Patent ID: 6399648
Filing Date: 2002-06-04
Classification: A61K,A61P

Abstract:
A method for treating a nerve-related vision disorder, improving vision, treating memory impairment, or enhancing memory performance in an animal, which comprises administering to said animal an effective amount of an N-oxide of a heterocyclic ester, amide, thioester, or ketone compound, wherein the compound has an affinity for an FKBP-type immunophilin, wherein the FKBP-type immunophilin is FKBP-12, wherein the nerve-related vision disorder is selected from the group consisting of visual impairments, orbital disorders; disorders of the lacrimal apparatus; disorders of the eyelids; disorders of the conjunctiva; disorders of the cornea; cataract; disorders of the uveal tract; disorders of the retain; disorders of the optic nerve or visual pathways; free radical induced eye disorders and diseases; immunologically-mediated eye disorders and diseases; eye injuries; and symptoms and complications of eye disease, eye disorder, and eye injury, wherein the compound is of formula (I): or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein:A and B are taken together, with the nitrogen and carbon atoms to which they are respectively attached, to form a 5-7 membered saturated or unsaturated heterocyclic ring containing any combination of CH, CH2, O, S, SO, SO2, N, NH and NR1; W is O, S, CH2, or H2; R is C1-C6 straight or branched chain alkyl or a C2-C6 straight or branched chain alkenyl optionally substituted with C3-C8 cycloalkyl, C5-C7 cycloalkenyl, or Ar1, where said alkyl, alkenyl, cycloalkyl, or cycloalkenyl groups may be optionally substituted with C1-C4 alkyl, C2-C4 alkenyl, hydroxy, C3-C8 cycloalkyl, C5-C7 cycloalkenyl, or Ar2; Ar1 and Ar2 are independently selected from the group consisting of 1-naphthyl, 2-naphthyl, 1-indolyl, 2-indolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl and phenyl, having one or more substituent(s) independently selected from the group consisting of hydrogen, halo, hydroxy, nitro, trifluoromethyl, C1-C6 straight or branched chain alkyl, C2-C8 straight or branched chain alkenyl, C2-C4 alkenyloxy, phenoxy, benzyloxy, and amino; X is O, NH, NR1, S, CH, CR1, or CR1R3; Y is a direct bond, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl; wherein said alkyl or alkenyl is optionally substituted with one or more substituent(s) independently selected from the group consisting of C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, C3-C8 cycloalkyl, C5-C7 cycloalkenyl, hydroxy, carbonyl oxygen, and Ar; wherein said alkyl, alkenyl, cycloalkyl, cycloalkenyl, or Ar is optionally substituted with C1-C4 alkyl, C2-C4 alkenyl, hydroxy, or carbonyl oxygen; wherein any carbon atom of said alkyl, alkenyl, cycloalkyl, cycloalkenyl, or Ar is optionally replaced with O, NH, NR2, S, SO, or SO2; R2 is selected from the group consisting of hydrogen, C1-C4 straight or branched chain alkyl, C3-C4 straight or branched chain alkenyl or alkynyl, and C1-C4 bridging alkyl wherein a bridge is formed between the nitrogen and a carbon atom of said alkyl or alkenyl chain containing said heteroatom to form a ring, wherein said ring is optionally fused to an Ar group; Z is an aromatic or tertiary alkyl amine oxidized to a corresponding N-oxide, wherein the aromatic amine is Ar oxidized to a corresponding N-oxide where Ar is a mono-, bi-, or tricyclic, carbo- or heterocyclic ring, wherein the ring is either unsubstituted or substituted in one to three position(s) with 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, amino, or a combination thereof; wherein the individual ring sizes are 5-6 members; wherein the heterocyclic ring contains 1-6 heteroatom(s) selected from the group consisting of O, N, S, and a combination thereof wherein at least one of the heteroatoms is N, and where the alkyl amine is oxidized to a corresponding N-oxide where alkyl is a C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl which is optionally substituted in one or more positions with C1-C6 straight or branched chain alkyl or C2-C6 straight or branched chain alkenyl, C3-C8 cycloalkyl, C5-c7 cycloalkenyl, hydroxyl, carbonyl oxygen, or Ar wherein said alkyl, alkenyl, cycloalkyl, cycloalkenyl, or Ar group is optionally substituted with C1-C4 alkyl, C2-C4 alkenyl, hydroxy, or carbonyl oxygen; or wherein any of the carbon atoms of said alkyl, alkenyl, cycloalkyl, cycloalkenyl, or Ar group is optionally replaced with O, NH, NR2, S, SO, or SO2; Ar is selected from the group consisting of pyrrolidinyl, pyridyl, pyrimidyl, pyrazyl, pyridazyl, quinolinyl, and isoquinolinyl; and R1 and R2 are independently hydrogen, C1-C4 straight or branched chain alkyl, C3-C4 straight or branched chain alkenyl or alkynyl, or Y-Z.