Substituted thiophenes and uses thereof

Abstract

This invention relates to novel compounds having the structural formula (I) and to their pharmaceutical salts, compositions and methods of use. These novel compounds provide a treatment or prophylaxis of cancer.

1 . A compound of formula (I) or a pharmaceutically acceptable salt or in vivo-hydrolysable precursors thereof: 
     
       
         
         
             
             
         
       
     
     wherein:
 R 1  and R 2  are at each occurrence independently selected from H, optionally substituted C 1-6 alkyl, or optionally substituted heterocyclyl; with the proviso that R 1  and R 2  are not both H; 
 
     or R 1  and R 2  and the N to which they are attached in combination form an optionally substituted heterocyclyl;
 R 4  is selected from H, OH, optionally substituted carbocyclyl, optionally substituted heterocyclyl, or optionally substituted C 1-6 alkyl; 
 R 5  is selected from H, optionally substituted carbocyclyl, or optionally substituted C 1-6 alkyl. 
 
   
   
       2 . A compound of formula (I) or a pharmaceutically salt or an in vivo-hydrolysable precursor thereof as recited in  claim 1  wherein R 2 , R 4 , and R 5  have any of the meanings defined in  claim 1  and
 R 1  is an optionally substituted heterocyclyl.   
   
   
       3 . A compound of formula (I) or a pharmaceutically salt or an in vivo-hydrolysable precursor thereof as recited in  claim 1  wherein R 2 , R 4 , and R 1  have any of the meanings defined in  claim 1  and R 1  is an optionally substituted heterocyclyl wherein 1,2, or 3 substitutents is/are independently selected from halogen, nitro, amino, cyano, trifluoromethyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, hydroxy, alkylhydroxy, carbonyl, —CH(OH)CH 3 , —CH 2 NH-alkyl-OH, alkyl-(OH)CH 3 , —CH 2 -phenyl-(OCH 3 ) 2 , —Oalkyl, —OCH 3 , —Ophenyl, —OCOalkyl, —NHCHO, —Nalkyl, —N-(alkyl)-CHO, —NH—CO-amino, —N-(alkyl)-CO-amino, —NH—COalkyl, —N-(alkyl)-COalkyl, -carboxy, -amidino, —CO-amino, —CO-alkyl, —CO 2 alkyl, mercapto, —Salkyl, —SCH 2 furanyl, —SO(alkyl), —SO 2 (alkyl), —SO 2 -amino, -alkylsulfonylamino, phenyl, anisole, dimethoxyphenyl, trimethoxyphenyl, halophenyl, cycloalkyl, heterocyclyl, -alkyl-NH-cycloalkyl, -alkyl-NH— heterocyclyl, -alkyl-NH-alkyl-OH, —C(═O)OC(CH 3 ) 3 , —N(CH 3 ) 2 , —N(CH 2 CH 3 ) 2 , -alkyl-NH-alkyl-heterocyclyl, -alkyl-aryl, -methyl-phenyl, alkyl-polycyclyl, alkyl-amino, alkyl-hydroxy, —CH 2 NH-alkyl-heterocyclyl, —CH 2 NHCH 2 CH(CH 3 ) 2 , vicinal —O(alkyl)O—, vicinal —OC(haloalkyl)O—, vicinal —CH 2 O(alkyl)O—, vicinal —S(alkyl)S— and —O(alkyl)S—. 
   
   
       4 . A compound of formula (I) or a pharmaceutically salt or an in vivo-hydrolysable precursor thereof as recited in  claim 1  wherein R 2 , R 4 , and R 5  have any of the meanings defined in  claim 1  and R 1  is an optionally substituted heterocyclyl wherein 1,2, or 3 substitutents is/are independently selected from: —OH, C(═O)OC(CH 3 ) 3 , NH 2 , C 1-6 alkyl, methoxybenzene, or dimethoxy benezene. 
   
   
       5 . A compound of formula (I) or a pharmaceutically salt or an in vivo-hydrolysable precursor thereof as recited in  claim 1  wherein R 2 , R 4 , and R 5  have any of the meanings defined in  claim 1  and
 R 1  is a heterocyclyl wherein heterocyclyl is selected from piperidinyl, pyridinyl, pyrrolidinyl, pyrazinyl, azepanyl, azetidinyl, azabicyclozinyl, furanyl, thienyl.   
   
   
       6 . A compound of formula (I) or a pharmaceutically salt or an in vivo-hydrolysable precursor thereof as recited in  claim 1  wherein R 1 , R 4 , and R 5  have any of the meanings defined in  claim 1  and
 R 2  is H.   
   
   
       7 . A compound of formula (I) or a pharmaceutically salt or an in vivo-hydrolysable precursor thereof as recited in  claim 1  wherein R 1 , R 2 , and R 5  have any of the meanings defined in  claim 1  and
 R 4  is H.   
   
   
       8 . A compound of formula (I) or a pharmaceutically salt or an in vivo-hydrolysable precursor thereof as recited in  claim 1  wherein R 1 , R 2 , and R 4  have any of the meanings defined in  claim 1  and
 R 5  is H or an optionally substituted C 1-6 alkyl.   
   
   
       9 . A compound of formula (I) or a pharmaceutically salt or an in vivo-hydrolysable precursor thereof as recited in  claim 1  wherein R 1 , R 2 , and R 4  have any of the meanings defined in  claim 1  and
 R 5  is H or an optionally substituted C 1-6 alkyl wherein 1, 2 or 3 substitutents is/are independently selected from: NH 2 , NHCH 3 , N(CH 2 CH 3 ) 2 , N(CH 3 ) 2 , OCH 3 , OH, —C 1-6 alkyl, morpholino, piperidinyl, pyrrolodinyl.   
   
   
       10 . A compound of formula (I) or a pharmaceutically salt or an in vivo-hydrolysable precursor thereof as recited in  claim 1  wherein R 1 , R 2 , and R 4  have any of the meanings defined in  claim 1  and
 R 5  is H or an optionally substituted C 1-3 alkyl.   
   
   
       11 . A compound of formula (I) or a pharmaceutically salt or an in vivo-hydrolysable precursor thereof as recited in  claim 1  wherein R 1 , R 2 , and R 4  have any of the meanings defined in  claim 1  and
 R 5  is H or an optionally substituted C 1-3 alkyl wherein 1, 2 or 3 substitutents is/are   independently selected from: NH 2 , NHCH 3 , N(CH 2 CH 3 ) 2 , N(CH 3 ) 2 , OCH 3 , OH, —C 1-6 alkyl, morpholino, piperidinyl, pyrrolodinyl.   
   
   
       12 . A compound of formula (I) or a pharmaceutically salt or an in vivo-hydrolysable precursor thereof, as recited in  claim 1  wherein:
 R 1  is an optionally substituted heterocyclyl;   R 2  is H;   R 4  is H;   R 5  is H or an optionally substituted C 1-6 alkyl.   
   
   
       13 . A compound of formula (I) or a pharmaceutically salt or an in vivo-hydrolysable precursor thereof, as recited in  claim 1  wherein:
 R 1  is an optionally substituted heterocyclyl wherein the substitutent is selected from one or more of the following: —NH 2 , C 1-6 alkyl, —C(═O)OC(CH 3 ) 3 ,   R 2  is H;   R 4  is H;   R 5  is H or an optionally substituted C 1-6 alkyl wherein the substitutent is selected from one or more of the following: —C 1-6 alkyl, —N(C 1-3 alkyl) 2 .   
   
   
       14 . A compound of formula (I) or a pharmaceutically salt or an in vivo-hydrolysable precursor thereof, as recited in  claim 1  wherein:
 R 1  is an optionally substituted heterocyclyl wherein the substitutent is selected from one or more of the following: —NH 2 , C 1-6 alkyl, —C(═O)OC(CH 3 ) 3 ,   R 2  is H;   R 4  is H;   R 5  is H or an optionally substituted C 1-3 alkyl wherein 1, 2 or 3 substitutents is/are independently selected from: NH 2 , NHCH 3 , N(CH 2 CH 3 ) 2 , N(CH 3 ) 2 , OCH 3 , OH, —C 1-6 alkyl, morpholino, piperidinyl, pyrrolodinyl.   
   
   
       15 . A compound of formula (I) or a pharmaceutically salt or an in vivo-hydrolysable precursor thereof, as recited in  claim 1  wherein:
 R 1  is a heterocyclyl;   R 2  is H;   R 4  is H;   R 5  is H or a C 1-6 alkyl.   
   
   
       16 . A compound of formula (I) or a pharmaceutically salt or an in vivo-hydrolysable precursor thereof, as recited in  claim 1  wherein:
 R 1  is a 6-membered heterocyclyl containing at least one N in the ring;   R 2  is H;   R 4  is H;   R 5  is a C 1-3 alkyl.   
   
   
       17 . A compound of formula (I) selected from: 
     tert-butyl 3-{[(2-[(aminocarbonyl)amino]-5-{4-[2-(diethylamino)ethoxy]phenyl}-3-thienyl)carbonyl]amino}piperidine-1-carboxylate; 
     2-[(aminocarbonyl)amino]-5-{4-[2-(diethylamino)ethoxy]phenyl}-N-piperidin-3-ylthiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-{3-[2-(diethylamino)ethoxy]phenyl}-N-piperidin-3-ylthiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide; 
     tert-butyl 3-{[(2-[(aminocarbonyl)amino]-5-{3-[2-(diethylamino)ethoxy]phenyl}-3-thienyl)carbonyl]amino}piperidine-1-carboxylate; 
     2-[(aminocarbonyl)amino]-5-{4-[2-(diethylamino)ethoxy]phenyl}-N-piperidin-4-ylthiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-N-[(3R)-azepan-3-yl]-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     N-(3-[(4-aminopiperidin-1-yl)carbonyl]-5-{4-[2-(diethylamino)ethoxy]phenyl}-2-thienyl)urea; 
     2-[(aminocarbonyl)amino]-5-{4-[2-(diethylamino)ethoxy]phenyl}-N-[3-(hydroxymethyl)phenyl]thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-{3-[2-(diethylamino)ethoxy]phenyl}-N-piperidin-4-ylthiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-N-(2-aminoethyl)-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-piperidin-4-ylthiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-{3-[2-(diethylamino)ethoxy]phenyl}-N-pyridin-3-ylthiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(1-methylpiperidin-4-yl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-[(3S)-1-methylazepan-3-yl]thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-{3-[2-(diethylamino)ethoxy]phenyl}-N-[3-(hydroxymethyl)phenyl]thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-{4-[2-(diethylamino)ethoxy]phenyl}-N-pyrrolidin-3-ylthiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-{4-[2-(diethylamino)ethoxy]phenyl}-N-pyridin-3-ylthiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-[(3S)-1-methylpiperidin-3-yl]thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-{3-[2-(diethylamino)ethoxy]phenyl}-N-pyrrolidin-3-ylthiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-[(3R)-piperidin-3-ylmethyl]thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-[(3S)-pyrrolidin-3-yl]thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-[(3R)-pyrrolidin-3-yl]thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-N-[2-(dimethylamino)ethyl]-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-N-[2-(diethylamino)ethyl]-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-N-[(3S)-azepan-3-yl]-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-[(3R)-piperidin-3-yl]thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(piperidin-4-ylmethyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-pyrrolidin-3-ylthiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-N-(1-ethylpiperidin-3-yl)-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-N-[(3S)-1-ethylazepan-3-yl]-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(3-hydroxyphenyl)-N-piperidin-4-ylthiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-hydroxyphenyl)-N-piperidin-4-ylthiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(3-methoxyphenyl)-N-piperidin-4-ylthiophene-3-carboxamide; 
     tert-butyl (3S)-3-({[2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-3-thienyl]carbonyl}amino)pyrrolidine-1-carboxylate; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-piperidin-3-ylthiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-N-(1-benzylpiperidin-4-yl)-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     tert-butyl 3-({[2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-3-thienyl]carbonyl}amino)piperidine-1-carboxylate; 
     2-[(aminocarbonyl)amino]-5-[4-(2-piperidin-1-ylethoxy)phenyl]-N-(2-pyridin-4-ylethyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-[4-(2-piperidin-1-ylethoxy)phenyl]-N-(2-pyridin-4-ylethyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl amino]-N-azetidin-3-yl-5-(4-methoxyphenyl)thiophene-3-carboxamide, 2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-[(2S)-pyrrolidin-2-ylmethyl]thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-pyridin-4-ylthiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(2-piperazin-1-ylethyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(2-piperidin-1-ylethyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-N-1-azabicyclo[2.2.2]oct-3-yl-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-N-(2-hydroxyethyl)-5-(4-hydroxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-N-(trans-4-hydroxycyclohexyl)-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-hydroxyphenyl)-N-(2-pyridin-4-ylethyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(2-piperazin-1-ylethyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(2-pyridin-4-ylethyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-hydroxyphenyl)-N-(2-pyridin-3-ylethyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(2-pyridin-3-ylethyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(2-methoxyphenyl)-N-piperidin-4-ylthiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(tetrahydrofuran-2-ylmethyl)thiophene-3-carboxamide; 
     tert-butyl (3R)-3-({[2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-3-thienyl]carbonyl}amino)piperidine-1-carboxylate; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(pyridin-3-ylmethyl)thiophene-3-carboxamide; 
     tert-butyl 3-({[2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-3-thienyl]carbonyl}amino)azetidine-1-carboxylate; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(pyridin-4-ylmethyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(3-methoxypropyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-[2-(2-thienyl)ethyl]thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(2-thienylmethyl)thiophene-3-carboxamide; 
     N-[3-(1,4-diazepan-1-ylcarbonyl)-5-(4-methoxyphenyl)-2-thienyl]urea; 
     2-[(aminocarbonyl)amino]-N-(2-methoxyethyl)-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-hydroxyphenyl)-N-(2-thienylmethyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-N-{2-[(2-furylmethyl)thio]ethyl}-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-hydroxyphenyl)-N-[2-(2-thienyl)ethyl]thiophene-3-carboxamide; 
     N-(3-[(4-aminopiperidin-1-yl)carbonyl]-5-{3-[2-(diethylamino)ethoxy]phenyl}-2-thienyl)urea; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-[(3R)-piperidin-3-ylmethyl]thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(1,2,3,4-tetrahydroquinolin-3-yl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-N-(1,3-benzodioxol-5-ylmethyl)-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-N-(3-methoxybenzyl)-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-N-[2-(3,4-dimethoxyphenyl)ethyl]-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-[(5-methyl-2-furyl)methyl]thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(pyridin-2-ylmethyl)thiophene-3-carboxamide; 2-[(aminocarbonyl)amino]-N-(4-fluorobenzyl)-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     tert-butyl 4-({[2-[(aminocarbonyl)amino]-5-(3-methoxyphenyl)-3-thienyl]carbonyl}amino)piperidine-1-carboxylate; 
     2-[(aminocarbonyl)amino]-N-(2-methoxybenzyl)-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(2-phenoxyethyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-N-(2-pyridin-2-ylethyl)thiophene-3-carboxamide; 
     tert-butyl 4-({[2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-3-thienyl]carbonyl}amino)piperidine-1-carboxylate; 
     2-[(aminocarbonyl)amino]-N-(4-methoxybenzyl)-5-(4-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-{4-[2-(diethylamino)ethoxy]phenyl}-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-{4-[2-(diethylamino)ethoxy]phenyl}-N-[(3R)-piperidin-3-yl]thiophene-3-carboxamide; 
     tert-butyl (3S)-3-{[(2-[(aminocarbonyl)amino]-5-{4-[2-(diethylamino)ethoxy]phenyl}-3-thienyl)carbonyl]amino}piperidine-1-carboxylate; 
     2-[(aminocarbonyl)amino]-N-[(3S)-azepan-3-yl]-5-{4-[2-(diethylamino)ethoxy]phenyl}thiophene-3-carboxamide; 
     tert-butyl (3R)-3-{[(2-[(aminocarbonyl)amino]-5-{4-[2-(diethylamino)ethoxy]phenyl}-3-thienyl)carbonyl]amino}piperidine-1-carboxylate; 
     N-[3-{[(3S)-3-aminoazepan-1-yl]carbonyl}-5-(4-methoxyphenyl)-2-thienyl]urea; 
     5-{4-[2-(diethylamino)ethoxy]phenyl}-2-{[(pyrazin-2-ylamino)carbonyl]amino}-N-[(3S)-pyrrolidin-3-yl]thiophene-3-carboxamide; 
     5-{3-[2-(diethylamino)ethoxy]phenyl}-2-{[(pyrazin-2-ylamino)carbonyl]amino}-N-[(3S)-pyrrolidin-3-yl]thiophene-3-carboxamide; 
     5-{3-[2-(diethylamino)ethoxy]phenyl}-N-piperidin-4-yl-2-{[(pyrazin-2-ylamino)carbonyl]amino}thiophene-3-carboxamide; 
     N-[(3S)-azepan-3-yl]-5-(4-methoxyphenyl)-2-{[(pyrazin-2-ylamino)carbonyl]amino}thiophene-3-carboxamide;. 
     5-{3-[2-(diethylamino)ethoxy]phenyl}-N-piperidin-3-yl-2-{[(pyrazin-2-ylamino)carbonyl]amino}thiophene-3-carboxamide; 
     N-(2-aminoethyl)-5-(4-methoxyphenyl)-2-{[(pyrazin-2-ylamino)carbonyl]amino}thiophene-3-carboxamide; 
     5-{4-[2-(diethylamino)ethoxy]phenyl}-N-piperidin-3-yl-2-{[(pyrazin-2-ylamino)carbonyl]amino}thiophene-3-carboxamide; 
     5-(4-methoxyphenyl)-N-piperidin-4-yl-2-{[(pyrazin-2-ylamino)carbonyl]amino}thiophene-3-carboxamide; 
     tert-butyl 3-{[(5-{3-[2-(diethylamino)ethoxy]phenyl}-2-{[(pyrazin-2-ylamino)carbonyl]amino}-3-thienyl)carbonyl]amino}piperidine-1-carboxylate; 
     5-{4-[2-(diethylamino)ethoxy]phenyl}-N-piperidin-4-yl-2-{[(pyrazin-2-ylamino)carbonyl]amino}thiophene-3-carboxamide; 
     5-(4-methoxyphenyl)-2-{[(pyrazin-2-ylamino)carbonyl]amino}-N-[(3S)-pyrrolidin-3-yl]thiophene-3-carboxamide; 
     N-[3-(1,4-diazepan-1-ylcarbonyl)-5-(4-methoxyphenyl)-2-thienyl]-N′-pyrazin-2-ylurea; 
     N-[3-[(3-aminopyrrolidine-1-yl)carbonyl]-5-(4-methoxyphenyl)-2-thienyl]-N′-pyrazin-2-ylurea; 
     tert-butyl 4-{[(5-(4-methoxyphenyl)-2-{[(pyrazin-2-ylamino)carbonyl]amino}-3-thienyl)carbonyl]amino}piperidine-1-carboxylate; 
     tert-butyl 3-{[(5-{4-[2-(diethylamino)ethoxy]phenyl}-2-{[(pyrazin-2-ylamino)carbonyl]amino}-3-thienyl)carbonyl]amino}piperidine-1-carboxylate; 
     5-[4-(2-diethylamino-ethoxy)-phenyl]-2-(3-hydroxy-urea)-thiophene-3-carboxylic acid-(S)-piperidin-3-ylamide; 
     2-[(aminocarbonyl)amino]-N-[(3S)-azepan-3-yl]-5-(3-methoxyphenyl)thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(2-hydroxyphenyl)-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-(3-methoxyphenyl)-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide; 
     2-[(aminocarbonyl)amino]-5-[2-(benzyloxy)phenyl]-N-[(3S)-piperidin-3-yl]thiophene-3-carboxamide. 
   
   
       18 . A compound of formula (I) or a pharmaceutically acceptable salt thereof as recited in any one of  claims 1  to  17  for use as a medicament. 
   
   
       19 . The use of a compound of formula (I) or a pharmaceutically acceptable salt thereof as recited in any one of  claims 1  to  17 , in the manufacture of a medicament for the treatment or prophylaxis of disorders associated with cancer. 
   
   
       20 . A method for the treatment of cancer comprising administering to a human a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof as defined in any one of  claims 1  to  17 . 
   
   
       21 . A method for the treatment of breast cancer, colorectal cancer, ovarian cancer, lung (non small cell) cancer, malignant brain tumors, sarcomas, melanoma and lymphoma by administering a compound of formula I or a pharmaceutically acceptable salt thereof as defined in any one of  claims 1  to  17 . 
   
   
       22 . A method of treating cancer by administering to a human a compound of formula (I) or a pharmaceutically acceptable salt thereof as defined in any one of  claims 1  to  17  and an anti-tumor agent. 
   
   
       23 . A method of treating cancer by administering to a human a compound of formula (I) or a pharmaceutically acceptable salt thereof as defined in any one of  claims 1  to  17  and a DNA damaging agent. 
   
   
       24 . A method for the treatment of infections associated with cancer comprising administering to a host in need of such treatment a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof as defined in any one of  claims 1  to  17 . 
   
   
       25 . A method for the prophylaxis treatment of infections associated with cancer comprising administering to a host in need of such treatment a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof as defined in any one of  claims 1  to  17 . 
   
   
       26 . A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof as defined in any one of  claims 1  to  17  together with at least one pharmaceutically acceptable carrier, diluent or excipient. 
   
   
       27 . A process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt or in vivo-hydrolysable precursors thereof as defined in any one of  claims 1  to  17 , which comprises:
 (a) the reaction of a 2-aminothiophene shown below as Formula I   
     
       
         
         
             
             
         
       
     
     wherein the hydrogen at the 2-amino position is displaced to form an amide, shown as formula III below 
     
       
         
         
             
             
         
       
     
     wherein the methyl ester is converted to an amide utilizing the desired amine in conjunction with an aluminate organometallic complex, to give the product shown as formula IV below: 
     
       
         
         
             
             
         
       
     
     Wherein the amide is converted to various substituted secondary ureas by the reaction with various isocyanantes to yield the product shown as formula V below: 
     
       
         
         
             
             
         
       
     
   
   
       28 . The use of a compound of formula (VI) below or a pharmaceutically acceptable salt or an in vivo hydrolysable precursor in the manufacture of a compound of formula (I) as set forth in any one of  claims 1 - 17 .