Urea derivatives, methods for their manufacture, and uses therefor

Abstract

The present invention provides compounds of formula (I): in which R 1 , R′ 1 , R 2 , R′ 2 , R 3 , and Y have the meanings given in the description, to a process for their preparation, their application by way of medicaments, and to pharmaceutical compositions containing them.

1 . A method for treatment of diseases or disorders linked to abnormal physiological behaviour of inorganic ion receptors which comprises administration to a patient in need thereof of an effective amount of a compound of formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 Y is oxygen or sulphur; 
 R 1  and R′ 1  are the same or different, and each represents an aryl group, a heteroaryl group, or R 1  and R′ 1 , together with the carbon atom to which they are linked, form a fused ring structure of formula: 
 
       
         
           
           
               
               
           
         
       
       in which A represents a single bond, a methylene group, a dimethylene group, oxygen, nitrogen or sulphur, said sulphur optionally being in the sulphoxide or sulphone forms, 
       wherein each of R 1  and R′ 1 , or said fused ring structure formed thereby, is optionally substituted by at least one substituent selected from the group c,
 wherein the group c consists of: halogen atoms; hydroxyl groups; carboxyl groups; linear and branched alkyl, hydroxyalkyl, haloalkyl, alkylthio, alkenyl, and alkynyl groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; hydroxycarbonylalkyl, alkylcarbonyl, alkoxycarbonylalkyl, and alkoxycarbonyl groups; trifluoromethyl, and trifluoromethoxyl groups; —CN groups; —NO 2  groups; and alkylsulphonyl groups optionally in the sulphoxide or sulphone forms; wherein any alkyl component has from 1 to 6 carbon atoms, and any alkenyl or alkynyl components have from 2 to 6 carbon atoms, and wherein, when there is more than one substituent, then each said substituent is the same or different, 
 R 2  and R′ 2 , which may be the same or different, each represents: a hydrogen atom; a linear or branched alkyl group containing from 1 to 6 carbon atoms and optionally substituted by at least one halogen atom, hydroxy or alkoxy group containing from 1 to 6 carbon atoms; or an alkylaminoalkyl or dialkylaminoalkyl group wherein each alkyl group contains from 1 to 6 carbon atoms, 
 or R 2  and R′ 2 , together with the nitrogen atom to which they are linked, form a saturated or unsaturated heterocycle containing 0, 1 or 2 additional heteroatoms and having 5, 6, or 7 ring atoms, said heterocycle being optionally substituted by at least one substituent selected from the group c defined above, 
 and wherein, when there is more than one substituent, said substituent is the same or different, 
 R 3  represents a group of formula: 
 
       
         
           
           
               
               
           
         
       
       in which B represents an oxygen atom or a sulphur atom, x is 0, 1 or 2, y and y′ are the same or different, and each is 0 or 1, Ar and Ar′ are the same or different and each represents an aryl or heteroaryl group, n and n′ are the same or different, and each is 1, when the y or y′ with which it is associated is 0, or is equal to the number of positions that can be substituted on the associated Ar or Ar′, when the said y or y′ is 1, the fused ring containing N x  is a five- or six-membered heteroaryl ring, and wherein R and R′, which may be the same or different, each represent a hydrogen atom or a substituent selected from the group a,
 wherein the group a consists of: halogen atoms; hydroxyl groups; carboxyl groups; aldehyde groups; linear and branched alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, haloalkyl, haloalkenyl, and haloalkynyl groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; aralkoxy groups; aryloxy groups; alkoxycarbonyl, aralkoxycarbonyl, aryloxycarbonyl, hydroxycarbonylalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, and aryloxycarbonylalkyl groups; perfluoralkyl and perfluoroalkoxy groups; —CN groups; acyl groups; amino, alkylamino, aralkylamino, arylamino, dialkylamino, diaralkylamino, diarylamino, acylamino, and diacylamino groups; alkoxycarbonylamino, aralkoxycarbonylamino, aryloxycarbonylamino, alkylcarbonylamino, aralkylcarbonylamino, and arylcarbonylamino groups; alkylaminocarbonyloxy, aralkylaminocarbonyloxy, and arylaminocarbonyloxy groups; alkyl groups substituted with an amino, alkylamino, aralkylamino, arylamino, dialkylamino, diaralkylamino, diarylamino, acylamino, trifluoromethylcarbonylamino, fluoroalkylcarbonylamino, or diacylamino group; —CONH 2  groups; alkyl-, aralkyl-, and aryl-amido groups; alkylthio, arylthio and aralkylthio groups and the oxidised sulphoxide and sulphone forms thereof; sulphonyl, alkylsulphonyl, haloalkylsulphonyl, arylsulphonyl and aralkylsulphonyl groups; sulphonamide, alkylsulphonamide, haloalkylsulphonamide, di(alkylsulphonyl)amino, aralkylsulphonamide, di(aralkylsulphonyl)amino, arylsulphonamide, and di(arylsulphonyl)amino groups; and saturated and unsaturated heterocyclyl groups, said heterocyclyl groups being mono- or bi-cyclic and being optionally substituted by one or more substituents, which may be the same or different, selected from the group b, 
 wherein the group b consists of: halogen atoms; hydroxyl groups; carboxyl groups; aldehyde groups; linear and branched alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, haloalkyl, haloalkenyl, and haloalkynyl groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; alkoxycarbonyl, hydroxycarbonylalkyl and alkoxycarbonylalkyl groups; perfluoroalkyl and perfluoroalkoxy groups; —CN groups; acyl groups; amino, alkylamino, dialkylamino, acylamino, and diacylamino groups; alkyl groups substituted with an amino, alkylamino, dialkylamino, acylamino, or diacylamino group; —CONH 2  groups; alkylamido groups; alkylthio groups and the oxidised sulphoxide and sulphone forms thereof; sulphonyl, and alkylsulphonyl groups; and sulphonamide, alkylsulphonamide, and di(alkylsulphonyl)amino groups, 
 
       wherein, in groups a and b, any alkyl components contain from 1 to 6 carbon atoms, and any alkenyl or alkynyl components contain from 2 to 6 carbon atoms, and are optionally substituted by at least one halogen atom or hydroxy group, and wherein any aryl component is optionally a heteroaryl group, 
       and salts and esters thereof. 
     
     
         2 . The method of  claim 1 , wherein the inorganic ion receptor is a calcium receptor. 
     
     
         3 . The method of  claim 2 , wherein the calcium receptor is expressed in the parathyroid, the thyroid, the bone cells, the renal cells, the lung, the brain, the pituitary gland, the hypothalamus, the gastrointestinal cells, the pancreas cells, the skin cells, the cells of the central or peripheral nervous system and the smooth muscle cells. 
     
     
         4 . The method of  claim 1 , wherein Y is oxygen. 
     
     
         5 . The method of  claim 1 , wherein R 1  and R′ 1  are the same or different, and each represents a monocyclic aryl group, a monocyclic heteroaryl group, or R 1  and R′ 1 , together with the carbon atom to which they are linked, form a fused ring structure of formula: 
       
         
           
           
               
               
           
         
       
       wherein each of R 1  and R′ 1 , or said fused ring structure formed thereby, is optionally substituted by at least one substituent selected from the group c. 
     
     
         6 . The method of  claim 1 , wherein any alkyl, alkenyl or alkynyl component has no more than 4 carbon atoms. 
     
     
         7 . The method of  claim 1 , wherein any alkylsulphonyl substituent is a methylsulphonyl substituent. 
     
     
         8 . The method of  claim 1 , wherein the compound is of formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 Y is oxygen; 
 R 1  and R′ 1  each represent phenyl, wherein each of R 1  and R′ 1 , is optionally substituted by at least one substituent selected from the group c,
 wherein the group c consists of: halogen atoms; hydroxyl groups; carboxyl groups; linear and branched alkyl, hydroxyalkyl, haloalkyl, alkylthio, alkenyl, and alkynyl groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; hydroxycarbonylalkyl groups; alkylcarbonyl groups; alkoxycarbonylalkyl groups; alkoxycarbonyl groups; trifluoromethyl groups; trifluoromethoxyl groups; —CN groups; —NO 2  groups; and alkylsulphonyl groups optionally in the sulphoxide or sulphone forms; wherein any alkyl component has from 1 to 6 carbon atoms, and any alkenyl or alkynyl components have from 2 to 6 carbon atoms, 
 
 
       and wherein, when there is more than one substituent, then each said substituent is the same or different;
 R 2  and R′ 2 , together with the nitrogen atom to which they are linked, form an morpholinyl group optionally substituted by at least one substituent selected from the group c defined above, 
 
       and wherein, when there is more than one substituent, said substituent is the same or different;
 R 3  represents a group of formula: 
 
       
         
           
           
               
               
           
         
       
       in which B represents an oxygen atom or a sulphur atom; x is 0, 1 or 2, y and y′ are the same or different, and each is 0 or 1; Ar and Ar′ are the same or different and each represents an aryl or heteroaryl group; n and n′ are the same or different, and each is 1, when the y or y′ with which it is associated is 0, or is equal to the number of positions that can be substituted on the associated Ar or Ar′, when the said y or y′ is 1; the fused ring containing N x  is a five- or six-membered heteroaryl ring; and wherein R and R′, which may be the same or different, each represent a hydrogen atom or a substituent selected from the group a,
 wherein the group a consists of: halogen atoms; hydroxyl groups; carboxyl groups; aldehyde groups; linear and branched alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, haloalkyl, haloalkenyl, and haloalkynyl groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; aralkoxy groups; aryloxy groups; alkoxycarbonyl, aralkoxycarbonyl, aryloxycarbonyl, hydroxycarbonylalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, and aryloxycarbonylalky groups; perfluoroalkyl and perfluoroalkoxy groups; —CN groups; acyl groups; amino, alkylamino, aralkylamino, arylamino, dialkylamino, diaralkylamino, diarylamino, acylamino, and diacylamino groups; alkoxycarbonylamino, aralkoxycarbonylamino, aryloxycarbonylamino, alkylcarbonylamino, aralkylcarbonylamino, and arylcarbonylamino groups; alkylaminocarbonyloxy, aralkylaminocarbonyloxy, and arylaminocarbonyloxy groups; alkyl groups substituted with an amino, alkylamino, aralkylamino, arylamino, dialkylamino, diaralkylamino, diarylamino, acylamino, trifluoromethylcarbonyl-amino, fluoroalkylcarbonylamino, or diacylamino group; —CONH 2  groups; alkyl-, aralkyl-, and aryl-amido groups; alkylthio, arylthio and aralkylthio groups and the oxidised sulphoxide and sulphone forms thereof; sulphonyl, alkylsulphonyl, haloalkylsulphonyl, arylsulphonyl and aralkylsulphonyl groups; sulphonamide, alkylsulphonamide, haloalkylsulphonamide, di(alkylsulphonyl)amino, aralkylsulphonamide, di(aralkylsulphonyl)amino, arylsulphonamide, and di(arylsulphonyl)amino groups; and saturated and unsaturated heterocyclyl groups, said heterocyclyl groups being mono- or bi-cyclic and being optionally substituted by one or more substituents, which may be the same or different, selected from the group b,
 wherein the group b consists of: halogen atoms; hydroxyl groups; carboxyl groups; aldehyde groups; linear and branched alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, haloalkyl, haloalkenyl, and haloalkynyl groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; alkoxycarbonyl, hydroxycarbonylalkyl, and alkoxycarbonylalkyl groups; perfluoroalkyl; perfluoroalkoxy; —CN groups; acyl groups; amino, alkylamino, dialkylamino, acylamino, and diacylamino groups; alkyl groups substituted with an amino, alkylamino, dialkylamino, acylamino, or diacylamino group; —CONH 2  groups; alkylamido groups; alkylthio groups and the oxidised sulphoxide and sulphone forms thereof; sulphonyl, and alkylsulphonyl groups; and sulphonamide, alkylsulphonamide, and di(alkylsulphonyl)amino groups; 
 
 wherein, in groups a and b, any alkyl components contain from 1 to 6 carbon atoms, and any alkenyl or alkynyl components contain from 2 to 6 carbon atoms, and are optionally substituted by at least one halogen atom or hydroxy group, and wherein any aryl component is optionally a heteroaryl group, 
 
       and salts and esters thereof. 
     
     
         9 . The method of  claim 1 , wherein the compound is selected from the group consisting of:
 3-(6-chlorobenzothiazol-2-yl)-1-(3,3-diphenylpropyl)-1-(2-morpholin-4-ylethyl)-urea and the dihydrochloride thereof,   1-(3,3-diphenylpropyl)-3-(6-methoxybenzothiazol-2-yl)-1-(2-morpholin-4-ylethyl)-urea,   1-(3,3-diphenylpropyl)-3-(4-methoxybenzothiazol-2-yl)-1-(2-morpholin-4-ylethyl)-urea,   3-(4-chlorobenzothiazol-2-yl)-1-(3,3-diphenylpropyl)-1-(2-morpholin-4-ylethyl)-urea and the dihydrochloride thereof,   3-benzothiazol-2-yl-1-(3,3-diphenylpropyl)-1-(2-morpholin-4-ylethyl)-urea and the dihydrochloride thereof,   1-(3,3-diphenylpropyl)-3-(5-methoxythiazolo[5,4-b]pyridin-2-yl)-1-(2-morpholin-4-ylethyl)-urea,   1-(3,3-diphenylpropyl)-1-(2-morpholin-4-ylethyl)-3-(4-oxazol-2-ylphenyl)urea and the dihydrochloride thereof,   3-[4-(4-chlorophenyl)thiazol-2-yl]-1-[3,3-d]phenylpropyl)-1-(2-morpholin-4-ylethyl)-urea and the dihydrochloride thereof,   1-(3,3-diphenylpropyl)-1-(2-morpholin-4-ylethyl)-3-(4-12-tolylthiazol-2-yl)urea and the dihydrochloride thereof,   5-{2-[3-(3,3-diphenylpropyl)-3-(2-morpholin-4-ylethyl)ureido]thiazol-4-yl}-isoxazole-3-carboxylic acid ethyl ester and the dihydrochloride thereof,   1-(3,3-diphenylpropyl)-1-(2-morpholin-4-ylethyl)-3-[4-(4-pyrrolidin-1-ylphenyl)-thiazol-2yl]urea and the trihydrochloride thereof,   1-(3,3-diphenylpropyl)-1-(2-morpholin-4-ylethyl)-3-[4-(4-morpholin-4-ylphenyl)-thiazol-2yl]urea,   3-[4-(4-cyanophenyl)thiazol-2-yl]-1-(3,3-diphenylpropyl)-1-(2-morpholin-4-ylethyl)-urea and the dihydrochloride thereof,   1-(3,3-diphenylpropyl)-1-(2-morpholin-4-ylethyl)-3-(4-pyridin-2-ylthiazol-2-yl)urea,   1-(3,3-diphenylpropyl)-1-(2-morpholin-4-ylethyl)-3-(4-pyridin-3-ylthiazol-3-yl)urea and the trihydrochloride thereof,   1-(3,3-diphenylpropyl)-1-(2-morpholin-4-ylethyl)-3-[4-(2-oxo-2,3-dihydro-benzoxazol-6yl) thiazol-2-yl]urea,   1-(3,3-diphenylpropyl)-3-[4-(4-(fluorophenyl)-5-methylthiazol-2-yl]-1-(2-morpholin-4-ylethyl)urea and the hydrochloride thereof,   1-(3,3-diphenylpropyl)-3-[4-(4-(fluorophenyl)thiazol-2-yl]-1-(2-morpholin-4-ylethyl)urea,   1-(3,3-diphenylpropyl)-3-[4-(5-methylfuran-2-yl)thiazol)-2-yl]-1-(2-morpholin-4-ylethyl)urea and the dihydrochloride thereof,   N-(4-{2-[3-(3,3-diphenylpropyl)-3-(2-morpholin-4-ylethyl)ureido]thiazol-4-ylphenyl)]methanesulphonamide and the dihydrochloride thereof,   3-benzothiazol-2-yl-1-(2-morpholin-4-ylethyl)-1-(3-phenyl-3-pyridin-4-ylpropyl)-urea,   1-(2-morpholin-4-ylethyl)-1-(3-phenyl-3-pyridin-4-ylpropyl)-3-(4-phenylthiazol-2-yl)urea,   N-(4-{2-[3-(3,3-diphenylpropyl)-3-(2-morpholin-4-ylethyl)ureido]-[4-thiazol-4-yl}phenyl)acetamide,   1-(3,3-diphenylpropyl)-3-[4-(4-methoxyphenyl)thiazol-2-yl]-1-(2-morpholin-4-ylethyl)urea and the dihydrochloride thereof,   1-(3,3-diphenylpropyl)-3-[4-(4-methanesulphonylphenyl)thiazol-2-yl]-1-(2-morpholin-4-ylethyl)urea and the dihydrochloride thereof,   1-(3,3-diphenylpropyl)-3-[4-(4-fluorophenyl)thiazol-2-yl]-1-(2-morpholin-4-ylethyl)urea and the dihydrochloride thereof,   3-benzothiazol-2-yl-1-(3,3-diphenylpropyl)-1-(2-thiomorpholin-4-ylethyl)urea,   1-(3,3-diphenylpropyl)-3-(4-phenylthiazol-2-yl)-1-(2-thiomorpholin-4-ylethyl)urea,   3-benzothiazol-2-yl-1-[2-(2,6-dimethylmorpholin-4-yl)ethyl]-1-(3,3-diphenylpropyl)urea,   1-[2-(2,6-dimethylmorpholin-4-yl)ethyl]-1-(3,3-diphenylpropyl)-3-(4-phenylthiazol-2-yl)-urea,   1-(3,3-dithiophen-2-ylpropyl)-1-(2-morpholin-4-ylethyl)-3-(4-phenylthiazol-2-yl)urea, and   3-benzothiazol-2-yl-1-(3,3-dithiophen-2-ylpropyl)-1-(2-morpholin-4-ylethyl)urea.   
     
     
         10 . A method for treatment of cancer which comprises administration to a patient in need thereof of an effective amount of a compound of formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 Y is oxygen or sulphur; 
 R 1  and R′ 1  are the same or different, and each represents an aryl group, a heteroaryl group, or R 1  and R′ 1 , together with the carbon atom to which they are linked, form a fused ring structure of formula: 
 
       
         
           
           
               
               
           
         
         in which A represents a single bond, a methylene group, a dimethylene group, oxygen, nitrogen or sulphur, said sulphur optionally being in the sulphoxide or sulphone forms, 
       
       wherein each of R 1  and R′ 1 , or said fused ring structure formed thereby, is optionally substituted by at least one substituent selected from the group c,
 wherein the group c consists of: halogen atoms; hydroxyl groups; carboxyl groups; linear and branched alkyl, hydroxyalkyl, haloalkyl, alkylthio, alkenyl, and alkynyl groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; hydroxycarbonylalkyl, alkylcarbonyl, alkoxycarbonylalkyl, and alkoxycarbonyl groups; trifluoromethyl, and trifluoromethoxyl groups; —CN groups; —NO 2  groups; and alkylsulphonyl groups optionally in the sulphoxide or sulphone forms; wherein any alkyl component has from 1 to 6 carbon atoms, and any alkenyl or alkynyl components have from 2 to 6 carbon atoms, and wherein, when there is more than one substituent, then each said substituent is the same or different, 
 R 2  and R′ 2 , which may be the same or different, each represents: a hydrogen atom; a linear or branched alkyl group containing from 1 to 6 carbon atoms and optionally substituted by at least one halogen atom, hydroxy or alkoxy group containing from 1 to 6 carbon atoms; or an alkylaminoalkyl or dialkylaminoalkyl group wherein each alkyl group contains from 1 to 6 carbon atoms, 
 or R 2  and R′ 2 , together with the nitrogen atom to which they are linked, form a saturated or unsaturated heterocycle containing 0, 1 or 2 additional heteroatoms and having 5, 6, or 7 ring atoms, said heterocycle being optionally substituted by at least one substituent selected from the group c defined above, 
 and wherein, when there is more than one substituent, said substituent is the same or different, 
 R 3  represents a group of formula: 
 
       
         
           
           
               
               
           
         
       
       in which B represents an oxygen atom or a sulphur atom, x is 0, 1 or 2, y and y′ are the same or different, and each is 0 or 1, Ar and Ar′ are the same or different and each represents an aryl or heteroaryl group, n and n′ are the same or different, and each is 1, when the y or y′ with which it is associated is 0, or is equal to the number of positions that can be substituted on the associated Ar or Ar′, when the said y or y′ is 1, the fused ring containing N x  is a five- or six-membered heteroaryl ring, and wherein R and R′, which may be the same or different, each represent a hydrogen atom or a substituent selected from the group a,
 wherein the group a consists of: halogen atoms; hydroxyl groups; carboxyl groups; aldehyde groups; linear and branched alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, haloalkyl, haloalkenyl, and haloalkynyl groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; aralkoxy groups; aryloxy groups; alkoxycarbonyl, aralkoxycarbonyl, aryloxycarbonyl, hydroxycarbonylalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, and aryloxycarbonylalkyl groups; perfluoralkyl and perfluoroalkoxy groups; —CN groups; acyl groups; amino, alkylamino, aralkylamino, arylamino, dialkylamino, diaralkylamino, diarylamino, acylamino, and diacylamino groups; alkoxycarbonylamino, aralkoxycarbonylamino, aryloxycarbonylamino, alkylcarbonylamino, aralkylcarbonylamino, and arylcarbonylamino groups; alkylaminocarbonyloxy, aralkylaminocarbonyloxy, and arylaminocarbonyloxy groups; alkyl groups substituted with an amino, alkylamino, aralkylamino, arylamino, dialkylamino, diaralkylamino, diarylamino, acylamino, trifluoromethylcarbonylamino, fluoroalkylcarbonylamino, or diacylamino group; —CONH 2  groups; alkyl-, aralkyl-, and aryl-amido groups; alkylthio, arylthio and aralkylthio groups and the oxidised sulphoxide and sulphone forms thereof; sulphonyl, alkylsulphonyl, haloalkylsulphonyl, arylsulphonyl and aralkylsulphonyl groups; sulphonamide, alkylsulphonamide, haloalkylsulphonamide, di(alkylsulphonyl)amino, aralkylsulphonamide, di(aralkylsulphonyl)amino, arylsulphonamide, and di(arylsulphonyl)amino groups; and saturated and unsaturated heterocyclyl groups, said heterocyclyl groups being mono- or bi-cyclic and being optionally substituted by one or more substituents, which may be the same or different, selected from the group b, 
 wherein the group b consists of: halogen atoms; hydroxyl groups; carboxyl groups; aldehyde groups; linear and branched alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, haloalkyl, haloalkenyl, and haloalkynyl groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; alkoxycarbonyl, hydroxycarbonylalkyl and alkoxycarbonylalkyl groups; perfluoroalkyl and perfluoroalkoxy groups; —CN groups; acyl groups; amino, alkylamino, dialkylamino, acylamino, and diacylamino groups; alkyl groups substituted with an amino, alkylamino, dialkylamino, acylamino, or diacylamino group; —CONH 2  groups; alkylamido groups; alkylthio groups and the oxidised sulphoxide and sulphone forms thereof; sulphonyl, and alkylsulphonyl groups; and sulphonamide, alkylsulphonamide, and di(alkylsulphonyl)amino groups, 
 wherein, in groups a and b, any alkyl components contain from 1 to 6 carbon atoms, and any alkenyl or alkynyl components contain from 2 to 6 carbon atoms, and are optionally substituted by at least one halogen atom or hydroxy group, and wherein any aryl component is optionally a heteroaryl group, 
 
       and salts and esters thereof. 
     
     
         11 . The method of  claim 10 , wherein the cancer is cancer of the parathyroid or the digestive tract. 
     
     
         12 . A method for treatment of neurodegenerative diseases which comprises administration to a patient in need thereof of an effective amount of a compound of formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 Y is oxygen or sulphur; 
 R 1  and R′ 1  are the same or different, and each represents an aryl group, a heteroaryl group, or R 1  and R′ 1 , together with the carbon atom to which they are linked, form a fused ring structure of formula: 
 
       
         
           
           
               
               
           
         
         in which A represents a single bond, a methylene group, a dimethylene group, oxygen, nitrogen or sulphur, said sulphur optionally being in the sulphoxide or sulphone forms, 
       
       wherein each of R 1  and R′ 1 , or said fused ring structure formed thereby, is optionally substituted by at least one substituent selected from the group c,
 wherein the group c consists of: halogen atoms; hydroxyl groups; carboxyl groups; linear and branched alkyl, hydroxyalkyl, haloalkyl, alkylthio, alkenyl, and alkynyl groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; hydroxycarbonylalkyl, alkylcarbonyl, alkoxycarbonylalkyl, and alkoxycarbonyl groups; trifluoromethyl, and trifluoromethoxyl groups; —CN groups; —NO 2  groups; and alkylsulphonyl groups optionally in the sulphoxide or sulphone forms; wherein any alkyl component has from 1 to 6 carbon atoms, and any alkenyl or alkynyl components have from 2 to 6 carbon atoms, and wherein, when there is more than one substituent, then each said substituent is the same or different, 
 R 2  and R′ 2 , which may be the same or different, each represents: a hydrogen atom; a linear or branched alkyl group containing from 1 to 6 carbon atoms and optionally substituted by at least one halogen atom, hydroxy or alkoxy group containing from 1 to 6 carbon atoms; or an alkylaminoalkyl or dialkylaminoalkyl group wherein each alkyl group contains from 1 to 6 carbon atoms, 
 or R 2  and R′ 2 , together with the nitrogen atom to which they are linked, form a saturated or unsaturated heterocycle containing 0, 1 or 2 additional heteroatoms and having 5, 6, or 7 ring atoms, said heterocycle being optionally substituted by at least one substituent selected from the group c defined above, 
 and wherein, when there is more than one substituent, said substituent is the same or different, 
 R 3  represents a group of formula: 
 
       
         
           
           
               
               
           
         
       
       in which B represents an oxygen atom or a sulphur atom, x is 0, 1 or 2, y and y′ are the same or different, and each is 0 or 1, Ar and Ar′ are the same or different and each represents an aryl or heteroaryl group, n and n′ are the same or different, and each is 1, when the y or y′ with which it is associated is 0, or is equal to the number of positions that can be substituted on the associated Ar or Ar′, when the said y or y′ is 1, the fused ring containing N x  is a five- or six-membered heteroaryl ring, and wherein R and R′, which may be the same or different, each represent a hydrogen atom or a substituent selected from the group a,
 wherein the group a consists of: halogen atoms; hydroxyl groups; carboxyl groups; aldehyde groups; linear and branched alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, haloalkyl, haloalkenyl, and haloalkynyl groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; aralkoxy groups; aryloxy groups; alkoxycarbonyl, aralkoxycarbonyl, aryloxycarbonyl, hydroxycarbonylalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, and aryloxycarbonylalkyl groups; perfluoralkyl and perfluoroalkoxy groups; —CN groups; acyl groups; amino, alkylamino, aralkylamino, arylamino, dialkylamino, diaralkylamino, diarylamino, acylamino, and diacylamino groups; alkoxycarbonylamino, aralkoxycarbonylamino, aryloxycarbonylamino, alkylcarbonylamino, aralkylcarbonylamino, and arylcarbonylamino groups; alkylaminocarbonyloxy, aralkylaminocarbonyloxy, and arylaminocarbonyloxy groups; alkyl groups substituted with an amino, alkylamino, aralkylamino, arylamino, dialkylamino, diaralkylamino, diarylamino, acylamino, trifluoromethylcarbonylamino, fluoroalkylcarbonylamino, or diacylamino group; —CONH 2  groups; alkyl-, aralkyl-, and aryl-amido groups; alkylthio, arylthio and aralkylthio groups and the oxidised sulphoxide and sulphone forms thereof; sulphonyl, alkylsulphonyl, haloalkylsulphonyl, arylsulphonyl and aralkylsulphonyl groups; sulphonamide, alkylsulphonamide, haloalkylsulphonamide, di(alkylsulphonyl)amino, aralkylsulphonamide, di(aralkylsulphonyl)amino, arylsulphonamide, and di(arylsulphonyl)amino groups; and saturated and unsaturated heterocyclyl groups, said heterocyclyl groups being mono- or bi-cyclic and being optionally substituted by one or more substituents, which may be the same or different, selected from the group b, 
 wherein the group b consists of: halogen atoms; hydroxyl groups; carboxyl groups; aldehyde groups; linear and branched alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, haloalkyl, haloalkenyl, and haloalkynyl groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; alkoxycarbonyl, hydroxycarbonylalkyl and alkoxycarbonylalkyl groups; perfluoroalkyl and perfluoroalkoxy groups; —CN groups; acyl groups; amino, alkylamino, dialkylamino, acylamino, and diacylamino groups; alkyl groups substituted with an amino, alkylamino, dialkylamino, acylamino, or diacylamino group; —CONH 2  groups; alkylamido groups; alkylthio groups and the oxidised sulphoxide and sulphone forms thereof; sulphonyl, and alkylsulphonyl groups; and sulphonamide, alkylsulphonamide, and di(alkylsulphonyl)amino groups, 
 wherein, in groups a and b, any alkyl components contain from 1 to 6 carbon atoms, and any alkenyl or alkynyl components contain from 2 to 6 carbon atoms, and are optionally substituted by at least one halogen atom or hydroxy group, and wherein any aryl component is optionally a heteroaryl group, 
 
       and salts and esters thereof. 
     
     
         13 . A method for treatment of a disease or condition which comprises administration to a patient in need thereof of an effective amount of a compound of formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 Y is oxygen or sulphur; 
 R 1  and R′ 1  are the same or different, and each represents an aryl group, a heteroaryl group, or R 1  and R′ 1 , together with the carbon atom to which they are linked, form a fused ring structure of formula: 
 
       
         
           
           
               
               
           
         
         in which A represents a single bond, a methylene group, a dimethylene group, oxygen, nitrogen or sulphur, said sulphur optionally being in the sulphoxide or sulphone forms, 
       
       wherein each of R 1  and R′ 1 , or said fused ring structure formed thereby, is optionally substituted by at least one substituent selected from the group c,
 wherein the group c consists of: halogen atoms; hydroxyl groups; carboxyl groups; linear and branched alkyl, hydroxyalkyl, haloalkyl, alkylthio, alkenyl, and alkynyl groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; hydroxycarbonylalkyl, alkylcarbonyl, alkoxycarbonylalkyl, and alkoxycarbonyl groups; trifluoromethyl, and trifluoromethoxyl groups; —CN groups; —NO 2  groups; and alkylsulphonyl groups optionally in the sulphoxide or sulphone forms; wherein any alkyl component has from 1 to 6 carbon atoms, and any alkenyl or alkynyl components have from 2 to 6 carbon atoms, and wherein, when there is more than one substituent, then each said substituent is the same or different, 
 R 2  and R′ 2  which may be the same or different, each represents: a hydrogen atom; a linear or branched alkyl group containing from 1 to 6 carbon atoms and optionally substituted by at least one halogen atom, hydroxy or alkoxy group containing from 1 to 6 carbon atoms; or an alkylaminoalkyl or dialkylaminoalkyl group wherein each alkyl group contains from 1 to 6 carbon atoms, 
 or R 2  and R′ 2 , together with the nitrogen atom to which they are linked, form a saturated or unsaturated heterocycle containing 0, 1 or 2 additional heteroatoms and having 5, 6, or 7 ring atoms, said heterocycle being optionally substituted by at least one substituent selected from the group c defined above, 
 and wherein, when there is more than one substituent, said substituent is the same or different, 
 R 3  represents a group of formula: 
 
       
         
           
           
               
               
           
         
       
       in which B represents an oxygen atom or a sulphur atom, x is 0, 1 or 2, y and y′ are the same or different, and each is 0 or 1, Ar and Ar′ are the same or different and each represents an aryl or heteroaryl group, n and n′ are the same or different, and each is 1, when the y or y′ with which it is associated is 0, or is equal to the number of positions that can be substituted on the associated Ar or Ar′, when the said y or y′ is 1, the fused ring containing N r  is a five- or six-membered heteroaryl ring, and wherein R and R′, which may be the same or different, each represent a hydrogen atom or a substituent selected from the group a,
 wherein the group a consists of: halogen atoms; hydroxyl groups; carboxyl groups; aldehyde groups; linear and branched alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, haloalkyl, haloalkenyl, and haloalkynyl groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; aralkoxy groups; aryloxy groups; alkoxycarbonyl, aralkoxycarbonyl, aryloxycarbonyl, hydroxycarbonylalkyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, and aryloxycarbonylalkyl groups; perfluoralkyl and perfluoroalkoxy groups; —CN groups; acyl groups; amino, alkylamino, aralkylamino, arylamino, dialkylamino, diaralkylamino, diarylamino, acylamino, and diacylamino groups; alkoxycarbonylamino, aralkoxycarbonylamino, aryloxycarbonylamino, alkylcarbonylamino, aralkylcarbonylamino, and arylcarbonylamino groups; alkylaminocarbonyloxy, aralkylaminocarbonyloxy, and arylaminocarbonyloxy groups; alkyl groups substituted with an amino, alkylamino, aralkylamino, arylamino, dialkylamino, diaralkylamino, diarylamino, acylamino, trifluoromethylcarbonylamino, fluoroalkylcarbonylamino, or diacylamino group; —CONH 2  groups; alkyl-, aralkyl-, and aryl-amido groups; alkylthio, arylthio and aralkylthio groups and the oxidised sulphoxide and sulphone forms thereof; sulphonyl, alkylsulphonyl, haloalkylsulphonyl, arylsulphonyl and aralkylsulphonyl groups; sulphonamide, alkylsulphonamide, haloalkylsulphonamide, di(alkylsulphonyl)amino, aralkylsulphonamide, di(aralkylsulphonyl)amino, arylsulphonamide, and di(arylsulphonyl)amino groups; and saturated and unsaturated heterocyclyl groups, said heterocyclyl groups being mono- or bi-cyclic and being optionally substituted by one or more substituents, which may be the same or different, selected from the group b,
 wherein the group b consists of: halogen atoms; hydroxyl groups; carboxyl groups; aldehyde groups; linear and branched alkyl, alkenyl, alkynyl, hydroxyalkyl, hydroxyalkenyl, hydroxyalkynyl, haloalkyl, haloalkenyl, and haloalkynyl groups; linear and branched alkoxyl groups; linear and branched thioalkyl groups; alkoxycarbonyl, hydroxycarbonylalkyl and alkoxycarbonylalkyl groups; perfluoroalkyl and perfluoroalkoxy groups; —CN groups; acyl groups; amino, alkylamino, dialkylamino, acylamino, and diacylamino groups; alkyl groups substituted with an amino, alkylamino, dialkylamino, acylamino, or diacylamino group; —CONH 2  groups; alkylamido groups; alkylthio groups and the oxidised sulphoxide and sulphone forms thereof; sulphonyl, and alkylsulphonyl groups; and sulphonamide, alkylsulphonamide, and di(alkylsulphonyl)amino groups, 
 
 wherein, in groups a and b, any alkyl components contain from 1 to 6 carbon atoms, and any alkenyl or alkynyl components contain from 2 to 6 carbon atoms, and are optionally substituted by at least one halogen atom or hydroxy group, and wherein any aryl component is optionally a heteroaryl group, 
 
       and salts and esters thereof; 
       wherein the disease or condition is abnormal calcium homeostasis, hyperplasia or parathyroid adenoma, intestinal malabsorption, biliary lithiasis or renal lithiasis ionised serum calcium level reduction during the treatment of hypercalcaemia cardiovascular diseases or hypertension. 
     
     
         14 . The method of  claim 13 , wherein the disease or condition is abnormal calcium homeostasis. 
     
     
         15 . The method of  claim 13 , wherein the disease or condition is hyperplasia or parathyroid adenoma. 
     
     
         16 . The method of  claim 13 , wherein the disease or condition is intestinal malabsorption. 
     
     
         17 . The method of  claim 13 , wherein the disease or condition is biliary lithiasis or renal lithiasis. 
     
     
         18 . The method of  claim 13 , wherein the disease or condition is ionised serum calcium level reduction during the treatment of hypercalcaemia. 
     
     
         19 . The method of  claim 13 , wherein the disease or condition is a cardiovascular disease. 
     
     
         20 . The method of  claim 13 , wherein the disease or condition is hypertension.