N-linked sulfonamide of heterocyclic thioesters for vision and memory disorders

A method for treating a nerve-related vision disorder, improving vision in a mammal in need thereof, which comprises administering to said animal an effective amount of an N-linked sulfonamide of a compound of formula V:

• or a pharmaceutically acceptable salt, ester, or solvate thereof, wherein:
• V is C, N, or S;
• A and B, taken together with the nitrogen and carbon atoms to which they are respectively attached, form a 5-7 membered saturated or unsaturated heterocyclic ring containing any combination of CH2, O, S, SO, SO2, N, NH, or NR2 in any chemically stable oxidation state;
• X is either O or S;
• Y is a direct bond, C1-C6 straight or branched chains alkyl, or C2-C6 straight or branched chain alkenyl,
• wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, sulfonyl, or oxygen to form a carbonyl,
• or wherein any carbon atom of said alkyl or alkenyl 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 Q-C4 bridging alkyl,
• wherein a bridge is formed between the nitrogen and a carbon atom of said alkyl or alkenyl chain containing said heteroatom for form a ring,
• wherein said ring is optionally fused to an Ar group;
• Ar is an alicyclic or aromatic, mono-, bi- or tricyclic, carbo- or heterocyclic ring,
• wherein the ring is either unsubstituted or substituted with one or more substituent(s),
• wherein the individual ring size is 5-8 members,
• wherein the heterocyclic ring contains 1-6 heteroatom(s) independently selected from the group consisting of O, N, and S,
• and wherein an aromatic or tertiary alkyl amine is optionally oxidized to a corresponding N-oxide;
• Z is a direct bond, C1-C6 straight or branched chain alkyl, or C2-C6 straight or branched chain alkenyl,
• wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, sulfonyl, or oxygen to form a carbonyl,
• or wherein any atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2;
• C and D are independently hydrogen, Ar, 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 C3-C8 cycloalkyl, C5-C7;
• cycloalkenyl, hydroxy, carbonyl oxygen, Ar, C1-C6 alkyl, C2-C6 alkenyl, hydroxy, amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, and sulfonyl,
• wherein said cycloalkyl or cycloalkenyl is optionally substituted with C1-C6 alkyl, C2-C6 alkenyl, hydroxy, amino, halo, haloalkyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, or sulfonyl,
• wherein any carbon atom of said alkyl or alkenyl is optionally substituted in one or more position(s) with oxygen to form a carbonyl,
• or wherein any carbon atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2;
• and
• R1 is selected from the group consisting of Ar, C3-C8 cycloalkyl, C1-C6 straight or branched chain alkyl, and 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 Ar, C3-C8 cycloalkyl, amino, halo, haloalkyl, hydroxy, trifluoromenthyl, C1-C6 straight or branched chain alkyl, C2-C6 straight or branched chain alkenyl, carbonyl, thiocarbonyl, ester, thioester, alkoxy, alkenoxy, cyano, nitro, imino, alkylamino, aminoalkyl, sulfhydryl, thioalkyl, and sulfonyl,
• or wherein any carbon atom of said alkyl or alkenyl is optionally replaced with O, NH, NR2, S, SO, or SO2,
• 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.