Small molecule inhibitors of rotamase enzyme activity

A non-immunosuppressive neurotrophic compound of the formula:

• where R1 is a C1-C9 straight or branched chain alkyl or alkenyl group optionally substituted with C3-C8 cycloalkyl, C3 or C5 cycloalkyl, C5-C7 cycloalkenyl, or Ar1, where said alkyl, alkenyl, cycloalkyl or cycloalkenyl groups may be optionally substituted with C1-C4 alkyl, C1-C4 alkenyl, or hydroxy, and where Ar1 is selected from the group consisting of 1-naphthyl, 2-naphthyl, 2-indolyl, 3-indolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-, 3-, or 4-pyridyl, or phenyl, having one to three substituents which are independently selected from the group consisting of hydrogen, halo, hydroxyl, nitro, trifluoromethyl, C1-C6 straight or branched alkyl or alkenyl, C1-C4 alkoxy or C1-C4 alkenyloxy, phenoxy, benzyloxy, and amino;
• X is selected from the group consisting of oxygen and sulfur;
• Y is oxygen or NR2, where R2 is hydrogen or C1-C6 alkyl;
• and
• Z is a C2-C6 straight or branched chain alkyl or alkenyl, wherein the alkyl chain is substituted in one or more positions with Ar1 as defined above, C3-C8 cycloalkyl, cycloalkyl connected by a C1-C6 straight or unbranched alkyl or alkenyl chain, or Ar2 where Ar2 is selected from the group consisting of 2-indolyl, 3-indolyl, 2-furyl, 3-furyl, 2-thiazolyl, 2-thienyl, 3-thienyl, 2-, 3-, or 4-pyridyl, or phenyl, having one to three substituents which are independently selected from the group consisting of hydrogen, halo, hydroxyl, nitro, trifluoromethyl, C1-C6 straight or branched alkyl or alkenyl, C1-C4 alkoxy or C1-C4 alkenyloxy, phenoxy, benzyloxy, and amino;
• Z may also be the fragment:
• where R3 is selected from the group consisting of straight or branched alkyl C1-C8 optionally substituted with C3-C8 cycloalkyl, or Ar1 as defined above;
• X2 is O or NR5, where R5 is selected from the group consisting of hydrogen, C1-C6 straight or branched alkyl and alkenyl;
• R4 is selected from the group consisting of phenyl, benzyl, C1-C5 straight or branched alkyl or alkenyl, and C1-C5 straight or branched alkyl or alkenyl substituted with phenyl;
• or pharmaceutically acceptable salts or hydrates thereof.