Small molecule pipecolic acid derivative 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 II

• or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein:
• A is O, NH, or N—(C1-C4 alkyl);
• B is hydrogen, CHL—Ar, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, C5-C7 cycloalkyl, C5-C7 cycloalkenyl, Ar substituted C1-C6 alkyl or C2-C6 alkenyl, or
• wherein L and Q are independently hydrogen, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl;
• and
• T is Ar or C5-C7 cyclohexyl substituted at positions 3 and 4 with substituents independently selected from the group consisting of hydrogen, hydroxy, O—(C1-C4 alkyl), O—(C2-C4 alkenyl), and carbonyl;
• Ar is selected from the group consisting of 1-napthyl, 2-napthyl, 2-furyl, 3-furyl, 2-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl and phenyl having 1-3 substituent(s) independently selected from the group consisting of hydrogen, halo, hydroxy, nitro, CF3, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, O—(C1-C4 straight or branched chain alkyl), O—(C2-C4 straight or branched chain alkenyl), O-benzyl, O-phenyl, amino, and phenyl.
• D is hydrogen or U;
• E is oxygen or CH—U, provided that if D is hydrogen, then E is CH—U, or if E is oxygen, then D is U;
• U is hydrogen, O—(C1-C4 straight or branched chain alkyl), O-(C2-C4 straight or branched chain alkenyl), C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, C5-C7-cycloalkyl, C5-C7 cycloalkenyl substituted with C1-C4 straight or branched chain alkyl or C2-C4 straight or branched chain alkenyl, 2-indolyl, 3-indolyl, (C1-C4 alkyl or C2-C4 alkenyl)-Ar, or Ar;
• J is hydrogen, C1 or C2 alkyl, or benzyl;
• K is C1-C4 straight or branched chain alkyl, benzyl or cyclohexylethyl;
• or J and K are taken together to form a 7 membered heterocyclic ring which is substituted with oxygen, sulfur, SO, or SO2;
• and
• said compound has an affinity for FKBP-type immunophilins.

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 IV

• or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein:
• V is C, N, or S;
• J and K, taken together with V and the carbon atom to which they are respectively attached, form a 7 membered saturated or unsaturated heterocyclic ring having, in addition to V, one or more heteroatom(s) selected from the group consisting of O, S, SO, SO2, N, NH, and NR;
• R is either C1-C9 straight or branched chain alkyl, C2-C9 straight or branched chain alkenyl, C3-C9 cycloakyl, C5-C7 cycloalkenyl, or Ar1, wherein R is either unsubstituted of 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 Ar2;
• Ar1 and Ar2 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;
• A is O, NH, or N—(C1-C4 alkyl);
• B and D are independently Ar, C5-C7 cycloalkyl substituted C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl, C5-C7 cycloalkenyl substituted C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl, or Ar substituted C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl, wherein in each case, one or two carbon atom(s) of said alkyl or alkenyl is/are optionally substituted with one or two heteroatom(s) independently selected from the group consisting of oxygen, sulfur, SO, and SO2, or
• wherein O is hydrogen, C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl;
• and
• T is Ar or C5-C7 cycloalkyl substituted at positions 3 and 4 with substituents independently selected from the group consisting of hydrogen, hydroxy, O—(C1-C4 alkyl), O—(C2-C4 alkenyl), and carbonyl;
• Ar is selected from the group consisting of 1-napthyl, 2-napthyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl and phenyl, monocyclic and bicyclic heterocyclic ring systems with individual ring sizes being 5 or 6 which have in either or both rings a total of 1-4 heteroatoms independently selected from oxygen, nitrogen and sulfur;
• wherein Ar has 1-3 substituent(s) independently selected from the group consisting of hydrogen, halo, hydroxy, hydroxymethyl, nitro, CF3, trifluoromethoxy, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, O—(C1C4 straight or branched chain alkyl), O—(C2-C4 straight or branched chain alkenyl), O-benzyl, O-phenyl, amino, 1,2-methylenedioxy, carbonyl, and phenyl;
• L is either hydrogen or U;
• M is either oxygen or CH—U, provided that if L is hydrogen, then M is CH—U, or if M is oxygen then L is U;
• U is hydrogen, O—(C1-C4 straight or branched chain alkyl), O—(C2-C4 straight or branched chain alkenyl), C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, C5-C7 cycloalkyl, C5-C7 cycloalkenyl substituted with C1-C4 straight or branched chain alkyl or C2-C4 straight or branched chain alkenyl, (C1-C4 alkyl or C2-C4 alkenyl)-Ar, or Ar;
• m is 0-3;
• and
• said compound has an affinity for FKBP-type immunophilins.