstituted or substituted with one or more substituent(s) independently selected from the group consisting of C1-C4 straight or branched chain alkyl, C2-C4 straight or branched chain alkenyl, and hydroxy;
• and
• Ar1 and Ar2 are independently an alicyclic or aromatic, mono-, bi- or tricyclic, carbo- or heterocyclic ring, wherein said ring is either unsubstituted or substituted with one or more substituent(s) independently selected from the group consisting of halo, hydroxy, nitro, trifluoromethyl, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, C1-C4 alkoxy, C2-C4 alkenyloxy, phenoxy, benzyloxy, and amino;
• wherein the individual ring size is 5-8 members;
• and wherein the heterocyclic ring has 1-6 heteroatom(s) independently selected from the group consisting of O, N, and S.

A method for treating alolecia or promoting hair growth in an animal in need thereof, which comprises administering to said animal an effective amount of a compound of formula IV

• or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein
• A, B, C and D are independently CH2, O, S, SO, SO2, NH, or NR2;
• X is O or S;
• Z is S, CH2, CHR1, or CR1R3;
• R1 and R3 are independently C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl, wherein said alkyl or alkenyl is substituted with one or more substituent(s) independently selected from the group consisting of (Ar1)n, C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl substituted with (Ar1)n, C3-C8 cycloalkyl, C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl substituted with C3-C8 cycloalkyl, and Ar2;
• n is 1 or 2;
• R2 is either C1-C9 straight or branched chain alkyl or C2-C9 straight or branched chain alkenyl, C3-C8 cycloalkyl, C5-C7 cycloalkenyl or Ar1, wherein said alkyl, alkenyl, cycloalkyl or cycloalkenyl is either unsubstituted or substituted with one or more substituent(s) independently selected from the group consisting of C1-C4 straight or branched chain alkyl, C2-C4 straight or branched chain alkenyl, and hydroxy;
• and
• Ar1 and Ar2 are independently an alicyclic or aromatic, mono-, bi- or tricyclic, carbo- or heterocyclic ring, wherein said ring is either unsubstituted or substituted with one or more substituent(s) independently selected from the group consisting of halo, hydroxy, nitro, trifluoromethyl, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, C1-C4 alkoxy, C2-C4 alkenyloxy, phenoxy, benzyloxy, and amino;
• wherein the individual ring size is 5-8 members;
• and wherein the heterocyclic ring has 1-6 heteroatom(s) independently selected from the group consisting of O, N, and S.

A method for treating alopecia or promoting hair growth in an animal in need thereof, which comprises administering to said animal an effective amount of a compound of formula V

• or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein:
• V is C, N, or S;
• A and B, taken together with V and the carbon atom to which they are respectively attached, form a 5-7 membered saturated or unsaturated heterocyclic ring which has one or more heteroatom(s) independently selected from the group consisting of O, S, SO, SO2, N, NH, and NR4;
• R4 is either C1-C9 straight or branched chain alkyl, C2-C9 straight or branched chain alkenyl, C3-C9 cycloalkyl, C5-C7 cycloalkenyl, or Ar3, wherein R4 is either unsubstituted or substituted with one or more substituent(s) independently selected from the group consisting of halo, haloalkyl, carbonyl, carboxy, hydroxy, nitro, trifluoromethyl, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, C1-C4 alkoxy, C2-C4 alkenyloxy, phenoxy, benzyloxy, thioalkyl, alkylthio, sulfhydryl, amino, alkylamino, aminoalkyl, aminocarboxyl, and Ar4;
• and
• Ar3 and Ar4 are independently an alicyclic or aromatic, mono-, bi- or tricyclic, carbo- or heterocyclic ring;
• wherein the individual ring size is 5-8 members;
• wherein said heterocyclic ring has 1-6 heteroatom(s) independently selected from the group consisting of O, N, and S;
• X is either O or S;
• Z is either S, CH2, CHR1 or CR1R3;
• W and Y are independently O, S, CH2 or H2;
• R1 and R3 are independently C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl, wherein said alkyl or alkenyl is substituted with one or more substituent(s) independently selected from the group consisting of (Ar1)n, C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl substituted with (Ar1)n, C3-C8 cycloalkyl, C1-C6 straight or branched chain alkyl or C2-C6 straiqht or branched chain alkenyl substituted with C3-C8 cycloalkyl, and Ar2;
• n is 1 or 2;
• R2 is either C1-C9 straight or branched chain alkyl, C2-C9 straight or branched chain alkenyl, C3-C8 cycloalkyl, C5-C7 cycloalkenyl or Ar1, wherein said alkyl, alkenyl, cycloalkyl or cycloalkenyl is either unsubstituted or substituted with one or more substituent(s) independently selected from the group consisting of C1-C4 straight or branched chain alkyl, C2-C4 straight or branched chain alkenyl, and hydroxy;
• and
• Ar1 and Ar2 are independently an alicyclic or aromatic, mono-, bi- or tricyclic, carbo- or heterocyclic ring, wherein said ring is either unsubstituted or substituted with one or more substituent(s) independently selected from the group consisting of halo, hydroxy, nitro, trifluoromethyl, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, C1-C4 alkoxy, C2-C4 alkenyloxy, phenoxy, benzyloxy, and amino;
• wherein the individual ring size is 5-8 members;
• and wherein the heterocyclic ring has 1-6 heteroatom(s) independently selected from the group consisting of O, N, and S.