Thiazole compounds and their pharmaceutical use

A compound of formula (I)

• wherein Nu is a heterocyclic nucleus selected from thiazole in which the R1, R2 and R3 substituents are disposed as indicated below
• wherein
• R1 is pyrimidyl or pyridyl;
• X is —NR6—Y—, —O— or —S—;
• where
• R6 is H,
• C1-C4alkyl, C3-C8cycloalkyl, C3-C8cycloalkylC1-C3alkyl, C6-C18aryl, C3-C18heteroaryl, C7-C19aralkyl or C4-C19heteroaralkyl, and —Y— is C1-C4alkylene or a direct bond;
• R2 is phenyl, optionally substituted by one or more substituents, each of which is independently selected from
• Halo,
• CF3,
• Cyano,
• amido or thioamido, which is optionally mono- or di-N-substituted by C1-C4alkyl or the N atom of which forms a 5- to 7-membered heterocyclic ring optionally having an additional hetero atom selected from O, S or N, which N is optionally C1-C4alkyl C1-C4alkylcarbonyl or C1-C4alkylthiocarbonyl substituted;
• carboxylate or thiocarboxylate,
• optionally in the form of an optionally halo-substituted C1-C10alkoxy, C2-C10alkenoxy, C2-C10alkynoxy, C3-C7cyclalkoxy, C5-C7cycloalkenoxy, aryloxy, arylalkoxy, heteroaryloxy or heteroarylalkoxy ester,
• optionally mono- or di-C1-C4alkyl-substituted-C0-C1alkyl optionally C1-C4alkyl- or C3-C5cycloalkyl-substituted-carbonyl or -thiocarbonyl,
• optionally halo-substituted-C1-C4alkoxy, C2-C4alkenoxy, C2-C4alkynoxy, C3-C5cycloalkoxy or C3-C5cyclothioalkoxy,
• optionally halo substituted C1-C4alkyl;
• oxycarbonyl or optionally N—C1-C4alkyl-substituted aminocarbonyl both of which are optionally C1-C4alkyl or C3-C5cycloalkyl substituted,
• optionally mono- or di-C1-C4alkyl-substituted-C0-C1alkylamine which is optionally mono- or di-N—C1-C4alkyl substituted,
• optionally mono- or di-C1-C4alkyl-substituted-C0-C1alkyl optionally N—C1-C4alkyl-substituted amino-carbonyl or -thiocarbonyl,
• optionally N—C1-C4alkyl-substituted amino-sulphinyl or -sulphonyl optionally substituted by
• optionally mono- or di-N—C1-C4alkyl-substituted amino,
• a nitrogen atom which forms a heterocyclic ring of 5 to 7 members optionally having an additional heteroatom selected from O, S or N, which N is optionally C1-C4alkyl C1-C4alkylcarbonyl or C1-C4alkylthiocarbonyl substituted;
• or
• sulphinyl or sulphonyl optionally substituted by
• optionally halo-substituted-C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl,
• optionally mono- or di-C1-C4alkyl-substituted amino,
• a nitrogen atom which form a heterocyclic ring of 5 to 7 members optionally having an additional heteroatom selected from O, S or N, which N is optionally C1-C4alkyl C1-C4alkylcarbonyl or C1-C4alkylthiocarbonyl substituted;
• R3 is H, amino, C1-C10alkyl, C3-C10cycloalkyl, C3-C18heterocycloalkyl, C6-C18aryl, or C3-C18heteroaryl each of which is optionally substituted by up to 4 substituents separately selected from C1-C4alkyl, halogen, halo-substitued-C1-C4alkyl, hydroxy, C1-C4alkoxy, C1-C4alkylthio, C6-C18aryl, C3-C18heteroaryl, C6-C18arylC1-C4alkyl, C3-C18heteroarylC1-C4alkyl, C3-C18heterocycloalkyl or optionally mono- or di-C1-C4alkyl substituted amino or by N-heterocyclyl having from 5- to 7-ring atoms and optionally a further hetero atom selected from O, S or N, all of which are further optionally substituted halo, hydroxy, C1-C4alkyl, C1-C4alkoxy or C1-C4alkoxycarbonyl;
• and
• R4 is C1-C10alkyl, C6-C18aryl, C3-C18heteroaryl, or C3-C12cycloalkyl optionally substituted by up to 3 substituents separately selected from C1-C4alkyl, halogen, halo-substitued-C1-C4alkyl, hydroxy, C1-C4alkoxy, C1-C4alkylthio, optionally mono- or di-C1-C4alkyl substituted amino, or by N-heterocyclyl having from 5- to 7-ring atoms and optionally having a further hetero atom selected from O, S or N;
• or pharmaceutically-acceptable esters thereof, or acid addition salts thereof, or, when said compound comprises one or more free hydroxyl groups, the pharmaceutically-acceptable prodrug esters thereof, which are cleavable under physiological conditions to release the compound having one or more free hydroxyl groups.