Amido thiadiazole derivatives as nadph oxidase inhibitors

Abstract

The present invention is related to amino thiazole derivatives of Formula (I), pharmaceutical composition thereof and to their use for the treatment and/or prophylaxis of disorders or conditions related to Nicotinamide adenine dinucleotide phosphate oxidase (NADPH Oxidase).

We claim: 
     
         1 . A method for treating a patient suffering from a disease or condition selected from cardiovascular disorders, respiratory disorders, metabolic disorders, skin disorders, bone disorders, neuroinflammatory and/or neurodegenerative disorders, kidney diseases, reproduction disorders, diseases affecting the eye and/or the lens and/or conditions affecting the inner ear, inflammatory disorders, liver diseases, pain, cancers, fibrotic disorders, psychotic disorders, infectious diseases, allergic disorders, traumatisms, septic, hemorrhagic and anaphylactic shock, diseases or disorders of the gastrointestinal system, angiogenesis and angiogenesis-dependent and other diseases and/or disorders associated with Nicotinamide adenine dinucleotide phosphate oxidase (NADPH Oxidase), said method comprising administering an amido thiadiazole derivative according to Formula (I) to a patient in need thereof 
       
         
           
           
               
               
           
         
       
       wherein X is selected from CR 1  and N; Y is selected from CH or N; A 1  is selected from —OCHR 5 —, —NR 4 —CHR 5 —, —CH 2 NR 4 — and —CH 2 —O—; R 1  is selected from H, halogen and optionally substituted C 1 -C 6  alkyl; R 2  is selected from H, halogen, optionally substituted alkoxy, optionally substituted alkoxy C 1 -C 6  alkyl, optionally substituted C 1 -C 6  alkyl, optionally substituted amino, optionally substituted C 1 -C 6  alkyl amino, optionally substituted heterocycloalkyl, optionally substituted C 1 -C 6  alkyl heterocycloalkyl, optionally substituted amino C 1 -C 6  alkyl, optionally substituted alkoxy C 1 -C 6  alkyl, —O—R 8  and —NR 9 R 10 ; R 3  is a group of formula —(CHR 6 ) n A 2  or R 3  forms with the moiety CHR 5  from A 1  an optionally substituted ring selected from optionally substituted aryl and optionally substituted heteroaryl, or R 3  forms with the moiety NR 4  from A 1  an optionally substituted ring selected from optionally substituted aryl, optionally substituted heteroaryl; n is an integer from 0 to 4; R 4  is selected from H and optionally substituted alkyl; A 2  is an optionally substituted ring selected from optionally substituted aryl and optionally substituted heteroaryl; R 5  is selected from H, optionally substituted C 1 -C 6  alkyl, optionally substituted amino C 1 -C 6  alkyl, optionally substituted alkoxy C 1 -C 6  alkyl, optionally substituted heterocycloalkyl C 1 -C 6  alkyl, optionally substituted aminocarbonyl, optionally substituted C 2 -C 8  cycloalkyl and optionally substituted amino C 1 -C 6  alkyl; R 6  is selected from H, optionally substituted C 1 -C 6  alkyl, optionally substituted amino, optionally substituted C 1 -C 6  alkyl amino and hydroxy and wherein R 6  groups are independently selected for each repeating unit (CHR 6 ); R 7  is selected from H, halogen and optionally substituted C 1 -C 6  alkyl; R 8  is selected from H, optionally substituted C 1 -C 6  alkyl, optionally substituted amino C 1 -C 6  alkyl, optionally substituted heterocycloalkyl, optionally substituted C 2 -C 8  cycloalkyl, optionally substituted heterocycloalkyl C 1 -C 6  alkyl, optionally substituted C 2 -C 8  cycloalkyl C 1 -C 6  alkyl, optionally substituted alkoxy, optionally substituted amino C 1 -C 6  alkyl; optionally substituted aryl C 1 -C 6  alkyl and optionally substituted heteroaryl C 1 -C 6  alkyl; R 9  and R 10  are independently selected from H, optionally substituted C 1 -C 6  alkyl, optionally substituted amino C 1 -C 6  alkyl, optionally substituted heterocycloalkyl, optionally substituted C 2 -C 8  cycloalkyl, optionally substituted heterocycloalkyl C 1 -C 6  alkyl, optionally substituted C 2 -C 8  cycloalkyl C 1 -C 6  alkyl, optionally substituted alkoxy, optionally substituted alkoxy C 1 -C 6  alkyl, optionally substituted aryl C 1 -C 6  alkyl and optionally substituted heteroaryl C 1 -C 6  alkyl, optionally substituted amino C 1 -C 6  alkyl; as well as tautomers, geometrical isomers, optically active forms, pharmaceutically acceptable salts and a pharmaceutical formulation thereof. 
     
     
         2 . The method according to  claim 1 , wherein X is N. 
     
     
         3 . The method according to  claim 1 , wherein X is CR 1 . 
     
     
         4 . The method according to  claim 1 , wherein Y is CH. 
     
     
         5 . The method according to  claim 1 , wherein Y is N. 
     
     
         6 . The method according to  claim 1 , wherein A 1  is —OCHR 5 —. 
     
     
         7 . The method according to  claim 1 , wherein A 1  is —NR 4 —CHR 5 . 
     
     
         8 . The method according to  claim 1 , wherein A 1  is —CH 2 NR 4 . 
     
     
         9 . The method according to  claim 1 , wherein A 1  is —CH 2 —O—. 
     
     
         10 . The method according to  claim 1 , wherein n is selected from 0, 1 and 2. 
     
     
         11 . The method according to  claim 1  selected from the following group:
 4-(1-phenylethoxy)-3-(piperidin-4-ylmethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-(2-hydroxyethoxy)-4-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) benzamide; 
 5-chloro-6-(2-(dimethylamino)-1-(pyridin-2-yl)ethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 3-methoxy-4-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-(1-(pyridin-2-yl)ethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) benzamide; 
 4-(2-(dimethylamino)-1-phenylethoxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-(2-hydroxy-1-phenylethoxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) benzamide; 
 4-(3-hydroxy-1-phenylpropoxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-(1-phenyl-3-(pyrrolidin-1-yl)propoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-(1-phenyl-2-(pyrrolidin-1-yl)ethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-(3-(dimethylamino)-1-phenylpropoxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-(2-(methylamino)-1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-(1-(pyridin-3-yl)ethoxy)-N-(5-(pyrimidin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 N-(5-(3-fluoropyridin-4-yl)-1,3,4-thiadiazol-2-yl)-3-methoxy-4-(1-(pyridin-3-yl)ethoxy)benzamide; 
 3-methoxy-N-(5-(3-methylpyridin-4-yl)-1,3,4-thiadiazol-2-yl)-4-(1-phenylethoxy)benzamide; 
 3-methoxy-N-(5-(2-methylpyridin-4-yl)-1,3,4-thiadiazol-2-yl)-4-(1-phenylethoxy)benzamide; 
 4-((1H-imidazol-4-yl)methoxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)-4-(pyrimidin-2-ylmethoxy) benzamide; 
 3-methoxy-4-((1-methyl-1H-imidazol-2-yl)methoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 5-methyl-6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-chloro-6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-((2-methoxyethyl)amino)-6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(benzyloxy)-5-chloro-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(benzyloxy)-5-(4-methylpiperazin-1-yl)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 5-methoxy-6-((1-phenylethyl)amino)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(3-(dimethylamino)-1-phenylpropoxy)-5-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(2-hydroxy-1-phenylethoxy)-5-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(2-hydroxy-2-phenylethoxy)-5-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-chloro-6-(2-hydroxy-2-methyl-1-phenylpropoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-chloro-6-(2-(dimethylamino)-1-(pyridin-2-yl)ethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(2-(dimethylamino)-1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 6-((1-(dimethylamino)-2,3-dihydro-1H-inden-2-yl)oxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-((1-(dimethylamino)-3-phenylpropan-2-yl)oxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-((1-phenylpropan-2-yl)oxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(1-(pyridin-3-yl)ethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-((1-(pyridin-3-yl)ethyl)amino)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)-5-((tetrahydro-2H-pyran-4-yl)methoxy)nicotinamide; 
 6-(3-morpholino-1-phenylpropoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 6-(2-morpholino-1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 4-(isoindolin-2-ylmethyl)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) benzamide; 
 6-(benzyloxy)-5-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-methoxy-6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 2-methyl-6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 2-methyl-6-(1-(pyridin-2-yl)ethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 6-(benzyloxy)-2-methyl-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-methoxy-6-(1-(pyridin-2-yl)ethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 5-chloro-6-(1-(pyridin-2-yl)ethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 6-(benzyloxy)-5-((2-(dimethylamino)ethyl)amino)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(benzyloxy)-5-methyl-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-((2-(dimethylamino)ethyl)amino)-6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)-5-(((tetrahydro-2H-pyran-4-yl)methyl)amino)nicotinamide; 
 5-(((1-methylpiperidin-4-yl)methyl)amino)-6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-(methylamino)-6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 6-(benzyloxy)-5-(methylamino)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(3-(dimethylamino)-1-phenylpropoxy)-5-methyl-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-chloro-6-(3-(dimethylamino)-1-phenylpropoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(2-(dimethylamino)-1-phenylethoxy)-5-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-chloro-6-(2-(dimethylamino)-1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(2-(dimethylamino)-1-phenylethoxy)-5-methyl-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-((3-(dimethylamino)propyl)amino)-6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-((2-hydroxyethyl)amino)-6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-(((1-methyl-1H-imidazol-4-yl)methyl)amino)-6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-((1-methylpiperidin-4-yl)amino)-6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-((2-morpholinoethyl)amino)-6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-(4-methylpiperazin-1-yl)-6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-(dimethylamino)-6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-methoxy-6-((1-(pyridin-3-yl)ethyl)amino)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(2-(dimethylamino)-1-(pyridin-2-yl)ethoxy)-5-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-(dimethylamino)-6-(3-(dimethylamino)-1-phenylpropoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(3-(dimethylamino)-1-phenylpropoxy)-5-(methylamino)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)-4-(pyridin-4-ylmethoxy)benzamide; 
 3-methoxy-4-(1-(pyridin-3-yl)ethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-((1,3-dimethyl-1H-pyrazol-5-yl)methoxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-((2,3-dihydro-1H-inden-1-yl)oxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)-4-((1,2,3,4-tetrahydronaphthalen-1-yl)oxy)benzamide; 
 3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)-4-(thiazol-4-ylmethoxy) benzamide; 
 3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)-4-(thiazol-2-ylmethoxy) benzamide; 
 3-(2-(dimethylamino)ethoxy)-4-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-(2-methoxyethoxy)-4-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) benzamide; 
 3-((1-methylpiperidin-4-yl)methoxy)-4-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-((2-methylpyridin-3-yl)methoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-((5-methylpyridin-2-yl)methoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-((5-methylisoxazol-3-yl)methoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-((4-methoxybenzyl)oxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) benzamide; 
 4-((2-fluorobenzyl)oxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) benzamide; 
 3-methoxy-4-(pyridin-2-ylmethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) benzamide; 
 4-((4-fluorobenzyl)oxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) benzamide; 
 3-methoxy-4-((5-methyl-1,2,4-oxadiazol-3-yl)methoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-((5-cyclopropylisoxazol-3-yl)methoxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-((1-methyl-1H-1,2,4-triazol-5-yl)methoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-((1-methyl-1H-imidazol-5-yl)methoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-(2-(1-methyl-1H-imidazol-2-yl)ethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-(1-(pyridin-2-yl)ethoxy)-N-(5-(pyrimidin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 N-(5-(3-fluoropyridin-4-yl)-1,3,4-thiadiazol-2-yl)-3-methoxy-4-(1-(pyridin-2-yl) ethoxy)benzamide; 
 N-(5-(3-fluoropyridin-4-yl)-1,3,4-thiadiazol-2-yl)-4-(3-hydroxy-1-phenylpropoxy)-3-methoxybenzamide; 
 N-(5-(3-fluoropyridin-4-yl)-1,3,4-thiadiazol-2-yl)-4-(2-hydroxy-1-phenylethoxy)-3-methoxybenzamide; 
 4-(2-(dimethylamino)-1-phenylethoxy)-N-(5-(3-fluoropyridin-4-yl)-1,3,4-thiadiazol-2-yl)-3-methoxybenzamide; 
 6-(3-(dimethylamino)-1-phenylpropoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)-5-((tetrahydro-2H-pyran-4-yl)methoxy)nicotinamide; 
 5-chloro-6-(2-hydroxy-1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 4-(3-hydroxy-1-phenylpropoxy)-3-methoxy-N-(5-(pyrimidin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-(2-hydroxy-1-phenylethoxy)-3-methoxy-N-(5-(pyrimidin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-(benzyloxy)-3-methoxy-N-(5-(pyrimidin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-(benzyloxy)-N-(5-(3-fluoropyridin-4-yl)-1,3,4-thiadiazol-2-yl)-3-methoxybenzamide; 
 4-(2-(dimethylamino)-1-phenylethoxy)-3-methoxy-N-(5-(3-methylpyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 6-(2-(dimethylamino)-1-phenylethoxy)-5-methoxy-N-(5-(pyrimidin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 4-(2-(dimethylamino)-1-phenylethoxy)-3-methoxy-N-(5-(2-methylpyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-((1-phenylpropan-2-yl)oxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) benzamide; 
 4-(2-(dimethylamino)-1-phenylethoxy)-3-methoxy-N-(5-(pyrimidin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-(benzyloxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-((methyl(pyridin-2-yl)amino)methyl)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-((1H-indol-1-yl)methyl)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) benzamide; 
 3-methoxy-4-(phenoxymethyl)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-((methyl(phenyl)amino)methyl)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 6-(2-hydroxy-2-methyl-1-phenylpropoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-((1-phenylpropan-2-yl)oxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-((1,3-dimethyl-1H-pyrazol-5-yl)methoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)-6-(thiophen-3-ylmethoxy)nicotinamide; 
 6-(3-(dimethylamino)-1-phenylpropoxy)-N-(5-(3-fluoropyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(1-phenylpropoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(1-(4-chlorophenyl)propoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(2,3-dihydro-1H-inden-1-yl)oxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 6-((6,7-dihydro-5H-cyclopenta[b]pyridin-5-yl)oxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(3-(dimethylamino)-1-phenylpropoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 6-(3-hydroxy-3-phenylpropoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(benzyloxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(methyl(1-phenylethyl)amino)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 6-((2-(dimethylamino)-2-phenylethyl)amino)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(2,3-dihydro-1H-inden-2-yl)amino)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 6-((1-(pyridin-2-yl)ethyl)amino)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 6-((1-(pyridin-3-yl)propan-2-yl)amino)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 6-((1-phenylethyl)amino)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 4-((6,7-dihydro-5H-cyclopenta[b]pyridin-5-yl)oxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-((2,3-dihydrobenzofuran-3-yl)oxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-(cyclopropyl(phenyl)methoxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) benzamide; 
 3-methoxy-4-(1-phenylethoxy)-N-(5-(pyrimidin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-((2,3-dihydro-1H-inden-2-yl)oxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-(1-phenylpropoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-phenethoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-((1-methyl-1H-pyrazol-3-yl)methoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-(pyridin-3-ylmethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) benzamide; 
 4-(benzyloxy)-3-chloro-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-(benzyloxy)-2-chloro-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-(pyridin-3-ylmethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-(1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-(benzyloxy)-2-fluoro-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-(benzyloxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-phenoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 6-phenoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-((1-(dimethylamino)-1-oxo-3-phenylpropan-2-yl)oxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-((4-phenylbutan-2-yl)oxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(2-phenylpropoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(3-(4-methoxyphenyl)propoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 5-methyl-6-(2-morpholino-1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 3-methoxy-4-(2-methoxy-1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) benzamide; 
 3-methoxy-4-(2-morpholino-1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-methoxy-4-(2-morpholino-1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 6-(3-(dimethylamino)-1-phenylpropoxy)-5-methoxy-N-(5-(pyrimidin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(2-(3,3-difluoropyrrolidin-1-yl)-1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(2-(4-methylpiperazin-1-yl)-1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 6-(1-phenyl-3-(pyrrolidin-1-yl)propoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 5-methoxy-6-(1-phenyl-2-(pyrrolidin-1-yl)ethoxy)-N-(5-(pyrimidin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-methoxy-6-(1-phenyl-2-(pyrrolidin-1-yl)ethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-methyl-6-(1-phenyl-2-(pyrrolidin-1-yl)ethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)nicotinamide; 
 5-methoxy-6-(1-phenylethoxy)-N-(5-(pyrimidin-4-yl)-1,3,4-thiadiazol-2-yl) nicotinamide; 
 4-(2-(dimethylamino)-1-phenylethoxy)-3-fluoro-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 3-chloro-4-(2-(dimethylamino)-1-phenylethoxy)-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; 
 4-(1-(4-fluorophenyl)-2-hydroxyethoxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide; and 
 4-(2-(dimethylamino)-1-(4-fluorophenyl)ethoxy)-3-methoxy-N-(5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl)benzamide. 
 
     
     
         12 . The method according to  claim 1 , whether the said at least one amido thiadiazole derivative is to be administered in combination with at least one co-agent useful in the treatment of cancer. 
     
     
         13 . The method according to  claim 1 , wherein the disorder is selected from a melanoma, a skin cancer, a breast cancer, a hemangioma or angiofibroma and the like cancer where there is neovascularization of a tumor of the skin, lung, pancreas, breast, colon, laryngeal, ovarian, prostate, colorectal, head, neck, testicular, lymphoid, marrow, bone, sarcoma, renal, sweat gland tissues and glioblastoma. 
     
     
         14 . The method according to  claim 1 , wherein the disorder is angiogenesis or an angiogenesis-dependent condition. 
     
     
         15 . The method according to  claim 1 , wherein the disorder is an inflammatory disorder. 
     
     
         16 . The method according to  claim 1 , wherein the disorder is pain, in particular inflammatory pain. 
     
     
         17 . The method according to  claim 1 , wherein said amido thiadiazole derivative is to be administered in combination with radiation therapy. 
     
     
         18 . The method according to  claim 15 , wherein the inflamed tissue is an arthritic tissue or psoriatic tissue. 
     
     
         19 . The method according to  claim 1 , wherein the disease or disorder affecting the eye and/or the lens is selected from cataract including diabetic cataract, re-opacification of the lens post cataract surgery, diabetic and other forms of retinopathies like Glaucoma, Aged-related Macular degeneration (AMD), Dry eye syndrome and allergic conjunctivitis. 
     
     
         20 . The method according to  claim 1 , wherein the skin disease or disorder is selected from psoriasis, eczema, scleroderma, xeroderma pigmentosum, skin cancers, melanoma, erythropoietic protoporphyria, discoid lupus erythematosus, solar urticaria, polymorphous light eruption, dermatitis, wound healing and scar formation.