Compositions and Methods for Treating Ophthalmic Diseases

1 . Use of a compound of structural formula I for the manufacture of a medicament for treating ocular disorders in a patient in need of such treatment:

or a pharmaceutically acceptable salt, prodrug and/or hydrate thereof,

wherein

Z represents an optionally substituted five-membered heteroaromatic ring selected from furan, thiophenyl, pyrrolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl and tetrazolyl;

E represents a chemical bond or a straight or branched alkylene chain containing from 1 to 4 carbon atoms;

Q represents a straight or branched alkylene chain containing from 1 to 4 carbon atoms, optionally substituted in any position by a hydroxy group;

T represents nitrogen or CH;

U represents nitrogen or C—R 2 ;

V represents oxygen, sulphur or N—R 3 ;

R 2 and R 3 independently represent hydrogen or C 1-6 alkyl;

M represents the residue of an azetidine, pyrrolidine or piperidine ring;

R represents a group of formula —W—R 1 ;

W represents a chemical bond or a straight or branched alkylene chain containing from 1 to 4 carbon atoms, optionally substituted in any position by a hydroxy group;

R 1 represents —OR x , —SR x , —SOR x , —SO 2 R x or —NR x R y ;

R x and R y independently represent hydrogen, hydrocarbon or a heterocyclic group; or R x and R y together represent a C 2-6 alkylene group, which alkylene group may be optionally substituted by one or more substituents selected from C 1-6 alkyl, aryl and hydroxy, or fused with a phenyl ring; and

R a represents hydrogen, hydroxy, hydrocarbon or a heterocyclic group.

2 . The use according to claim 1 wherein the ocular disorder is macular degeneration, diabetic retinopathy, or macular edema.

3 . The use according to claim 2 wherein the macular degeneration is neovascular AMD or geographic atrophy, and the diabetic retinopathy is proliferative diabetic retinopathy.

4 . The use according to claim 1 wherein the compound of formula I is:

(3R)-3-benzyloxy-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3R)-3-(4-methoxyphenyl)methoxy-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3R)-3-benzyloxymethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-(N-benzyl-N-methyl)aminomethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(2S)-2-(N-benzyl-N-methyl)aminomethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-(N-benzyl)aminomethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

4-(4-acetylaminophenyl)methylamino-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

4-benzylamino-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

4-(N-benzyl-N-methyl)amino-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

4-(N-benzyl)aminomethyl-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

(2S)-2-(N-benzyl-N-methylaminomethyl)-1-[2-(5-(1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)ethyl]pyrrolidine;

4-(N-benzyl-N-methyl)aminomethyl-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(R)-α-(methyl)benzylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(S)-α-(methyl)benzylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(S)-α-(hydroxymethyl)benzylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(R)-α-(hydroxymethyl)benzylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(S)-(1-hydroxymethyl-2-phenyl)ethylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(1R,2S)-(2-hydroxy-1-methyl-2-phenyl)ethylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(1S,2R)-(2-hydroxy-1-methyl-2-phenyl)ethylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(1R,2R)-(2-hydroxy-1-methyl-2-phenyl)ethylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[2-(4-acetylaminophenyl)ethylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(R)-α-(methyl)benzylamino]methylpiperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(S)-1-(methyl)benzylamino]methylpiperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(S)-1-(4-acetylaminophenyl)ethylamino]methylpiperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(R)-1-(4-acetylaminophenyl)ethylamino]methylpiperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[N—[(R)-α-(hydroxymethyl)benzyl]-N-methylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[N—[(S)-α-(hydroxymethyl)benzyl]-N-methylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[N-(2-(4-acetylaminophenyl)ethyl)-N-methylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[N-(4-acetylaminobenzyl)-N-methylamino]methyl piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(R)-α-(hydroxymethyl)benzylamino]methyl piperidine;

(3S)-3-(4-acetylaminobenzyl)aminomethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3R)-3-(N-benzyl)aminomethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

3-(N-benzyl)aminomethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]azetidine;

4-benzyl-4-hydroxy-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

3-(N-benzyl)aminomethyl-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]azetidine;

4-(N-benzyl)aminomethyl-4-hydroxyl-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

4-(N-benzyl-N-methyl)aminomethyl-4-hydroxy-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

3-(N-benzyl-N-methyl)aminomethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]azetidine;

(3S)-3-[N—(R)-(x-(methyl)benzyl]aminomethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-[N—(S)-α-(methyl)benzyl]aminomethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-[N—(R)-α-(hydroxymethyl)benzyl]aminomethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-[N—(S)-α-(hydroxymethyl)benzyl]aminomethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-[N-benzyl-N-(2-hydroxy)ethyl]aminomethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-[N-(2-phenylethyl)amino]methyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-[N-(2-phenylethyl)-N-methylamino]methyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-(N-x-dimethylbenzyl)aminomethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-[N—(S)-α-methylbenzyl]aminomethyl-1-[2-(5-(1,2,4-triazol-1-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-[N—(R)-α-(hydroxymethyl)benzyl]aminomethyl-1-[2-(5-(1,2,4-triazol-1-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-(N-benzyl)aminomethyl-1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-[N—(S)-α-methylbenzyl]aminomethyl-1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-[N—(R)-α-(hydroxymethyl)benzyl]aminomethyl-1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-(N-benzyl-N-methyl)aminomethyl-1-[2-(5-(imidazol-1-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-(N-benzyl-N-methyl)aminomethyl-1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3R)-3-[N-methyl-N—(S)-α-methylbenzyl]aminomethyl-1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3R)-3-[N-methyl-N—(R)-α-hydroxymethylbenzyl]aminomethyl-1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3R)-3-[N-methyl-N—(S)-α-methylcyclohexylmethyl]aminomethyl-1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3R)-3-[3-(R)-hydroxy-2-(R)-phenylpiperidin-1-yl]methyl-1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3R)-3-[3-(R)-hydroxy-2-(R)-phenylpiperidin-1-yl]methyl-1-[2-(5-(1,2,4-triazol-1-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

4-hydroxy-4-(phenylsulfinyl)methyl-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

(3R)-3-[2-(R,S)-phenylpiperidin-1-yl]methyl 1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine;

4-(3,3-dimethylpiperidin-1-yl)methyl-4-hydroxy-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

4-hydroxy-4-(1,2,3,4-tetrahydroisoquinolin-2-yl)methyl-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

4-hydroxy-4-(N-isobutyl-N-methyl)aminomethyl-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

4-[N-benzyl-N-(2-hydroxyethyl)amino]methyl-4-hydroxy-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

4-[N-(2,2-dimethylpropyl)-N-methylamino]methyl-4-hydroxy-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

4-[N—(R)-α-hydroxymethylbenzyl-N-methylamino]methyl-4-hydroxy-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

4-hydroxy-4-(2-methylphenylmethyl)aminomethyl-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

4-hydroxy-4-[N-(2-methylphenylmethyl)-N-methylamino]methyl-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

3-(benzylamino)methyl-3-hydroxy-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]pyrrolidine;

3-(benzylamino)methyl-3-hydroxy-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(R)-α-(carbamoyl-oxymethyl)benzylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(1R,2S)-2-hydroxy-1-phenylpropylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(1R,2R)-2-hydroxy-1-phenylpropylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(R,S)-1-hydroxy-2-phenylprop-2-ylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(R)-2-hydroxy-1-(4-fluorophenyl)ethylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(1R,2R)-2-hydroxyindan-1-ylamino)piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(R,S)-indan-1-ylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(R,S)-1-(4-fluorophenyl)ethylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(R)-1-phenylprop-2-ylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[N-(3,3-dimethylallyl)-N-methyl o]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-(N-allyl-N-methylamino)piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-(indan-1-ylaminomethyl)piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[N—(R)-α-(hydroxymethyl)benzyl-N-methylaminomethyl]piperidine;

(3R)-3-(benzylthio)methyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(±)-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-(1-benzylamino-2-hydroxyethyl)piperidine;

1-[3-(5-(1,2,4-triazol-1-yl)-1H-indol-3-yl)propyl]-4-[(R)-α-(hydroxymethyl)benzylamino]piperidine;

1-[3-(5-(imidazol-1-yl)-1H-indol-3-yl)propyl]-4-[(R)-α-(methyl)benzylamino]piperidine;

1-[3-(5-(imidazol-1-yl)-1H-indol-3-yl)propyl]-4-[(R)-α-(hydroxymethyl)benzylamino]piperidine;

1-[3-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)propyl]-4-[(R)-α-(hydroxymethyl)benzylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(R)-α-(methoxymethyl)benzylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[N—(R)-α-(methoxymethyl)benzyl-N-methylamino]piperidine;

1-[3-(5-(imidazol-1-yl)-1H-indol-3-yl)propyl]-4-[(R)-α-(methoxymethyl)benzylamino]piperidine;

1-[3-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)propyl]-4-[(R)-1-(4-fluorophenyl)-2-methoxyethylamino]piperidine;

1-[3-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)propyl]-4-[N-(4-fluorobenzyl)-N-methylamino]piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-(2-phenylpiperidin-1-yl)piperidine;

1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]-4-[(R)-1-(4-fluorophenyl)-2-methoxyethylamino]piperidine;

(3R)-3-(benzylsulfinyl)methyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3R)-3-(4-fluorobenzylthio)methyl-1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3R)-3-(4-fluorobenzylsulfinyl)methyl-1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3R)-3-(4-fluorobenzylsulfonyl)methyl-1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine;

4-(4-fluorobenzylsulfinyl)-1-[3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine;

and pharmaceutically acceptable salts, prodrugs, and/or hydrates thereof.

5 . The use according to claim 4 wherein the compound of formula I is:

(3S)-3-[N-(2-phenylethyl)amino]methyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-[N-(2-phenylethyl)-N-methylamino]methyl 1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-(N-α-dimethylbenzyl)aminomethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-[N—(S)-α-methylbenzyl]aminomethyl-1-[2-(5-(1,2,4-triazol-1-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-[N—(R)-(x-(hydroxymethyl)benzyl]aminomethyl-1-[2-(5-(1,2,4-triazol-1-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-(N-benzyl)aminomethyl-1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-[N—(S)-α-methylbenzyl]aminomethyl-1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-[N—(R)-α-(hydroxymethyl)benzyl]aminomethyl-1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-(N-benzyl-N-methyl)aminomethyl-1-[2-(5-(imidazol-1-yl)-1H-indol-3-yl)ethyl]pyrrolidine;

(3S)-3-(N-benzyl-N-methyl)aminomethyl-1-[2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl)ethyl]pyrrolidine; and salts and prodrugs thereof.

and pharmaceutically acceptable salts, prodrugs, and/or hydrates thereof.

6 . The use according to claim 5 wherein the compound is (3S)-3-(N-α-dimethylbenzyl)aminomethyl-1-[2-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)ethyl]pyrrolidine

7 . Use of a compound of claim 1 for the manufacture of a medicament for the treatment of diabetic retinopathy, corneal neovascularization or iris neovascularization in a patient in need of such treatment.