5-Phenylthiazole derivatives and their use as p13 kinase inhibitors

A compound of formula I

• in free or salt form, wherein
• R1 is a 5 or 6-membered heterocyclic ring containing nitrogen and optionally one or more further hetero atoms selected from the group consisting of nitrogen, oxygen and sulphur, that ring being optionally substituted by halo, C1-C8-alkyl optionally substituted by —NR6R7, carboxy, C1-C8-alkoxycarbonyl or a 5 or 6-membered heterocyclic ring containing at least one hetero atom selected from the group consisting of nitrogen, oxygen and sulphur, C1-C8-alkoxy, —NR6R7, C3-C8-cycloalkyl optionally substituted by carboxy, or a 5 or 6-membered heterocyclic ring containing at least one hetero atom selected from the group consisting of nitrogen and oxygen, that ring being optionally substituted by C1-C8-alkyl;
• R2 is C1-C8-alkyl or halo;
• R3 is hydroxy, halo, C1-C8-alkoxy, C1-C8-alkylcarbonyl, —SO2NR8R9, —SOR10 or —SO2R11, carboxy, aminocarbonyl, di(C1-C8-alkyl)aminocarbonyl, —NO2 or cyano and is in the para or meta position with respect to the indicated thiazole ring;
• R4 and R5 are each independently hydrogen, C1-C8-alkyl, C1-C8-alkoxy optionally substituted by a 5 or 6-membered heterocyclic ring containing at least one hetero atom selected from the group consisting of nitrogen, oxygen and sulphur, halo, halo-C1-C8-alkyl, cyano, —SO2NH2, carboxy, amino, amino-C1-C8-alkyl, di(C1-C8-alkyl)amino-C1-C8-alkyl, amino-C1-C8-alkoxy, di(C1-C8-alkyl)amino-C1-C8-alkoxy, aminocarbonyl, C1-C8-alkylaminocarbonyl, di(C1-C8-alkyl)aminocarbonyl, —NR2R3, carboxy-C1-C8-alkyl, carboxy-C1-C8-alkoxy, R14, —OR14 or a 5 or 6-membered heterocyclic ring containing at least one hetero atom selected from the group consisting of nitrogen, oxygen and sulphur, that ring being optionally substituted by C1-C8-alkyl;
• R6 is hydrogen or C1-C8-alkyl;
• R7 is C1-C8-alkyl optionally substituted by hydroxy, C1-C8-alkoxy, di(C1-C8-alkyl)amino or a 5 or 6-membered heterocyclic ring containing at least one hetero atom selected from the group consisting of nitrogen, oxygen and sulphur, that ring being optionally substituted by C1-C8-alkyl;
• R8 is hydrogen or C1-C8-alkyl optionally substituted by hydroxy, C1-C8-alkoxy, cyano, amino, C1-C8-alkylamino, di(C1-C8-alkyl)amino or a 5 or 6-membered heterocyclic ring having one or more ring hetero atoms selected from the group consisting of oxygen, nitrogen and sulphur, that ring being optionally substituted by C1-C8-alkyl;
• R9 is hydrogen, C1-C8-alkyl optionally substituted by hydroxy, or C3-C8-cycloalkyl;
• R10 is C1-C8-alkyl;
• R11 is C1-C8-alkyl optionally substituted by halogen, hydroxy, C1-C8-alkoxy, cyano, amino, C1-C8-alkylamino or di(C1-C8-alkyl)amino;
• R12 is hydrogen or C1-C8-alkyl;
• R13 is C1-C8-alkyl or C3-C8-cycloalkyl optionally substituted by hydroxy, amino,
• C1-C8-alkylamino or di(C1-C8-alkyl)amino or R12 and R13 together with the nitrogen atom to which they are attached form a 5 or 6-membered saturated or unsaturated heterocyclic ring that contains one or more further hetero atoms selected from the group consisting of oxygen, nitrogen and sulphur, that ring being optionally substituted by C1-C8-alkyl;
• and
• R14 is C1-C8-alkyl optionally substituted by hydroxy or —NR2R13.