Compounds and methods of treating cell proliferative diseases

Abstract

The present invention relates to compounds and their uses, particularly in the pharmaceutical industry. The invention discloses compounds having anti-proliferative activities, as well as methods for treating various diseases associated with abnormal cell proliferation, including cancer, by administering said compounds. It further deals with pharmaceutical compositions comprising said compounds, more particularly useful to treat cancers.

1 - 21 . canceled  
     
     
         22 . A compound having a general formula (I):  
       
         
           
           
               
               
           
         
       
       wherein: 
 R 1  is CH 2 R 3  or COR 3 ;  
 R 2  represents a hydrogen atom or an alkenyl group containing from 3 to 6 carbon atoms;  
 R 3  is —OH, —OR 4 , —SR 4 , —NR 5 R 6 , or  
                     
 R 4  represents a group selected from alkyl containing from 1 to 6 carbon atoms, a cycloalkyl group a radical —CONR 5 R 6 , aryl, a 5- to 12-membered heterocyclic ring which has 1 to 3 hetero-atoms selected from oxygen, sulfur and nitrogen, heteroaryl, aralkyl, heteroaralkyl, alkanoyl or cycloalkanoyl from 2 to 6 carbon atoms, arylcarbonyl, heteroarylcarbonyl, arylalkanoyl and heteroarylalkanoyl;  
 R 5  and R 6 , independently from each other, are selected from a hydrogen atom, an alkyl group having from 1 to 10 carbon atoms, an aryl and an aralkyl;  
 m is 2 or 3;  
 “linker” represents (CH 2 ) n , wherein n represents an integer between 1 and 10 inclusive or a xylenyl group;  
 Y represents an oxygen atom, a sulfur atom or a radical —NR 7 —;  
 R 7 , identical or different, is selected from a group consisting of a hydrogen atom, an alkyl group having from 1 to 10 carbon atoms, an aryl and an aralkyl; 
 either:  
 
 X represents an oxygen atom, a sulfur atom or a radical —NR 7 —;  
 A represents either a substituted phenyl group of formula  
                     
  in which:  
 R 8 , R 9 , R 10  and R 11 , independently from each other, are selected from a hydrogen atom, a halogen atom (preferably F, Cl, or Br), a hydroxyl group, a (C 1 -C 10 )alkyl group, an alkenyl group, an (C 1 -C 10 )alkanoyl group, a (C 1 -C 10 )alkoxy group, a (C 1 -C 10 )alkoxycarbonyl group, an aryl group, an aralkyl group, an arylcarbonyl group, a mono- or poly-cyclic hydrocarbon group, a —NHCO(C 1 -C 6 )alkyl group, —NO 2 , —CN, a —NR 12 R 13  group or a trifluoro(C 1 -C 6 )alkyl group; preferably R 8 , R 9 , R 10  and R 11 , not being simultaneously hydrogen atom,  
 or alternatively two substituents, R 8  and R 9 , may form together a mono- or poly-cyclic hydrocarbon group with the carbon atoms of the phenyl group they are attached and the two other substituents, R 10  and R 11 , are as defined above;  
 or A represents a 5- to 12-membered heterocyclic ring which has 1 to 3 hetero-atoms selected from oxygen, sulfur and nitrogen, said ring is bonded directly to X;  
 R 12  and R 13 , independently from each other, are selected in the group consisting of a hydrogen atom, an alkyl group having from 1 to 10 carbon atoms, an aryl and an aralkyl; 
 or X-A represents a group of formula (II):  
                     
  wherein:  
 
 R 14 , R 15 , R 16 , R 17 , R 18  and R 19 , independently from each other, represent a hydrogen atom, a halogen atom (preferably F, Cl, or Br), a hydroxyl group, a (C 1 -C 10 )alkyl group, an (C 1 -C 10 )alkanoyl group, a (C 1 -C 10 )alkoxy group, an aryl group, an aralkyl group, an arylcarbonyl group, a mono- or poly-cyclic hydrocarbon group, —NO 2 , —CN, a —NR 12 R 13  group or a trifluoro(C 1 -C 6 )alkyl group, R 12  and R 13  being as defined above; alternatively, R 14  and R 15  may form together with the bond they are attached thereto a cycloalkyl group (preferably a cyclohexyl group) or an aryl group (preferably a phenyl group);  
 W represents a carbon or nitrogen atom;  
 Z represents a carbon or nitrogen atom;  
 With the provisos that: 
 when X and Y are oxygen atoms, A is a phenyl group, R 2  is a hydrogen atom, linker is (CH 2 ) n , wherein n is 5 and R 8  on the ortho position on the phenyl group vis-à-vis X is n-propyl group, then at least one R 9 , R 10  and R 11  is different from hydrogen;  
 when X and Y are oxygen atoms, A is a phenyl group, R 2  is a hydrogen atom, linker is (CH 2 ) n , wherein n is 3 or 5, R 8  on the ortho position on the phenyl group vis-à-vis X is n-propyl group, R 9  on the meta position vis-à-vis X is an hydroxyl group, and R 10  on the para position vis-à-vis X is an acetyl group; then R 11  is different from hydrogen;  
 when X and Y are oxygen atoms, R 2  is a hydrogen atom, linker is (CH 2 ) n , wherein n is 2 or 3, then A is different from a non-substituted naphthalene group;  
 its tautomers, optical and geometrical isomers, racemates, salts, hydrates and mixtures thereof.  
 
 
     
     
         23 . A compound according to  claim 22 , wherein: 
 X is oxygen or sulfur; and/or    Y is oxygen; and/or    linker is (CH 2 ) n , wherein, n is from 4 to 7 inclusive or a xylenyl group (meta, para, or ortho); and/or    R 1  is —CH 2 OH, —CH 2 —O-benzyl, —CH 2 —O-tetrahydropyran, —CO 2 H or —CO—NH-benzyl; and/or    R 2  is a hydrogen atom, a propen-1-yl group, a propen-2-yl group; and/or    A is a substituted phenyl, a pyridine group (preferably pyridin-2-yl group), a furan or a thiophene group, optionally substituted.    
     
     
         24 . A compound according to  claim 22 , wherein A is a phenyl substituted by at least one halogen atom, preferably chlorine.  
     
     
         25 . A compound according to  claim 22 , wherein A is a phenyl group substituted with at least two substituents simultaneously represent Cl.  
     
     
         26 . A compound according to  claim 22 , wherein A is a substituted, at least one of the substituents on the phenyl group is a halogen atom, an alkyl group (preferably propyl) or an alkenyl (preferably propenyl), a trifluoroalkyl group (trifluoromethyl group), —NO 2 , —CN, an alkoxy group (preferably methoxy or butoxy, optionnally substituted with a cycloalkyl group (preferably cyclopropyl), an alkoxycarbonyl group (preferably —COOC 2 H 5 ), a alkanoyl group (preferably acetyl), a —NR 12 R 13  group, preferably wherein R 12  is H and R 13  is hydrogen or an alkyl group (more preferably ethyl group), or a —NHCO(C 1 -C 6 )alkyl group (preferably —NHCOCH 3 ).  
     
     
         27 . A compound according to  claim 22 , wherein A is a substituted phenyl, R 8  represents a hydrogen atom, a propyl group or an ethoxy group, R 9  and R 10  represent a hydrogen atom, or an halogen atom, preferably chlorine, and R 11  is a hydrogen atom.  
     
     
         28 . A compound according to  claim 22 , wherein A is a substituted pyridine (preferably pyridin-2-yl), the pyridin is substitued with at least a halogen atom, preferably chlorine, and/or trifluoroalkyl (preferably trifluoromethyl).  
     
     
         29 . A compound according to  claim 22 , wherein A is a substituted thiophene, the thiophene is substitued with at least a halogen atom, preferably bromine, and/or an alkoxycarbonyl group (preferably —COOCH 3 ).  
     
     
         30 . A compound according to  claim 22 , wherein A is a substituted furan, the furan is substitued with at least one, or more specifically two, alkyl group (preferably CH 3 ).  
     
     
         31 . A compound according to  claim 22 , wherein X-A represents a group of formula (II), and wherein: 
 W and z represent a carbon atom and a double bond is present between the carbon atoms of the cycle supporting R 14  and R 15 , or    W represents a nitrogen atom, z represents a carbon atom and a double bond is present between the carbon atoms of the cycle supporting R 14  and R 15 , or    W and z represent a carbon atom and a single bond is present between the carbon atoms of the cycle supporting R 14  and R 15 , or    W and z represent a nitrogen atom atom and a double bond is present between the carbon atoms of the cycle supporting R 14  and R 15 .    
     
     
         32 . A compound according to  claim 22 , wherein X-A represents a group of formula (II) and wherein W and z represent a carbon atom and a double bond is present between the carbon atoms of the cycle supporting R 14  and R 15 .  
     
     
         33 . A compound according to  claim 22 , wherein X-A represents a group of formula (II) and wherein: 
 Y is oxygen; and/or    linker is (CH 2 ) n , wherein, n is from 2 to 8 inclusive, preferably 5, or a xylenyl group; and/or    R 1  is —CH 2 OH, —CH 2 OCONR 5 R 6 , wherein R 5  is preferably H and R6 is preferably ethyl, cyclohexyl, phenyl, optionally substituted with halogen atom (preferably Cl) or with NO 2 , —CH 2 OCO-alkyl (preferably propyl), —CH 2 OCO-cycloalkyl (wherein preferably cycloalkyl is cyclohexyl), —CH 2 —O—CO-benzyl, —CH 2 —O—CO-aryl (wherein aryl is preferably phenyl or furan), —CH 2 —O-tetrahydropyran, —CO 2 H or —CO—NH-benzyl; and/or    R 2  is a hydrogen atom, a propen-1-yl group, a propen-2-yl group.    
     
     
         34 . A compound according to  claim 22 , wherein X-A is the group of formula (II) and R 14 , R 15 , R 16 , R 17 , R 18  and R 19 , independently from each other, represent a hydrogen atom, a aryl group (preferably a phenyl group), an alkyl group (preferably a methyl group), an alkoxy group (preferably a methoxy group), a halogen atom (preferably Cl or F).  
     
     
         35 . A compound according to  claim 22 , wherein X-A is the group of formula (II), R 14  and R 15  form together with the bond they are attached thereto a cycloalkyl group (preferably a cyclohexyl group) or an aryl group (preferably a phenyl group) and R 16 , R 17 , R 18  and R 19 , independently, represent preferably a hydrogen atom and/or an alkyl group.  
     
     
         36 . A compound according to  claim 22 , wherein X-A is the group of formula (II), R 14 , R 15 , R 16 , R 17 , R 18  and R 19  represent a hydrogen atom.  
     
     
         37 . A compound according to  claim 22 , which is chosen in the group consisting of: 
 5-[5-(4-Chlorophenyloxy)pentyloxy]-2-(hydroxymethyl)-4H-pyran-4-one    5-[5-(3-Chlorophenyloxy)pentyloxy]-2-(hydroxymethyl)-4H-pyran-4-one    5-[5-(3,4-Dichlorophenyloxy)pentyloxy]-2-(hydroxymethyl)-4H-pyran-4-one    5-[4-(3,4-Dichlorophenyloxy)butyloxy]-2-(hydroxymethyl)-4H-pyran-4-one    5-[5-(3,4-Dichloro-2-propylphenyloxy)pentyloxy]-2-(hydroxymethyl)-4H-pyran-4-one    5-[5-(4,5-Dichloro-2-propylphenyloxy)pentyloxy]-2-(hydroxymethyl)-4H-pyran-4-one    5-[5-(2-Ethyloxyphenyloxy)pentyloxy]-2-(hydroxymethyl)-4H-pyran-4-one    5-[6-(3,4-Dichloro-2-propylphenyloxy)hexyloxy]-2-(hydroxymethyl)-4H-pyran-4-one    5-[7-(3,4-Dichloro-2-propylphenyloxy) heptyloxy]-2-(hydroxymethyl)-4H-pyran-4-one    5-[9-(3,4-Dichlorophenyloxy)nonyloxy]-2-(hydroxymethyl)-4H-pyran-4-one    2-(Benzyloxymethyl)-5-[5-(3,4-dichlorophenyloxy)pentyloxy]-2-(hydroxymethyl)-4H-pyran-4-one    5-[5-(4-Chlorophenyloxy)pentyloxy]-4-oxo-4H-pyran-2-carboxylic acid    5-[5-(3-Chlorophenyloxy)pentyloxy]-4-oxo-4H-pyran-2-carboxylic acid    5-[5-(3,4-Dichlorophenyloxy)pentyloxy]-4-oxo-4H-pyran-2-carboxylic acid    5-[4-(3,4-Dichlorophenyloxy)butyloxy]-4-oxo-4H-pyran-2-carboxylic acid    5-[5-(3,4-Dichloro-2-propylphenyloxy)pentyloxy]-4-oxo-4H-pyran-2-carboxylic acid    5-[5-(2-Ethyloxyphenyloxy)pentyloxy]-4-oxo-4H-pyran-2-carboxylic acid    N-Benzyl-5-[5-(4-chlorophenyloxy)pentyloxy]-4-oxo-4H-pyran-2-carboxamide    (E)-3-[5-(4-Chlorophenyloxy)pentyloxy]-6-(hydroxymethyl)-2-(propen-1-yl)-4H-pyran-4-one    (E)-3-[5-(3-Chlorophenyloxy)pentyloxy]-6-(hydroxymethyl)-2-(propen-1-yl)-4H-pyran-4-one    (E)-3-[5-(3,4-Chlorophenyloxy)pentyloxy]-6-(hydroxymethyl)-2-(propen-1-yl)-4H-pyran-4-one    (E)-3-[5-(3,4-Chloro-2-propylphenyloxy)pentyloxy]-6-(hydroxymethyl)-2-(propen-1-yl)-4H-pyran-4-one    (E)-6-(Hydroxymethyl)-2-(propen-1-yl)-3-[5-(2-propylphenyloxy)pentyloxy]-4H-pyran-4-one    (E)-3-[5-(4-Chlorophenyloxy)pentyloxy]-2-(propen-1-yl)-4-oxo-4H-pyran-6-carboxylic acid    (E)-3-[5-(3-Chlorophenyloxy) pentyloxy]-2-(propen-1-yl)-4-oxo-4H-pyran-6-carboxylic acid    (E)-3-[5-(3,4-Dichlorophenyloxy)pentyloxy]-2-(propen-1-yl)-4-oxo-4H-pyran-6-carboxylic acid    (E)-3-[5-(3,4-Dichloro-2-propylphenyloxy)pentyloxy]-2-(propen-1-yl)-4-oxo-4H-pyran-6-carboxylic acid    (E)-2-(Propen-1-yl)-3-[5-(2-propylphenyloxy)pentyloxy]-4-oxo-4H-pyran-6-carboxylic acid    2-Fluoro-4-[5-(6-hydroxymethyl-4-oxo-4H-pyran-3-yloxy)-pentyloxy]-benzonitrile (EHT 2904)    5-[5-(2-Ally-4-chloro-phenoxy)-pentyloxy]-2-hydroxymethyl-4H-pyran-4-one (EHT 5431)    5-[5-(4-Chloro-2-propyl-phenoxy)-pentyloxy]-2-hydroxymethyl-4H-pyran-4-one (EHT 6152)    5-[5-(2-Allyl-3,5-dichloro-phenoxy)-pentyloxy]-2-hydroxymethyl-4H-pyran-4-one (EHT 6978)    5-[5-(3,5-Dichloro-2-propyl-phenoxy)-pentyloxy]-2-hydroxymethyl-4H-pyran-4-one (EHT2991)    (E)-3-[5-(3,5-Bis-trifluoromethyl-phenoxy)-pentyloxy]-6-hydroxymethyl-2-propenyl-4H-pyran-4-one (EHT 5403)    (E)-3-[5-(3,4-Difluoro-phenoxy)-pentyloxy]-6-hydroxymethyl-2-propenyl-4H-pyran-4-one (EHT 8307)    (E)-2-Fluoro-4-[5-(6-hydroxymethyl-4-oxo-2-propenyl-4H-pyran-3-yloxy)-pentyloxy]-benzonitrile (EHT 4112)    (E)-3-[5-(2-Allyl-4-chloro-phenoxy)-pentyloxy]-6-hydroxymethyl-2-propenyl-4H-pyran-4-one (EHT 9226)    (E)-3-[5-(4-Chloro-2-propyl-phenoxy)-pentyloxy]-6-hydroxymethyl-2-propenyl-4H-pyran-4-one (EHT 1405)    (E)-3-[5-(2-Allyl-3,5-dichloro-phenoxy)-pentyloxy]-6-hydroxymethyl-2-propenyl-4H-pyran-4-one (EHT 6506)    (E)-3-[5-(3,5-Dichloro-2-propyl-phenoxy)-pentyloxy]-6-hydroxymethyl-2-propenyl-4H-pyran-4-one (EHT 9916)    2-Hydroxymethyl-5-(5-indol-1-yl-pentyloxy)-4H-pyran-4-one (EHT 6353)    Ethyl-carbamic acid 5-(5-indol-1-yl-pentyloxy)-4-oxo-4H-pyran-2-ylmethyl ester (EHT 1120)    Cyclohexyl-carbamic acid 5-(5-indol-1-yl-pentyloxy)-4-oxo-4H-pyran-2-ylmethyl ester (EHT 6231)    Phenyl-carbamic acid 5-(5-indol-1-yl-pentyloxy)-4-oxo-4H-pyran-2-ylmethyl ester (EHT 4902)    (4-Chloro-phenyl)-carbamic acid 5-(5-indol-1-yl-pentyloxy)-4-oxo-4H-pyran-2-ylmethyl ester (EHT 2232)    (4-Nitro-phenyl)-carbamic acid 5-(5-indol-1-yl-pentyloxy)-4-oxo-4H-pyran-2-ylmethyl ester (EHT 5332)    Butanoic acid 5-(5-indol-1-yl-pentyloxy)-4-oxo-4H-pyran-2-ylmethyl ester (EHT 1393)    Cyclohexanecarboxylic acid 5-(5-indol-1-yl-pentyloxy)-4-oxo-4H-pyran-2-ylmethyl ester (EHT 2253)    Phenyl-acetic acid 5-(5-indol-1-yl-pentyloxy)-4-oxo-4H-pyran-2-ylmethyl ester (EHT 2665)    Benzoic acid 5-(5-indol-1-yl-pentyloxy)-4-oxo-4H-pyran-2-ylmethyl ester (EHT 6517)    Furan-3-carboxylic acid 5-(5-indol-1-yl-pentyloxy)-4-oxo-4H-pyran-2-ylmethyl ester (EHT 4167)    4-Chloro-benzoic acid 5-(5-indol-1-yl-pentyloxy)-4-oxo-4H-pyran-2-ylmethyl ester (EHT 0078)    (E)-6-Hydroxymethyl-3-(5-indol-1-yl-pentyloxy)-2-propenyl-4H-pyran-4-one (EHT 7286)    5-(5-Indol-1-yl-pentyloxy)-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 7395)    5-(5-Phenylsulfanyl-pentyloxy)-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 1414)    2-Hydroxymethyl-5-(5-phenylsulfanyl-pentyloxy)-4H-pyran-4-one (EHT 2939)    5-(5-Phenoxy-pentyloxy)-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 6245)    2-Hydroxymethyl-5-(5-phenoxy-pentyloxy)-4H-pyran-4-one (EHT 1329)    5-[5-(5-Chloro-pyridin-2-yloxy)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 0696)    5-[5-(5-trifluoromethyl-pyridin-2-yloxy)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 1171)    5-[5-(3,4-Dimethoxy-phenylsulfanyl)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 3663)    4-Bromo-3-{5-[4-oxo-6-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-3-yloxy]-pentyloxy}-thiophene-2-carboxylic acid methyl ester (EHT 4408)    3-Cyclopropylmethoxy-4-{5-[4-oxo-6-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-3-yloxy]-pentyloxy}-benzoic acid ethyl ester (EHT 7565)    5-[5-(4-Butoxy-3-nitro-phenylamino)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 5230)    5-[5-(4-Acetyl-3-ethylamino-2-propyl-phenoxy)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 9411)    N-(3-{5-[4-Oxo-6-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-3-yloxy]-pentyloxy}-4-propyl-phenyl)-acetamide (EHT 7151)    5-[5-(6-Acetyl-3-ethylamino-2-propyl-phenoxy)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 7096)    5-[5-(2-Phenyl-indol-1-yl)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 9013)    5-[5-(4-Acetyl-3-amino-2-propyl-phenoxy)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 5769)    5-[5-(2,5-Dimethyl-furan-3-ylsulfanyl)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 7976)    5-[5-(2,4-Dimethyl-pyrido[2,3-b]indol-9-yl)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 6448)    5-[5-(2-Methyl-indol-1-yl)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 2427)    5-(5-pyrrolo[2,3-b]pyridin-1-yl-pentyloxy)-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 8309)    5-[5-(5,6-Dimethoxy-indol-1-yl)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 5457)    5-[5-(6-Methoxy-indol-1-yl)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 5235)    5-[5-(6-Chloro-indol-1-yl)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 8617)    5-[5-(4-Methoxy-indol-1-yl)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 0091)    5-[5-(5-Methoxy-indol-1-yl)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 8140)    5-[5-(2,4-Dimethyl-5,6,7,8-tetrahydro-pyrido[2,3-b]indol-9-yl)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 7337)    5-[5-(3,4-Dichloro-phenylsulfanyl)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 0407)    5-[5-(5-Chloro-indol-1-yl)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 0823)    5-[5-(5-Fluoro-indol-1-yl)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 0533)    5-[5-(2-Methoxy-4-propyl-phenoxy)-pentyloxy]-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 9387)    5-[2-Indol-1-yl-ethoxy)-2-(tetrahydro-pyran-2-yloxymethyl)]-4H-pyran-4-one (EHT 7599)    5-(3-Indoyl-1-yl-propoxy)-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 4283)    5-(4-Indol-1-yl-butoxy)-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 5741)    2-Hydroxymethyl-5-(4-indol-1-yl-butoxy)-4H-pyran-4-one (EHT 3089)    5-(4-Indol-1-yl-(trans)-but-2-enyloxy)-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 6895)    2-Hydroxymethyl-5-(5-indol-1-yl-pentyloxy)-4H-pyran-4-one (EHT 6353)    5-(5-Indol-1-yl-hexyloxy)-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 2358)    5-(8-Indol-1-yl-heptyloxy)-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 8733)    5-(8-Indol-1-yl-octyloxy)-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 2271)    5-[5-(5-Chloro-indol-1-yl)-pentyloxy]-2-hydroxymethyl-4H-pyran-4-one (EHT 9238)    5-[5-(2,3-Dihydro-indol-1-yl)-pentyloxy]-2-hydroxymethyl-4H-pyran-4-one (EHT 8650)    5-[5-(6-Chloro-purin-9-yl)-pentyloxy]-2-hydroxymethyl-4H-pyran-4-one (EHT 0248)    2-Hydroxymethyl-5-[5-(3-methyl-indol-1-yl)-pentyloxy]-4H-pyran-4-one (EHT 3065)    5-[5-(5-fluoro-indol-1-yl)-pentyloxy]-2-Hydroxymethyl-4H-pyran-4-one (EHT 9546)    5-[5-(6-chloro-indol-1-yl)-pentyloxy]-2-Hydroxymethyl-4H-pyran-4-one (EHT 9853)    5-[3-Indol-1-yl-methyl-benzyloxy)-2-tetrahydro-pyran-2-yloxymethyl)]-4H-pyran-4-one (EHT 8589)    5-[4-Indol-1-yl-methyl-benzyloxy)-2-tetrahydro-pyran-2-yloxymethyl)]-4H-pyran-4-one (EHT 3986)    5-(2-Indol-1-ylmethyl-benzyloxy)-2-(tetrahydro-pyran-2-yloxymethyl)-4H-pyran-4-one (EHT 4336).    
     
     
         38 . A pharmaceutical composition comprising at least one compound according to  claim 22  and a pharmaceutically acceptable vehicle or support.  
     
     
         39 . A composition comprising at least one compound according to  claim 22  and a pharmaceutically acceptable vehicle or support, for the treatment of a disease associated with abnormal cell proliferation.  
     
     
         40 . A method for the treatment of a disease associated with abnormal cell proliferation, wherein an effective amount of at least one compound of formula (I) is administered to a person in need of such treatment, and wherein compound is of the following formula (I):  
       
         
           
           
               
               
           
         
         R 1  is CH 2 R 3  or COR 3 ;  
         R 2  represents a hydrogen atom or an alkenyl group containing from 3 to 6 carbon atoms;  
         R 3  is —OH, —OR 4 , —SR 4 , —NR 5 R 6 , or  
         
           
             
             
                 
                 
             
           
         
         R 4  represents a group selected from alkyl containing from 1 to 6 carbon atoms, a cycloalkyl group a radical —CONR 5 R 6 , aryl, a 5- to 12-membered heterocyclic ring which has 1 to 3 hetero-atoms selected from oxygen, sulfur and nitrogen, heteroaryl, aralkyl, heteroaralkyl, alkanoyl or cycloalkanoyl from 2 to 6 carbon atoms, arylcarbonyl, heteroarylcarbonyl, arylalkanoyl and heteroarylalkanoyl;  
         R 5  and R 6 , independently from each other, are selected from a hydrogen atom, an alkyl group having from 1 to 10 carbon atoms, an aryl and an aralkyl;  
         m is 2 or 3;  
         “linker” represents (CH 2 ) n , wherein n represents an integer between 1 and 10 inclusive or a xylenyl group (meta, para or ortho);  
         Y represents an oxygen atom, a sulfur atom or a radical —NR 7 —;  
         R 7 , identical or different, is selected from a group consisting of a hydrogen atom, an alkyl group having from 1 to 10 carbon atoms, an aryl and an aralkyl; 
 either:  
 
         X represents an oxygen atom, a sulfur atom or a radical —NR 7 —;  
         A represents either a substituted phenyl group of formula  
         
           
             
             
                 
                 
             
           
         
          in which:  
         R 8 , R 9 , R 10  and R 11 , independently from each other, are selected from a hydrogen atom, a halogen atom (preferably F, Cl, or Br), a hydroxyl group, a (C 1 -C 10 )alkyl group, an alkenyl group, an (C 1 -C 10 )alkanoyl group, a (C 1 -C 10 )alkoxy group, a (C 1 -C 10 )alkoxycarbonyl group, an aryl group, an aralkyl group, an arylcarbonyl group, a mono- or poly-cyclic hydrocarbon group, a —NHCO(C 1 -C 6 )alkyl group, —NO 2 , —CN, a —NR 12 R 13  group or a trifluoro(C 1 -C 6 )alkyl group; preferably R 8 , R 9 , R 10  and R 11 , not being simultaneously hydrogen atom,  
         or alternatively two substituents, R 8  and R 9 , may form together a mono- or poly-cyclic hydrocarbon group with the carbon atoms of the phenyl group they are attached and the two other substituents, R 10  and R 11 , are as defined above;  
         or A represents a 5- to 12-membered heterocyclic ring which has 1 to 3 hetero-atoms selected from oxygen, sulfur and nitrogen, said ring is bonded directly to X;  
         R 12  and R 13 , independently from each other, are selected in the group consisting of a hydrogen atom, an alkyl group having from 1 to 10 carbon atoms, an aryl and an aralkyl; 
 or X-A represents a group of formula (II):  
                     
  wherein:  
 
         R 14 , R 15 , R 16 , R 17 , R 18  and R 19 , independently from each other, represent a hydrogen atom, a halogen atom (preferably F, Cl, or Br), a hydroxyl group, a (C 1 -C 10 )alkyl group, an (C 1 -C 10 )alkanoyl group, a (C 1 -C 10 )alkoxy group, an aryl group, an aralkyl group, an arylcarbonyl group, a mono- or poly-cyclic hydrocarbon group, —NO 2 , —CN, a —NR 12 R 13  group or a trifluoro(C 1 -C 6 )alkyl group, R 12  and R 13  being as defined above; alternatively, R 14  and R 15  may form together with the bond they, are attached thereto a cycloalkyl group (preferably a cyclohexyl group) or an aryl group (preferably a phenyl group);  
         W represents a carbon or nitrogen atom;  
         Z represents a carbon or nitrogen atom.  
       
     
     
         41 . A method according to  claim 40 , wherein diseases associated with abnormal cell proliferation are cancers or restenosis.  
     
     
         42 . A method according to  claim 40 , wherein diseases associated with abnormal cell proliferation are cancers selected in the group consisting of prostate cancer, ovarian cancer, pancreas cancer, lung cancer, breast cancer, liver cancer, head and neck cancer, colon cancer, bladder cancer, non-Hodgkin 's lymphoma cancer and melanoma.