Patent ID: 6395758
Filing Date: 2002-05-28
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 in need thereof, which comprises administering to said animal an effective amount of a heterocyclic compound, wherein the compound is of formula I or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein:A is CH2, O, NH or Nâ€”(C1-C4 alkyl); B and D are independently Ar, hydrogen, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl or alkynyl, C5-C7 cycloalkyl substituted C1-C6 straight or branched chain alkyl or C3-C6 straight or branched chain alkenyl or alkynyl, C5-C7 cycloalkenyl substituted C1-C6 straight or branched chain alkyl or C3-C6 straight or branched chain alkenyl or alkynyl, Ar substituted C1-C6 straight or branched chain alkyl, or Ar substituted C3-C6 straight or branched chain alkenyl or alkynyl; wherein any carbon atom of said alkyl or alkenyl is optionally replaced by a heteroatom selected from the group consisting of O, S, SO, SO2 and NR, wherein R 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 heteroatom-containing chain to form a ring, and wherein said ring is optionally fused to an Ar group; J is selected from the group consisting of hydrogen, C1-C6 straight or branched chain alkyl, C3-C6 straight or branched chain alkenyl, and â€”CH2Ar; K is selected from the group consisting of C1-C4 straight or branched chain alkyl, â€”CH2Ar, and cyclohexylmethyl; or J and K are taken together to form a 5-7 membered heterocyclic ring which may contain one or more heteroatoms selected from the group consisting of O, S, SO, and SO2; Z is O, S, two hydrogen atoms, or CH2; Y is O or N, provided that when Y is O, then R1 is a lone pair of electrons and R2 is selected from the group consisting of Ar, C1-C6 straight or branched chain alkyl, and C3-C6 straight or branched chain alkenyl or alkynyl; and when Y is N, then R1 and R2 are independently selected from the group consisting of Ar, C1-C6 straight or branched chain alkyl, and C3-C6 straight or branched chain alkenyl or alkynyl; or R1 and R2 are taken together to form a heterocyclic 5-6 membered ring selected from the group consisting of pyrrolidine, imidazolidine, pyrazolidine, piperidine, and piperazine; Ar is independently a carbocyclic aromatic group selected from the group consisting of phenyl, 1-naphthyl, 2-naphthyl, indenyl, azulenyl, fluorenyl, and anthracenyl; or Ar is independently a heterocyclic aromatic group selected from the group consisting of 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyraxolyl, 2-pyrazolinyl, pyrazolidinyl, isoxazolyl, isotriazolyl, 1,2,3-oxadiazolyl, 1,2,3-triazolyl, 1,3,4-thiadiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazinyl, 1,3,5-trithianyl, indolizinyl, indolyl, isoindolyl, 3H-indolyl, indolinyl, benzo[b]furanyl, benzo[b]thio-phenyl, 1H-indazolyl, benzimidazolyl, benzthiazolyl, purinyl, 4H-quinolizinyl, quinolinyl, 1,2,3,4-tetrahydroquinolinyl, isoquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, and phenoxazinyl, wherein said Ar is unsubstituted or substituted with one or more substituent(s) independently selected from the group consisting of hydrogen, halogen, hydroxy, nitro, â€”SO3H, trifluoromethyl, trifluoromethoxy, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, Oâ€”(C1-C6 straight or branched chain alkyl), Oâ€”(C3-C4 straight or branched chain alkenyl), O-benzyl, O-phenyl, 1,2-methylenedioxy, â€”NR3R4, carboxyl, Nâ€”(C1-C5 straight or branched chain alkyl or C3-C5 straight or branched chain alkenyl) carboxamides, N,N-di-(C1-C5 straight or branched chain alkyl or C3-C5 straight or branched chain alkenyl) carboxamides, morpholinyl, piperidinyl, Oâ€”X, CH2â€”(CH2)qâ€”X, Oâ€”(CH2)qâ€”X, (CH2)1â€”Oâ€”X, and CH&boxH;CHâ€”X; R3 and R4 are independently selected from the group consisting of C1-C6 straight or branched chain alkyl, C3-C6 straight or branched chain alkenyl, hydrogen, and benzyl; or R3 and R1 are taken together to form a 5-6 membered heterocyclic ring; X is selected from the group consisting of 4-methoxyphenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrazyl, quinolyl, 3,5-dimethylisoxazoyl, isoxazoyl, 2-methylthiazoyl, thiazoyl, 2-thienyl, 3-thienyl, and pyrimidyl; q is 0-2; and n is 0 or 1; 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 retina; 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.