| abstract |
The neurotrophic low molecular weight, small molecule heterocyclic thioesters and ketones of formula II have an affinity for FKBP-type immunophilins and may be used as inhibitors of the enzyme activity associated with immunophilin proteins, particularly peptidyl-prolyl isomerase or rotamase enzyme activity. The compounds may be used in medicaments to stimulate damaged neurons, promote neuronal regeneration, prevent neurodegeneration, and treat Alzheimer's Disease, Parkinson's Disease and amyotrophic lateral sclerosis. In formula II; n is 1 or 2; X is O or S; Z is selected from S, CH2, CHR1 and C(R1)2; R1 is selected from the group consisting of C1-C5 straight or branched chain alkyl, C2-C5 straight or branched chain alkenyl, Ar1 and mixtures thereof, wherein said R1 is unsubstituted or substituted with 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, Ar1 or a mixture thereof; R2 is selected from the group consisting of C1-C9 straight or branched chain alkyl, C2-C9 straight or branched chain alkenyl, C3-C9 cycloalkyl, C5-C7 cycloalkenyl and Ar1; and Ar1 is phenyl, benzyl, pyridyl, fluorenyl, thioindolyl or naphthyl wherein said Ar1 is unsubstituted or substituted with halo, hydroxy, nitro, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, C1-C4 alkoxy, C2-C4 alkenyloxy, phenoxy, benzyloxy, amino or a mixture thereof. |