Novel pyrimidine derivatives, preparation thereof, and pharmaceutical use thereof as akt(pkb) phosphorylation inhibitors

10) Compounds of formula (Ib):

• wherein:
• Ab is a morpholine radical or a pyridyl radical, defined as follows:
• the morpholine radical, that Ab may represent, being substituted with one or more radicals selected from a deuterium atom, and alkyl radicals which are themselves optionally substituted with one or more radicals selected from halogen atoms and the hydroxyl radical, it being understood that two adjacent substituents of the morpholine can together form a cyclic radical with the carbon atoms to which they are bonded;
• the pyridyl radical, that Ab may represent, being optionally substituted with a halogen atom or an alkyl or alkoxy radical;
• R1b is an aryl or heteroaryl radical optionally substituted with one or more radicals, which may be identical or different, selected from halogen atoms and hydroxyl, CN, nitro, —COOH, —COOalk, —N(Rx)b, (Ry)b, —N(Rx)bCO(Ry)b, —CO(Ry)b, —N(Rx)bCO2(Rz)b, alkoxy, phenoxy, alkylthio, alkyl, alkenyl, alkynyl, cycloalkyl, O-cycloalkyl, heterocycloalkyl, aryl and heteroaryl radicals;
• the latter alkoxy, phenoxy, alkylthio, alkyl, alkenyl, alkynyl, heterocycloalkyl, aryl and heteroaryl radicals being themselves optionally substituted with one or more radicals, which may be identical or different, selected from halogen atoms and hydroxyl, alkoxy and N(Rv)b(Rw)b radicals;
• the aryl and heteroaryl radicals being, in addition, optionally substituted with one or more alkyl and alkoxy radicals which are themselves optionally substituted with one or more halogen atoms;
• it being possible for the heterocycloalkyl and heteroaryl radicals, in addition, to contain an oxo radical;
• Rb is a hydrogen atom or else forms, with R1b, a saturated or partially or totally unsaturated 5- or 6-membered ring fused to an aryl or heteroaryl residue and optionally containing one or more other heteroatoms selected from O, S, N, NH and Nalk, this bicyclic radical being optionally substituted with one or more radicals, which may be identical or different, selected from halogen atoms and hydroxyl, alkyl and alkoxy radicals;
• (Ra)b and (Rb)b, which may be identical or different, are independently a hydrogen atom, a halogen atom or an alkyl radical optionally substituted with one or more halogen atoms;
• (Rc)b is a hydrogen atom or an alkyl radical optionally substituted with one or more halogen atoms;
• N(Rx)b(Ry)b being such that (Rx)b is a hydrogen atom or an alkyl radical and (Ry)b is a hydrogen atom, a cycloalkyl radical or an alkyl radical optionally substituted with one or more radicals, which may be identical or different, selected from hydroxyl, alkoxy, N(Rv)b(Rw)b and heterocycloalkyl radicals;
• or (Rx)b and (Ry)b form, with the nitrogen atom to which they are bonded, a cyclic radical containing from 3 to 10 ring members and optionally one or more other heteroatoms selected from O, S, NH and N-alkyl, this cyclic radical being optionally substituted;
• N(Rv)b(Rw)b being such that (Rv)b is a hydrogen atom or an alkyl radical and (Rw)b is a hydrogen atom, a cycloalkyl radical or an alkyl radical optionally substituted with one or more radicals, which may be identical or different, selected from hydroxyl, alkoxy and heterocycloalkyl radicals;
• or (Rv)b and (Rw)b form, with the nitrogen atom to which they are bonded, a cyclic radical containing from 3 to 10 ring members and optionally one or more heteroatoms selected from O, S, NH and N-alkyl, this cyclic radical being optionally substituted;
• the cyclic radicals that (Rx)b and (Ry)b or (Rv)b and (Rw)b can respectively form with the nitrogen atom to which they are bonded, being optionally substituted with one or more radicals, which may be identical or different, selected from halogen atoms, and alkyl, hydroxyl, oxo, alkoxy, NH2, NHalk and N(alk)2 radicals;
• (Rz)b is the values for (Ry)b with the exception of hydrogen;
• (Rx)b, (Ry)b and (Rz)b in the N(Rx)bCO(Ry)b, —CO(Ry)b and N(Rx)bCO2(Rz)b radicals being selected from the meanings indicated above for (Rx)b, (Ry)b and (Rz)b;
• all the alkyl, alkoxy and alkylthio radicals above being linear or branched and containing from 1 to 6 carbon atoms,
• said compounds of formula (Ib) being in any of the possible racemic, enantiomeric and diastereoisomeric isomer forms, and also the addition salts with inorganic and organic acids or with inorganic and organic bases of said products of formula (Ib).

18) Compounds of formula (Ic):

• wherein:
• Rc is a hydrogen atom or an alkyl radical;
• R1c is a hydrogen atom or a methyl radical;
• R2c is a hydrogen atom or a fluorine atom;
• R3c is a hydrogen atom or a halogen atom;
• R4c is a hydrogen atom, a halogen atom or a hydroxyl, alkyl or alkoxy radical, the alkyl radicals being optionally substituted with one or more radicals, which may be identical or different, selected from halogen atoms and the hydroxyl radical, the alkoxy radicals being optionally substituted with one or more halogen atoms;
• R5c and R5′c, which may be identical or different, are a hydrogen atom or an alkyl radical or form, together with the carbon atom to which they are bonded, a cyclic radical containing from 3 to 7 ring members which is a spirocycloalkyl;
• R6c is a hydrogen atom or an alkyl radical optionally substituted with one or more radicals, which may be identical or different, selected from halogen atoms and hydroxyl and alkoxy radicals;
• said compounds of formula (Ic) being in any of the possible racemic, enantiomeric and diastereoisomeric isomer forms, and also the addition salts with inorganic and organic acids or with inorganic and organic bases of said compounds of formula (Ic).

26) Compounds of formula (Id):

• wherein:
• Rd is a hydrogen atom or an alkyl, cycloalkyl, aryl, heteroaryl, NH2 or CN radical;
• R1d is a hydrogen atom or a methyl radical;
• R2d is a hydrogen atom or a fluorine atom;
• R3d is a hydrogen atom or a halogen atom;
• R4d is a hydrogen atom, halogen atoms and hydroxyl, alkyl, alkoxy;
• heterocycloalkyl, aryl, heteroaryl and N(Rx)d(Ry)d radicals;
• all these alkyl, alkoxy, heterocycloalkyl, aryl and heteroaryl radicals being themselves optionally substituted with one or more radicals, which may be identical or different, selected from halogen atoms and hydroxyl, oxo, alkyl, heterocycloalkyl, alkoxy, N(Rv)d(Rw)d and —SO2Alk radicals;
• R5d and R5′d, which may be identical or different, are a hydrogen atom or an alkyl radical or form, together with the carbon atom to which they are bonded, a cyclic radical containing from 3 to 10 ring members optionally containing one or more heteroatoms selected from O, S and NH, these cyclic radicals being optionally substituted with one or more radicals, which may be identical or different, selected from halogen atoms and alkyl, cycloalkyl, hydroxyl, oxo, alkoxy, NH2, NHalk and N(alk)2 radicals;
• R6d is a hydrogen atom;
• an alkyl radical which is itself optionally substituted with one or more radicals, which may be identical or different, selected from halogen atoms, deuterium atoms and hydroxyl and alkoxy radicals;
• a cycloalkyl radical or a phenyl radical which is itself optionally substituted with one or more radicals, which may be identical or different, selected from halogen atoms or alkoxy radicals;
• it being possible for R5d and R6d to optionally form, with the carbon atoms to which they are bonded, a cyclic radical containing from 3 to 10 ring members optionally containing one or more heteroatoms selected from O, S and NH, these cyclic radicals being optionally substituted with one or more radicals, which may be identical or different, selected from halogen atoms and alkyl, hydroxyl, oxo, alkoxy, NH2, NHalk and N(alk)2 radicals;
• N(Rx)d(Ry)d being such that (Rx)d is a hydrogen atom or an alkyl radical and (Ry)d is a hydrogen atom, a cycloalkyl radical or an alkyl radical optionally substituted with one or more radicals, which may be identical or different, selected from hydroxyl, alkoxy, N(Rv)d(Rw)d and heterocycloalkyl radicals;
• or (Rx)d and (Ry)d form, with the nitrogen atom to which they are bonded, a cyclic radical containing from 3 to 10 ring members and optionally one or more other heteroatoms selected from O, S, NH and N-alkyl, this cyclic radical being optionally substituted with one or more radicals, which may be identical or different, selected from halogen atoms and hydroxyl, oxo, alkyl, heterocycloalkyl, alkoxy, N(Rv)d(Rw)d and —SO2Alk radicals;
• N(Rv)d(Rw)d being such that (Rv)d is a hydrogen atom or an alkyl radical and (Rw)d is a hydrogen atom, a cycloalkyl radical or an alkyl radical optionally substituted with one or more radicals, which may be identical or different, selected from hydroxyl, alkoxy and heterocycloalkyl radicals;
• or (Rv)d and (Rw)d form, with the nitrogen atom to which they are bonded, a cyclic radical containing from 3 to 10 ring members and optionally one or more other heteroatoms selected from O, S, NH and N-alkyl, this cyclic radical being optionally substituted with one or more radicals, which may be identical or different, selected from halogen atoms and hydroxyl, oxo, alkyl, heterocycloalkyl, alkoxy, NH2, NHalk, N(alk)2 and —SO2Alk radicals;
• said compounds of formula (Id) being in any of the possible racemic, enantiomeric and diastereoisomeric isomer forms, and also the addition salts with inorganic and organic acids or with inorganic and organic bases of said compounds of formula (Id).

35) Compounds of formula (Ie):

• wherein:
• Xe and Ye, which may be identical or different, are such that:
• Xe is O or S and Ye is S;
• Re is a hydrogen atom or an alkyl radical;
• R1e is a hydrogen atom or a methyl radical;
• R2e is a hydrogen atom or a fluorine atom;
• R3e is a hydrogen atom or a halogen atom;
• R4e is a hydrogen atom, a halogen atom or a hydroxyl, alkyl or alkoxy radical, the alkyl radicals being optionally substituted with one or more radicals, which may be identical or different, selected from halogen atoms and the hydroxyl radical, the alkoxy radicals being optionally substituted with one or more halogen atoms;
• R5e and R5′e, which may be identical or different, are a hydrogen atom or an alkyl radical;
• R6e is a hydrogen atom or an alkyl radical optionally substituted with one or more radicals, which may be identical or different, selected from halogen atoms and the hydroxyl radical;
• R7e is a hydrogen atom or a halogen atom;
• said compounds of formula (Ie) being in any of the possible racemic, enantiomeric and diastereoisomeric isomer forms, and also the addition salts with inorganic and organic acids or with inorganic and organic bases of said compounds of formula (Ie).