Claims for Patent: 7,511,041

Summary for Patent: 7,511,041

Title:	Fused azole-pyrimidine derivatives
Abstract:	The present invention relates to hovel fused azolepyrimidine derivatives, processes for preparing them and pharmaceutical preparations containing them. The fused azolepyrimidine derivatives of the present invention exhibit enhanced potency for phosphotidylinositol-3-kinase (PI3K) inhibition, especially for PI3K-γ inhibition and can be used for the prophylaxis and treatment of diseases associated with PI3K and particularly with PI3K-γ activity. More specifically, the azole derivatives of the present invention are useful for treatment and prophylaxis of diseases as follows: inflammatory and immunoregulatory disorders, such as asthma, atopic dermatitis, rhinitis, allergic diseases, chronic obstructive pulmonary disease (COPD), septic shock, joint diseases, autoixnmune pathologies such as rheumatoid arthritis, and Graves' disease, cancer, myocardial contractility disorders, heart failure, thromboembolism, ischemia, and atherosclerosis. The compounds of the present invention are also useful for pulmonary hypertension, renal failure, cardiac hypertrophy, as well as neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, diabetes and focal ischemia, since the diseases also relate to PI3K activity in a human or animal subject.
Inventor(s):	Mitsuyuki Shimada, Toshiki Murata, Kinji Fuchikami, Hideki Tsujishita, Naoki Omori, Issei Kato, Mami Miura, Klaus Urbahns, Florian Gantner, Kevin Bacon
Assignee:	Bayer AG, Bayer Intellectual Property GmbH
Application Number:	US10/527,376
Patent Claims:	1. A fused azolepyrimidine derivative of the formula (I), its tautomeric or stereoisomeric form, or a salt thereof: wherein X represents CR5R6 or NH; Y1 represents CR3 or N; Chemical bond between Y2═Y3 represents a single bond or double bond, with the proviso that when the Y2═Y3 represents a double bond, Y2 and Y3 independently represent CR4 or N, and when Y2═Y3 represents a single bond, Y2 and Y3 independently represent CR3R4 or NR4; Z1, Z2, Z3 and Z4 independently represent CH, CR2 or N; R1 represents aryl optionally having 1 to 3 substituents selected from R11, C3-8 cycloalkyl optionally having 1 to 3 substituents selected from R11, C1-6 alkyl optionally substituted by aryl, heteroaryl, C1-6 alkoxyaryl, aryloxy, heteroaryloxy or one or more halogen, C1-6 alkoxy optionally substituted by carboxy, aryl, heteroaryl, C1-6 alkoxyaryl, aryloxy, heteroaryloxy or one or more halogen, or a 3 to 15 membered mono- or bi-cyclic heterocyclic ring that is saturated or unsaturated, optionally having 1 to 3 substituents selected from R11, and contains 1 to 3 heteroatoms selected from the group consisting of N, O and S, wherein R11 represents halogen, nitro, hydroxy, cyano, carboxy, amino, N—(C1-6alkyl)amino, N-(hydroxyC1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N—(C1-6acyl)amino, N-(formyl)-N—(C1-6alkyl)amino, N—(C1-6alkanesulfonyl) amino, N-(carboxyC1-6-alkyl)-N—(C1-6alkyl)amino, N—(C1-6alkoxycabonyl)amino, N—[N,N-di(C1-6alkyl)amino methylene]amino, N—[N,N-di(C1-6alkyl)amino (C1-6alkyl)methylene]amino, N—[N,N-di(C1-6alkyl)amino C2-6alkenyl]amino, aminocarbonyl, N—(C1-6alkyl)aminocarbonyl, N,N-di(C1-6alkyl)aminocarbonyl, C3-8cycloalkyl, C1-6 alkylthio, C1-6alkanesulfonyl, sulfamoyl, C1-6alkoxycarbonyl, N-arylamino wherein said aryl moiety is optionally having 1 to 3 substituents selected from R101, N-(aryl C1-6alkyl)amino wherein said aryl moiety is optionally having 1 to 3 substituents selected from R101, aryl C1-6alkoxycarbonyl wherein said aryl moiety is optionally having 1 to 3 substituents selected from R101, C1-6alkyl optionally substituted by mono-, di- or tri-halogen, amino, N—(C1-6alkyl)amino or N,N-di(C1-6alkyl)amino, C1-6alkoxy optionally substituted by mono-, di- or tri-halogen, N—(C1-6alkyl)sulfonamide, or N-(aryl)sulfonamide, or a 5 to 7 membered saturated or unsaturated ring having 1 to 3 heteroatoms selected from the group consisting of O, S and N, and optionally having 1 to 3 substituents selected from R101 wherein R101 represents halogen, carboxy, amino, N—(C1-6 alkyl)amino, N,N-di(C1-6alkyl)amino, aminocarbonyl, N—(C1-6alkyl)aminocarbonyl, N,N-di(C1-6alkyl)aminocarbonyl, pyridyl, C1-6 alkyl optionally substituted by cyano or mono- di- or tri-halogen, and C1-6alkoxy optionally substituted by cyano, carboxy, amino, N—(C1-6alkyl)amino, N,N-di(C1-6alkyl)amino, aminocarbonyl, N—(C1-6alkyl)aminocarbonyl, N,N-di(C1-6alkyl)amino carbonyl or mono-, di- or tri-halogen; R2 represents hydroxy, halogen, nitro, cyano, amino, N—(C1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N-(hydroxyC1-6alkyl)amino, N-(hydroxyC1-6alkyl)-N—(C1-6alkyl)amino, C1-6 acyloxy, aminoC1-6 acyloxy, C2-6alkenyl, aryl, a 5-7 membered saturated or unsaturated heterocyclic ring having 1 to 3 heteroatoms selected from the group consisting O, S and N, and optionally substituted by hydroxy, C1-6 alkyl, C1-6 alkoxy, oxo, amino, amino C1-6alkyl, N—(C1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N—(C1-6 acyl)amino, N—(C1-6alkyl)carbonylamino, phenyl, phenyl C1-6 alkyl, carboxy, C1-6alkoxycarbonyl, aminocarbonyl, N-(C1-6alkyl)aminocarbonyl, or N,N-di(C1-6alkyl)amino, —C(O)—R20 wherein R20 represents C1-6 alkyl, C1-6 alkoxy, amino, N—(C1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N—(C1-6 acyl)amino, or a 5-7 membered saturated or unsaturated heterocyclic ring having 1 to 3 heteroatoms selected from the group consisting O, S and N, and optionally substituted by C1-6 alkyl, C1-6alkoxy, oxo, amino, N—(C1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N—(C1-6 acyl)amino, phenyl, or benzyl, C1-6 alkyl optionally substituted by R21, or C1-6 alkoxy optionally substituted by R21, wherein R21 represents cyano, mono-, di or tri-halogen, hydroxy, amino, N—(C1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N-(hydroxyC1-6 alkyl) amino, N-(halophenylC1-6 alkyl) amino, amino C2-6 alkylenyl, C1-6 alkoxy, hydroxyC1-6 alkoxy, —C(O)—R201, —NHC(O)—R201, C3-8cycloalkyl, isoindolino, phthalimidyl, 2-oxo-1,3-oxazolidinyl, aryl or a 5 or 6 membered saturated or unsaturated heterocyclic ring having 1 to 4 heteroatoms selected from the group consisting O, S and N, and optionally substituted by hydroxy, C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxycarbonyl, hydroxyC1-6 alkoxy, oxo, amino, aminoC1-6alkyl, N—(C1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N—(C1-6 acyl)amino, or benzyl, wherein R201 represents hydroxy, amino, N—(C1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N-(halophenylC1-6alkyl) amino, C1-6alkyl, aminoC1-6alkyl, aminoC2-6 alkylenyl, C1-6 alkoxy, a 5 or 6 membered saturated or unsaturated heterocyclic ring having 1 to 4 heteroatoms selected from the group consisting O, S and N, and optionally substituted by hydroxy, C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxycarbonyl, hydroxyC1-6 alkoxy, oxo, amino, N—(C1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N—(C1-6 acyl)amino or benzyl; R3 represents hydrogen, halogen, aminocarbonyl, or C1-6 alkyl optionally substituted by aryl C1-6 alkoxy or mono-, di- or tri-halogen; R4 represents hydrogen or C1-6 alkyl; R5 represents hydrogen or C1-6 alkyl; and R6 represents halogen, hydrogen or C1-6 alkyl. 2. The fused azolepyrimidine derivative of the formula (I), its tautomeric or stereoisomeric form, or a salt thereof as claimed in claim 1, wherein X represents CR5R6 or NH; Y1 represents N; Y2 and Y3 represent CR3R4; Chemical bond between Y2═Y3 represents a single bond; Z4 represents CH; Z1, Z2 and Z3 independently represent CH, CR2 or N; R1 represents C1-6 alkyl optionally substituted by mono-, di- or tri-halogen, phenyl, methoxyphenyl, phenoxy, or thienyl, C1-6 alkoxy optionally substituted by phenyl phenoxy, thienyl or mono-, di- or tri-halogen, or one of the following carbocyclic and heterocyclic rings selected from the group consisting of cyclopropyl, cyclopentyl, cyclohexyl, piperidinyl, piperazinyl, pyrrolyl, pyrazolyl, furyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, isoimidazolyl, pyrazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, phenyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1-benzothiophenyl, benzothiazolyl, benzimidazolyl, 3H-imidazo [4,5-b]pyridinyl, benzotriazolyl, indolyl, indazolyl, imidazo[1,2-a]pyridinyl, quino linyl, and 1,8-naphthyridinyl, wherein said carbocyclic and heterocyclic rings optionally substituted with 1 to 3 substituents selected from the group consisting of hydroxy, halogen, nitro, cyano, carboxy, amino, N—(C1-6alkyl)amino, N-(hydroxyC1-6alkyl)amino, N,N-di (C1-6alkyl)amino, N—(C1-6acyl)amino, N—(C1-6alkoxycarbonyl)amino, N-(formyl)-N—(C1-6alkyl)amino, N,N-di(C1-6alkyl) amino (C2-6alkenyl) amino, N—(C1-6alkane)sulfonyl amino, N[N,N-di(C1-6alkyl)amino methylene]amino, C1-6 alkylthio, C1-6alkanesulfonyl, sulfamoyl, C1-6alkoxy, C1-6alkoxycarbonyl, pyrrolyl, imidazolyl, pyrazolyl, pyrrolidinyl, pyridyl, phenyl C1-6alkoxycarbonyl, thiazolyl optionally substituted by pyridyl, piperazinyl optionally substituted by C1-6 alkyl or C1-6alkoxy and C1-6alkyl optionally substituted by mono-, di- or tri-halogen; R2 represents halogen, hydroxy, nitro, cyano, amino, N—(C1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N-(hydroxyC1-6alkyl)-N—(C1-6alkyl)amino, (C2-6)alkenyl, C1-6alkoxycarbonyl, aminocarbonyl, furyl, piperidino, morpholino, phenyl, pyrrolidinyl optionally substituted by N—(C1-6 acyl)amino, or N—(C1-6 alkyl)carbonylamino, piperidino optionally substituted by hydroxy, piperazinyl optionally substituted by C1-6alkyl, phenylC1-6alkyl, C1-6alkoxycarbonyl, or aminocarbonyl; C1-6 alkyl optionally substituted by amino, cyano, C1-6alkoxycarbonyl, morpholino, or mono-, di- or tri-halogen, or C1-6 alkoxy optionally substituted by hydroxy, cyano, carboxy, C1-6 alkoxy, C1-6 acyl, C1-6alkoxycarbonyl, amino, N—(C1-6alkyl)amino, N—(C1-6alkyl)aminocarbonyl, N,N-di(C1-6alkyl)amino, N,N-di(C1-6alkyl)aminocarbonyl, aminocarbonyl, aminoC1-6 alkylcarbonyl, N-(halobenzyl)aminocarbonyl, hydroxyC1-6 alkoxy, C3-6 cycloalkyl, morpholino, morpholinocarbonyl, pyrrolidinyl, pyrrolyl, piperidino, phthalimidyl, or piperazinyl optionally substituted by benzyl; R3 represents hydrogen; R4 represents hydrogen; R5 represents hydrogen; and R6 represents hydrogen. 3. The fused azolepyrimidine derivative of the formula (I), its tautomeric or stereoisomeric form, or a salt thereof as claimed in claim 1, wherein X represents CR5R6 or NH; Y1 represents N; Y2 and Y3 represent CR3R4; Chemical bond between Y2═Y3 represents a single bond Z4 represents CH; Z1, Z2 and Z3 independently represent N, CH CR2; R1 represents cyclopropyl, cyclopentyl, cyclohexyl, 2-furyl, 3-furyl, imidazolyl, pyrimidinyl, pyridazinyl, piperazinyl, 1,2,3-thiadiazolyl, 1,3-benzothiazolyl, quinolyl, 3H-imidazo[4,5-b]pyridinyl, 1H-pyrrol-2-yl optionally substituted by C1-6alkyl, 1H-pyrrol-3-yl optionally substituted by C1-6alkyl, pyrazolyl optionally substituted by 1 or 2 C1-6alkyl, isoxazolyl optionally substituted by 1 or 2 C1-6alkyl, 2-thienyl optionally substituted by chloro, nitro, cyano, or C1-6 alkyl, 3-thienyl optionally substituted by chloro, nitro, cyano, or C1-6 alkyl, piperidinyl optionally substituted by C1-6alkoxycarbonyl, or benzyloxycarbonyl, phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of fluoro, chloro, hydroxy, nitro, cyano, carboxy, C1-6 alkyl, C1-6alkoxy, C1-6alkoxycarbonyl, amino, N—(C1-6alkyl)amino, N—(C1-6acyl)amino, N—(C1-6alkoxycabonyl)amino, N,N-di(C1-6alkyl)amino, N-(formyl)-N—C1-6alkylamino, C1-6 alkylthio, C1-6alkanesulfonyl, sulfamoyl, pyrrolyl, imidazolyl, pyrazolyl, and piperazinyl optionally substituted by C1-6alkyl, pyridyl optionally substituted by 1 or 2 substituents selected from the group consisting of chloro, hydroxy, carboxy, C1-6alkoxy, C1-6alkylthio, amino, N—(C1-6alkyl)amino, N-(hydroxyC1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N—(C1-6acyl)amino, N—(C1-6alkane)sulfonyl amino, N[N,N-di(C1-6alkyl)amino methylene]amino, and C1-6alkyl optionally substituted by tri halogen, pyrazinyl optionally substituted by C1-6alkyl, 1,3-thiazolyl optionally substituted by 1 or 2 substituents selected from the group consisting of C1-6alkyl, pyridyl and N—(C1-6alkoxycrbonyl)amino, indolyl optionally substituted by C1-6alkyl, benzimidazolyl optionally substituted by C1-6alkyl or tri-halo C1-6alkyl, 1,2,3-benzotriazolyl optionally substituted by C1-6alkyl, 1,8-naphthyridinyl optionally substituted by C1-6alkyl optionally substituted by tri halogen, C1-6 alkyl optionally substituted by tri-halogen, phenyl, phenoxy, or thienyl, or C1-6alkoxy optionally substituted by phenyl, phenoxy, or thienyl; R2 represents fluoro, chloro, bromo, hydroxy, nitro, vinyl, cyano, amino, aminoacetoxy, N—(C1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N-(hydroxyC1-6alkyl)-N—(C1-6alkyl)amino, 2-furyl, piperidino, morpholino, phenyl, pyrrolidinyl optionally substituted by acetamido, piperidino optionally substituted by hydroxy, piperazinyl optionally substituted by methyl, benzyl, C1-6 alkoxycarbonyl, or aminocarbonyl, C1-6 alkyl optionally substituted by cyano, tri-fluoro, carboxy, methoxycarbonyl, aminocarbonyl, tert-butoxycarbonyl, tetrahydropyranyl, or morpholino, C1-6 alkoxy optionally substituted by hydroxy, cyano, methoxy, methoxycarbonyl, tert-butoxycarbonyl, carboxy, aminoacetyl, dimethylamino, aminocarbonyl, methylaminocarbonyl, dimethylamino carbonyl, isopropylaminocarbonyl, fluorobenzylaminocarbonyl, cyclopropyl, pyrrolidinyl, piperidino, tetrahydropyranyl, morpholino, morpholinocarbonyl, 2-oxo-1,3-oxazolidin-4-yl, phthalimid-N-yl, or hydroxy C1-6 alkyleneoxy, R3 represents hydrogen; R4 represents hydrogen; R5 represents hydrogen; and R6 represents hydrogen. 4. The fused azolepyrimidine derivative of the formula (I), its tautomeric or stereoisomeric form, or a salt thereof as claimed in claim 1, wherein X represents CR5R6 or NH; Y1 represents N; Y2 and Y3 represent CR3R4; Chemical bond between Y2═Y3 represents a single bond; Z3 and Z4 represent CH; Z1 and Z2 independently represent CH or CR2; R1 represents cyclopropyl, cyclopentyl, cyclohexyl, 2-furyl, 3-furyl, imidazolyl, 1H-pyrrol-2-yl, 1H-pyrrol-3-yl, pyrimidinyl, pyridazinyl, piperazinyl, 1,2,3-thiadiazolyl, 1,3-benzothiazolyl, quinolyl, 3H-imidazo [4,5-b]pyridinyl, pyrrolyl optionally substituted by C1-6alkyl, pyrazolyl optionally substituted by 1 or 2 C1-6alkyl, isoxazolyl optionally substituted by 1 or 2 C1-6alkyl, 2-thienyl optionally substituted by chioro, nitro, cyano, or C1-6 alkyl, 3-thienyl optionally substituted by chloro, nitro, cyano, or C1-6 alkyl, piperidinyl optionally substituted by C1-6alkoxycarbonyl, or benzyloxycarbonyl, phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of fluoro, chloro, hydroxy, nitro, cyano, carboxy, C1-6 alkyl, C1-6alkoxy, C1-6alkoxycarbonyl, amino, N—(C1-6alkyl)amino, N—(C1-6acyl)amino, N—(C1-6alkoxycabonyl)amino, N,N-di(C1-6alkyl)amino, N-(formyl)-N—C1-6alkylamino, C1-6 alkylthio, C1-6alkanesulfonyl, sulfamoyl, pyrrolyl, imidazolyl, pyrazolyl, and piperazinyl optionally substituted by C1-6alkyl, pyridyl optionally substituted by 1 or 2 substituents selected from the group consisting of chloro, hydroxy, carboxy, C1-6alkoxy, C1-6alkylthio, amino, N—(C1-6alkyl)amino, N-(hydroxyC1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N—(C1-6acyl)amino, N—(C1-6alkane)sulfonyl amino, N[N,N-di(C1-6alkyl)amino methylene]amino, and C1-6alkyl optionally substituted by tri halogen, pyrazinyl optionally substituted by C1-6alkyl, 1,3-thiazolyl optionally substituted by 1 or 2 substituents selected from the group consisting of C1-6alkyl, pyridyl and N—(C1-6alkoxycrbonyl)amino, indolyl optionally substituted by C1-6alkyl, benzimidazolyl optionally substituted by C1-6alkyl or tri-halo C1-6alkyl, 1,2,3-benzotriazolyl optionally substituted by C1-6alkyl, 1,8-naphthyridinyl optionally substituted by C1-6alkyl optionally substituted by tri halogen, C1-6 alkyl optionally substituted by tri-halogen, phenyl, phenoxy, or thienyl, or C1-6alkoxy substituted by phenyl, phenoxy, or thienyl; R2 represents fluoro, chioro, bromo, hydroxy, nitro, vinyl, cyano, amino, aminoacetoxy, N—(C1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N-(hydroxyC1-6alkyl)-N—(C1-6alkyl)amino, 2-furyl, piperidino, morpho lino, phenyl, pyrrolidinyl optionally substituted by acetamido, piperidino optionally substituted by hydroxy, piperazinyl optionally substituted by methyl, benzyl, C1-6alkoxycarbonyl, or aminocarbonyl, C1-6 alkyl optionally substituted by cyano tri-fluoro, carboxy, methoxycarbonyl, aminocarbonyl, tert-butoxycarbonyl, tetrahydropyranyl, or morpholino, or C1-6 alkoxy optionally substituted by hydroxy, cyano, methoxy, methoxycarbonyl, tert-butoxycarbonyl, carboxy, aminoacetyl, dimethylamino, aminocarbonyl, methylaminocarbonyl, dimethylamino carbonyl, isopropylamino carbonyl, fluorobenzylaminocarbonyl, cyclopropyl, pyrrolidinyl, piperidino, tetrahydropyranyl, morpholino, morpholinocarbonyl, 2-oxo- 1,3-oxazolidin-4-yl, phthalimid-N-yl, or hydroxy C1-6 alkyleneoxy; R3 represents hydrogen; R4 represents hydrogen; R5 represents hydrogen; and R6 represents hydrogen. 5. The fused azolepyrimidine derivative of the formula (I), its tautomeric or stereoisomeric form, or a salt thereof as claimed in claim 1, wherein X represents CR5R6 or NH; Y1 represents N; Y2 and Y3 represent CR3R4; Chemical bond between Y2═Y3 represents a single bond; Z1 and Z4 represent CH; Z2 and Z3 independently represent CH or CR2; R1 represents cyclopropyl, cyclopentyl, cyclohexyl, 2-furyl, 3-furyl, imidazolyl, 1H-pyrrol-2-yl, 1H-pyrrol-3-yl, pyrimidinyl, piperazinyl, pyridazinyl, 1,2,3-thiadiazolyl, 1,3-benzothiazolyl, quinolyl, 3H-imidazo [4,5-b]pyridinyl, pyrrolyl optionally substituted by C1-6alkyl, pyrazolyl optionally substituted by 1 or 2 C1-6alkyl, isoxazolyl optionally substituted by 1 or 2 C1-6alkyl, 2-thienyl optionally substituted by chloro, nitro, cyano, or C1-6 alkyl, 3-thienyl optionally substituted by chloro, nitro, cyano, or C1-6 alkyl, piperidinyl optionally substituted by C1-6alkoxycarbonyl, or benzyloxycarbonyl, phenyl optionally substituted by 1 to 3 substituents selected from the group consisting of fluoro, chloro, hydroxy, nitro, cyano, carboxy, C1-6 alkyl, C1-6alkoxy, C1-6alkoxycarbonyl, amino, N—(C1-6alkyl)amino, N—(C1-6acyl)amino, N—(C1-6alkoxycabonyl)amino, N,N-di(C1-6alkyl)amino, N-(formyl)-N—C1-6alkyl-amino, C1-6 alkylthio, C1-6alkanesulfonyl, sulfamoyl, pyrrolyl, imidazolyl, pyrazolyl, and piperazinyl optionally substituted by C1-6alkyl, pyridyl optionally substituted by 1 or 2 substituents selected from the group consisting of chloro, hydroxy, carboxy, C1-6alkoxy, C1-6alkylthio, amino, N—(C1-6alkyl)amino, N-(hydroxyC1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N—(C1-6acyl)amino, N—(C1-6alkane)sulfonyl amino, N[N,N-di(C1-6alkyl)amino-methylene]amino, C1-6alkoxyphenylC1-6alkoxy, and C1-6alkyl optionally substituted by tri halogen, pyrazinyl optionally substituted by C1-6alkyl, 1,3-thiazolyl optionally substituted by 1 or 2 substituents selected from the group consisting of C1-6alkyl, pyridyl and N—(C1-6alkoxycrbonyl)amino, indolyl optionally substituted by C1-6alkyl, benzimidazolyl optionally substituted by C1-6alkyl or tri-halo C1-6alkyl, 1,2,3-benzotriazolyl optionally substituted by C1-6alkyl, 1,8-naphthyridinyl optionally substituted by C1-6alkyl optionally substituted by tri halogen, C1-6 alkyl optionally substituted by tri-halogen, phenyl, phenoxy, or thienyl, or C1-6alkoxy substituted by phenyl, phenoxy, or thienyl; R2 represents fluoro, chloro, bromo, hydroxy, nitro, vinyl, cyano, amino, aminoacetoxy, N—(C1-6alkyl)amino, N,N-di(C1-6alkyl)amino, N-(hydroxyC1-6alkyl)-N—(C1-6alkyl)amino, 2-furyl, piperidino, morpho lino, phenyl, pyrrolidinyl optionally substituted by acetamido, piperidino optionally substituted by hydroxy, piperazinyl optionally substituted by methyl, benzyl, C1-6alkoxycarbonyl, or aminocarbonyl, C1-6 alkyl optionally substituted by cyano, tri-fluoro, carboxy, methoxycarbonyl, aminocarbonyl, tert-butoxycarbonyl, tetrahydropyranyl, or morpholino, or C1-6 alkoxy optionally substituted by hydroxy, cyano, methoxy, methoxycarbonyl, tert-butoxycarbonyl, carboxy, aminoacetyl, dimethylamino, aminocarbonyl, methylaminocarbonyl, dimethylamino carbonyl, isopropylamino carbonyl, fluorobenzylamino carbonyl, cyclopropyl, pyrrolidinyl, piperidino, tetrahydropyranyl, morpho lino, morpho linocarbonyl, tetrazolyl, 2-oxo-1,3-oxazolidin-4yl, phthalimid-N-yl, or hydroxy C1-6 alkyleneoxy; R3 represents hydrogen; R4 represents hydrogen; R5 represents hydrogen; and R6 represents hydrogen. 6. The fused azolepyrimidine derivative of the formula (I), its tautomeric or stereoisomeric form, or a salt thereof as claimed in claim 1, X represents CR5R6 or NH; Y1 represents N; Y2 and Y3 represent CR3R4; Chemical bond between Y2═Y3 represents a single bond; Z3 and Z4 represent CH; Z1 and Z2 independently represent CH or CR2; R1 represents 3H-imidazo [4,5-b]pyridinyl, benzimidazolyl pyridyl optionally substituted by hydroxy, amino, acetamido, methoxybenzyloxy or methylsulfonylamino, or 1,3-thiazolyl optionally substituted by 1 or 2 methyl; R2 represents fluoro, chloro, bromo, morpholino, piperazinyl, methylpiperazinyl, methyl, tri-fluoro methyl, or C1-6 alkoxy optionally substituted by hydroxy, cyano, carboxy, dimethylaminocarbonyl, tetrahydropyranyl, morpholino, morpholinocarbonyl, tetrazolyl, or phthalimid-N-yl; R3 represents hydrogen; R4 represents hydrogen; R5 represents hydrogen; and R6 represents hydrogen. 7. The fused azolepyrimidine derivative of the formula (I), its tautomeric or stereoisomeric form, or a salt thereof as claimed in claim 1, X represents CR5R6 or NH; Y1 represents N; Y2 and Y3 represent CR3R4; Chemical bond between Y2═Y3 represents a single bond; Z1, Z3 and Z4 represent CH; Z2 represents CR2; R1 represents 3H-imidazo [4,5-b]pyridinyl, benzimidazolyl pyridyl optionally substituted by hydroxy, amino, acetamido, methoxybenzyloxy or methylsulfonylamino, or 1,3-thiazolyl optionally substituted by 1 or 2 methyl, R2 represents fluoro, chloro, bromo, morpholino, piperazinyl, methylpiperazinyl, methyl, tri-fluoro methyl, C1-6 alkoxy optionally substituted by hydroxy, cyano, carboxy, dimethylaminocarbonyl, tetrahydropyranyl, morpholino, morpholinocarbonyl, tetrazolyl, or phthalimid-N-yl; R3 represents hydrogen; R4 represents hydrogen; R5 represents hydrogen; and R6 represents hydrogen. 8. The fused azolepyrimidine derivative of the formula (I), its tautomeric or stereoisomeric form, or a salt thereof as claimed in claim 1, wherein said derivative is selected from the group consisting of the following compounds: N-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide; 2-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1-pyridin-3-ylethyleno; N-(7,8-dimethoxy-2,3-dihydroimidazol[1,2-c]quinazolin-5-yl)-1H-benzimidazole-5-carboxamide; 6-(acetamido)-N-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide; N-{5-[2-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1-hydroxyvinyl]pyridin-2-yl}acetamide; 2-({5-[2-hydroxy-2-pyridin-3-ylvinyl]-7-methoxy-2,3-dihydroimidazo[1,2-]quinazolin-8-yl}oxy)-N,N-dimethylacetamide; 2-[7-methoxy-8-(tetrahydro-2H-pyran-2-ylmethoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]-1-pyridin-3-ylethylenol; 2-[8-(2-hydroxyethoxy)-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]-1-pyridin-3-ylethylenol1; ({5-[2-hydroxy-2-pyridin-3-ylvinyl]-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-yl}oxy)acetic acid; 4-({5-[2-hydroxy-2-pyridin-3-ylvinyl]-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-yl}oxy)butanoic acid; ({5-[2-hydroxy-2-pyridin-3-ylvinyl]-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-yl}oxy)acetonitrile; 2-[7-methoxy-8-(2H-tetrazol-5-ylmethoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]-1-pyridin-3-ylethyleno1; 2-[7-methoxy-8-(4-morpholin-4-yl-4-oxobutoxy)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]-1-pyridin-3-ylethylenol; 5-[1-hydroxy-2-(8-morpholin-4-yl-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)vinyl]pyridin-3-ol; N-(2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-5-hydroxynicotinamide; 6-(acetamido)-N-(7,9-dimethoxy-8-methyl-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide; N-(8,9-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-5-hydroxynicotinamide; 5-hydroxy-N-(7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide; N-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-5-[(4-methoxybenzyl)oxy]nicotinamide; N-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-5-hydroxynicotinamide; 5-hydroxy-N-[8-(trifluoromethyl)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]nicotinamide; N-{8-[3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)propoxy]-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl}nicotinamide; N-(7-bromo-8-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide; 6-amino-N-(8-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide; 1-(1H-benzimidazol-5-yl)-2-(8,9-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)ethylenol; 2-(8,9-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1-(2,4-dimethyl-1,3-thiazol1-5-yl)ethylenol; N-(9-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-l H-benzimidazole-5-carboxamide; N-(8-bromo-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide; N-(8-bromo-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1H-benzimidazole-5-carboxamide; N-(8-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1H-benzimidazole-5-carboxamide; N-(8-methyl-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1H-benzimidazole-5-carboxamide; N-[8-(trifluoromethyl)-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl]-1H-benzimidazole-5-carboxamide; N-(7-fluoro-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1H-benzimidazole-5-carboxamide; N-(7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide; N-(8-chloro-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-1H-benzimidazole-5-carboxamide; 6-(acetamido)-N-(8-morpholin-4-yl-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)nicotinamide; 1-(1H-benzimidazol-5-yl)-2-(8-morpholin-4-yl-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)ethylenol; N-{5-[1-hydroxy-2-(8-morpholin-4-yl-2,3-dihydroimidazol[1,2-c]quinazolin-5-yl)vinyl]pyridin-2-yl}acetamide; 6-methyl-N-(8-morpholin-4-y-2,3-dihydroimidazol[1,2-c]quinazolin-5-yl)nicotinamide; 1-(1H-benzimidazol-5-yl)-2-[8-(4-methylpiperazin-1-yl)-2,3-dihydroimidazol[1,2-c]quinazolin-5-yl]ethylenol; N-(2,3-dihydroimidazol[1,2-c]quinazolin-5-yl)-3H-imidazo[4,5-b]pyridine-6-carboxamide; N-(7,8-dimethoxy-2,3-dihydroimidazol[1,2-c]quinazolin-5-yl)-3H-imidazo[4,5-b]pyridine-6-carboxamide; N-[7-(trifluoromethyl)-2,3-dihydroimidazol[1,2-c]quinazolin-5-yl]-1H-benzimidazole-5-carboxamide; N-(7,9-dimethoxy-2,3-dihydroimidazol[1,2-c]quinazolin-5-yl)-1H-benzimidazole-5-carboxamide; N-{5-[2-(7,9-dimethoxy-8-methyl-2,3-dihydroimidazol[1,2-c]quinazolin-5-yl)-1-hydroxyvinyl]pyridin-2-yl}acetamide; N-{5-[2-(7-bromo-9-methyl-2,3-dihydroimidazol[1,2-c]quinazolin-5-yl)-1-hydroxyvinyl]pyridin-2-yl}acetamide; and 2-(8,9-dimethoxy-2,3-dihydroimidazol[1,2-c]quinazolin-5-yl)-1-pyridin-3-ylethylenol. 9. A medicament comprising the fused azolepyrimidine derivative, its tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof as claimed in claim 1 as an active ingredient. 10. The medicament as claimed in claim 9, further comprising one or more pharmaceutically acceptable excipients. 11. The medicament as claimed in claim 9, wherein the fused azolepyrimidine derivative, its tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof is a PI3K inhibitor. 12. The medicament as claimed in claim 9, wherein the fused azolepyrimidine derivative, its tautomeric or stereoisomeric form, or a physiologically acceptable salt thereof is a PI3K-γ inhibitor.