Urea derivatives, processes for their preparation, their use as medicaments, and pharmaceutical compositions containing them

A compound of formula (I):

• wherein:
• Y is oxygen or sulfur;
• R1 and R′1, are the same or different, and each represents an aryl group, a heteroaryl group, or R1 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 sulfur, said sulfur optionally being in the sulfoxide or sulfone forms,
• wherein each of R1 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, carboxyl, linear and branched alkyl, hydroxyalkyl, haloalkyl, thioalkyl, alkenyl, and alkynyl groups;
• linear and branched alkoxyl groups;
• linear and branched alkylthio groups;
• hydroxycarbonylalkyl;
• alkylcarbonyl;
• alkoxycarbonylalkyl;
• alkoxycarbonyl;
• trifluoromethyl;
• trifluoromethoxyl;
• —CN;
• —NO2;
• alkylsulfonyl groups optionally in the sulfoxide or sulfone 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,
• R2 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;
• an alkylaminoalkyl or dialkylaminoalkyl group wherein each alkyl group contains from 1 to 6 carbon atoms,
• or R2 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,
• R3 represents a group of formula —CH2)p—Ar—Rn,
• in which p is 0 or 1 and, when p is 1, (CH2)p may be substituted by methyl, chlorine, fluorine, hydroxy, or trimethyl, Ar represents an aryl or heteroaryl group, n is equal to the number of positions that can be substituted on Ar, and wherein each R, which may be the same or different, represents a hydrogen atom or a substituent selected from the group consisting of:
• group a, in which group a consists of:
• halogen atoms;
• hydroxyl;
• trifluoromethyl;
• linear and branched alkyl, alkenyl, alkynyl, and alkoxyl groups, all optionally further substituted by one or more of hydroxy groups, halogen atoms, alkoxy groups, amino groups, and alkylthio groups;
• linear and branched alkoxyl groups;
• linear and branched thioalkyl groups;
• aryl groups;
• aralkyl groups;
• aralkoxy groups;
• aryloxy groups;
• perfluoroalkyl;
• perfluoroalkoxy;
• —CN;
• the groups —NR4R5, —C(═X)NR4R5, —O—C(═X)NR4R5, —SO2NR4R5, or -Alk-NR4R5, in which X is oxygen or sulfur,
• Alk is an alkyl group, and
• R4 and R5 are the same or different and are H, alkyl, aralkyl, aryl, heteroaryl or heteroaralkyl and are optionally further substituted by one or more substituents selected from trifluoromethyl, halogen atoms and hydroxyl groups;
• the groups —NZC(═X)(NH)qR6, -Alk-NZC(═X)(NH)qR6, —C(═X)R6, or -Alk-C(═X)(NH)qR6,
• in which Z is H or C(═X)R6 wherein each X and each R6 is the same or different,
• q is 0 or 1 and, when q is 1, (NH)q is optionally substituted with a methyl, ethyl, or trifluoromethyl group,
• X is oxygen or sulfur,
• Alk is an alkyl group, and
• R6 is H, OH, alkyl, aralkyl, aryl, heteroaryl or heteroaralkyl and is optionally further substituted by one or more substituents selected from trifluoromethyl, halogen atoms and hydroxyl groups or,
• when C(═X) is CO, then C(═X)R6 may form an ester or thioester grouping;
• the groups —NHSO2R7, —SO2R7, —SOR7, or —SR7,
• in which R7 is OH or amino, or R7 is alkyl, aralkyl, alkylamino, aralkylamino, aryl, heteroaryl or heteroaralkyl, optionally further substituted by one or more substituents selected from trifluoromethyl, halogen atoms and hydroxyl groups;
• and saturated or 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;
• carboxyl;
• 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;
• alkoxycarbonylalkyl;
• perfluoroalkyl;
• perfluoroalkoxy;
• —CN;
• acyl;
• amino, alkylamino, dialkylamino, acylamino, and diacylamino groups;
• alkyl groups substituted with an amino, alkylamino, dialkylamino, acylamino, or diacylamino group;
• CONH2;
• alkylamido groups;
• alkylthio and the oxidised sulfoxide and sulfone forms thereof;
• sulfonyl, alkylsulfonyl groups;
• and sulfonamide, alkylsulfonamide, and di(alkylsulfonyl)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 when n is at least two, then two adjacent groups R may form a 5, 6, or 7 membered fused carbocyclic or heterocyclic ring with Ar, said fused ring being optionally further substituted with an oxo group or a substituent selected from group b as defined above,
• provided that, when p is 0, Ar is not thiazolyl or oxazolyl, either unfused or fused with a monocyclic aryl or a monocyclic heteroaryl in which the or any heteroatom is nitrogen,
• and salts and esters thereof.