Dihidropirazolonas substituted with Heterocyclic Compounds, Preparation Method, Medicine containing them and uses in prophylaxis and / or treatment of cardiovascular, hematologic and renal.

摘要

Claim 1: 81) compound of formula wherein R1 represents a heteroaryl Group of formulas (2) where * means the connection Point of the Ring of dihidropirazolona, appearance means in each individual C - or n R4, representing a maximum of two members of the same tie Ring MPO, and e means o, s or N - R5,R2 represents a heteroaryl Group of formulas (3) which means the connection Point of the Ring of dihidropirazolona, g in each individual appearance means c or N - R6, representing a maximum of two members of G Ring at the same time n, J is o, s or N - R7, and l in each appearance I Ndividual R8 means C - or n, representing a maximum of two members of the Ring at the same time,The R4, R6, R8 are the same or different and represent in each case individually, independently of each other, hydrogen or a Substituent selected from the group of halogeno, cyano, Nitro alkyl, cycloalkyl C1 - C3 - 6, 7, heterocicloalquilo 4 to 10 members, phenyl heteroaryl, 5 or 6. Bros, - C (= o) - R9, - C (= o) - or10, - C (= o) - nr11r12, - or - C (= o) - R13, - or - C (= o) nr14r15 nr16 -, - C (= o) - R17- NR18 - C (= o) - or19 nr20 -, - C (= o) - nr21r22 - SO2 -, - nr23 R24, R25 - SO2 -, nr26r27 or28 - SO2 -, -, - and - nr30r31 sr29, in which (i) alkyl C1 - 6 may be replaced by its part one to three times, so the same or different, with remains of selected Group of halogeno, cyano, Oxo, cycloalkyl C3 - 7, heter Ocicloalquilo 4 to 10 members, phenyl heteroaryl of 5 or 6 members, - C (= o) - R9, - C (= o) - or10,- C (= o) - nr11r12, - or - C (= o) - R13, - or - C (= o) nr14r15 nr16 -, - C (= o) - R17 NR18 -, - C (= o) - or19 nr20 -, - C (= o) - nr21r22, - nr23 - SO2 - R24, R25 - SO2 -, nr26r27 or28 - SO2 -, -, - and - nr30r31 sr29, which remains heterocicloalquilo cycloalkyl, phenyl heteroaryl cited, and finally can be replaced in turn re Spectivamente three times to form the same or different, halogeno, cyano, c1-4 alkyl,Trifluoromethyl c1-4 alkoxy, Hydroxy, amino, trifluoromethoxy, Oxo, monoalquil C1 - 4 - amino - 4 - C1, dialkyl amino hidroxicarbonilo and / or c1-4 alkoxy carbonyl, (ii) heterocicloalquilo cycloalkyl C3 - 7, 4 to 10 members, and heteroaryl phenyl 5 or 6 members can be replaced in turn respect Selectively from one to three times, so the same or different.With remains selected 6 alkyl group C1, halogeno, cyano, Oxo, - C (= o) - R9, - C (= o) - or10, - C (= o) - nr11r12, - or - C (= o) - R13, - or - C (= o) nr14r15 nr16 -, - C (= o) - R17 NR18 -, - C (= o) - or19 nr20 -, - C (= o) - nr21r22 - SO2 -, - nr23 R24, R25 - SO2 -, nr26r27 or28 - SO2 -, -, - and - nr30r31 sr29, in which the aryl cited Rest Finally can be again replaced up to three times, so the same or different.With halogeno, cyano, Hydroxy, trifluoromethoxy, c1-4 alkoxy, amino - 4 - amino monoalquil C1, C1 - C4 - dialkyl amino hidroxicarbonilo, c1-4 alkoxy carbonyl, heterocicloalquilo cycloalkyl C3 - 7, 4 to 7 members, and / or heteroaryl phenyl 5 or 6 members (III R9, R10, R11), R13, R14, R17, R19, R21, R2 4, R25, R26, R28,R29, R30 represent independently in each selected individual appearance a rest Group C1 - 6 Hydrogen, alkyl, cycloalkyl heterocicloalquilo C3 - 7, 4 to 10 members, and heteroaryl phenyl 5 or 6 members, in which heterocicloalquilo cycloalkyl C3 - 7, 4 to 10 Wed E,Heteroaryl phenyl 5 and 6 may be replaced in turn respectively to three times of the same or different, halogeno, cyano, trifluoromethyl, c1-4 alkyl, Hydroxy, c1-4 alkoxy, amino, monoalquil trifluoromethoxy, Oxo, C1 - 4 - amino - 4 - C1, dialkyl amino hidroxicarbonilo and / or C1-4 alkoxy alkyl and carbonyl, C1 - 6 can be replaced once to three times,Of the same or different, halogeno, cyano, Hydroxy, trifluoromethoxy, c1-4 alkoxy, amino, monoalquil C1 - 4 - amino - 4 - C1, dialkyl amino hidroxicarbonilo, c1-4 alkoxy carbonyl, heterocicloalquilo cycloalkyl C3 - 7, 4 to 7, 5 and / or heteroaryl phenyl (iv) or 6 members, R12, R15 and R16, r 18, R20, R23, R22,R27 and R31 is independently at each occurrence of a selected individual rest of hydrogen and alkyl group C1 - 6, in which alkyl C1 - 6 can be replaced once to three times, so the same or different, halogeno, cyano, Hydroxy, trifluoromethoxy, c1-4 alkoxy, Amin Or, monoalquil C1 - 4 - amino - 4 - C1, dialkyl amino hidroxicarbonilo and / or c1-4 alkoxy carbonyl,And / or (V) The R11 and R12, R14 and R15 and R16, R17 and R18 and R19, R20 R21, R22 and R23 and R21, R24, R26, R27, R30, R31 and may form pairs, respectively, together with those Atoms that are United, a heterocicloalquilo Ring of 5 or 6 members that can be substituted to a Three times in the same or different, halogeno, cyano, trifluoromethyl, c1-4 alkyl, Hydroxy,C1-4 alkoxy, amino, monoalquil trifluoromethoxy, Oxo, C1 - 4 - amino - 4 - C1, dialkyl amino hidroxicarbonilo and / or c1-4 alkoxy carbonyl, and R5, R7 are identical or different and are independently Hydrogen or a Substituent selected from the group of 6 C1 - C3 alkyl, cycloalkyl heter - 7 Ocicloalquilo 4 to 7 members, and heteroaryl phenyl 5 or 6 members.In which (i) alkyl C1 - 6 may be replaced by its part one to three times, so the same or different, with remains of selected Group of halogeno, cyano, Oxo, cycloalkyl heterocicloalquilo C3 - 7, 4 to 7 members, phenyl heteroaryl of 5 or 6 members, - C (R9 = o) -, - C (= o) - or10, - C (= o) Nr11r12 -, - or - C (= o) - R13, - or - C (= o) nr14r15 nr16 -, - C (= o) - R17 NR18 -, - C (= o) - or19 nr20 -, - C (= o) - nr21r22,- nr23 - SO2 - R24, R25 - SO2 -, nr26r27 or28 - SO2 -, -, - and - nr30r31 sr29, which remains heterocicloalquilo cycloalkyl, phenyl heteroaryl cited, and finally can be replaced in turn respectively to three times of the same or different with Halogen, alkyl, cyano, c1-4, trifluoro Methyl, Hydroxy, c1-4 alkoxy, amino, monoalquil trifluoromethoxy, Oxo, C1 - 4 - aminoDialkyl C1 - 4 - amino hidroxicarbonilo and / or c1-4 alkoxy carbonyl, and (ii) heterocicloalquilo cycloalkyl C3 - 7, 4 to 7 members and heteroaryl phenyl 5 or 6 members can be replaced in turn respectively, one to three times, so the same or different, with remains selected Grup Or alkyl of C1 - 6, halogeno, cyano, Oxo, - C (= o) - R9, - C (= o) - or10, - C (= o) - nr11r12, - or - C (= o) - R13,- or - C (= o) nr14r15 nr16 -, - C (= o) - R17 NR18 -, - C (= o) - or19 nr20 -, - C (= o) - nr21r22 - SO2 -, - nr23 R24, R25 - SO2 -, nr26r27 or28 - SO2 -, -, - - nr30r31 sr29 and rent the rest, which finally can be cited again replaced up to three times, so the same or different, with Halogen.Ciano, Hydroxy, trifluoromethoxy, c1-4 alkoxy, amino, monoalquil C1 - 4 - amino - 4 - C1, dialkyl amino hidroxicarbonilo, c1-4 alkoxy carbonyl, heterocicloalquilo cycloalkyl C3 - 7, 4 to 7 members, and / or heteroaryl phenyl 5 or 6 members, in which (to R9, R10, R11), R13, R14, R17, R19, R21, R24, R2 5, R26, R28,R29, R30 represent independently in each selected individual appearance a rest Group C1 - 6 Hydrogen, alkyl, cycloalkyl heterocicloalquilo C3 - 7, 4 to 7 members and heteroaryl phenyl 5 or 6 members, in which heterocicloalquilo cycloalkyl C3 - 7, 4 to 7. Bros,Heteroaryl phenyl 5 or 6 members can be replaced in turn respectively to three times of the same or different, halogeno, cyano, trifluoromethyl, c1-4 alkyl, Hydroxy, c1-4 alkoxy, amino, monoalquil trifluoromethoxy, Oxo, C1 - 4 - amino - 4 - C1, dialkyl amino hidroxicarbonilo and C1-4 alkoxy or alkyl and carbonyl, C1 - 6 can be replaced once to three times,Of the same or different, halogeno, cyano, Hydroxy, trifluoromethoxy, c1-4 alkoxy, amino, monoalquil C1 - 4 - amino - 4 - C1, dialkyl amino hidroxicarbonilo, c1-4 alkoxy carbonyl, heterocicloalquilo cycloalkyl C3 - 7, 4 to 7, 5 and / or heteroaryl phenyl (b) or 6 members, R12, R15 and R16, R1 8, R20, R23, R22,R27 and R31 is independently at each occurrence of a selected individual rest of hydrogen and alkyl group C1 - 6, in which alkyl C1 - 6 can be replaced once to three times, so the same or different, halogeno, cyano, Hydroxy, trifluoromethoxy, c1-4 alkoxy, Ami No, monoalquil C1 - 4 - amino - 4 - C1, dialkyl amino hidroxicarbonilo and / or c1-4 alkoxy carbonyl,And / or (c) R11 and R12, R14 and R15 and R16, R17 and R18 and R19, R20 R21, R22 and R23 and R21, R24, R26, R27, R30, R31 and may form pairs, respectively, together with those Atoms that are United, a ring heterocicloalquilo 5 or 6 members that can be substituted for one to three times, Of the same or different, halogeno, cyano, trifluoromethyl, c1-4 alkyl, Hydroxy, alkoxy c1-4,Trifluoromethoxy, Oxo, amino, monoalquil C1 - 4 - amino - 4 - C1, dialkyl amino hidroxicarbonilo and / or c1-4 alkoxy carbonyl and R3 represents Hydrogen, alkyl, cycloalkyl C1 - C3 - 6 or 7, as well as their salts, solvates and solvates of salts, with the exception of the compounds: 3 - Methyl - 1 - (pyridin-2-yl) - 4 - (1 - RIP Idin - il - 2 - 3 - methyl) - 1H pyrazole - 5 - (ii) - 2H - pirazolin - 3 - 5 - (1H) - One, 3, 5 - dimethyl - 2 - phenyl - 2 - (4 '- phenyl - 13 - thiazol-2-yl) - 1 h, 2H bipirazol 3,4 '- 5' - ol, 3 ', 5 - dimethyl - 2 - phenyl - 1' - (thiophen-2-yl - 1.3 - thiazol-2-yl) - 1 h, 2H - 3.4 bipirazol '- 5' - ol, 3 ', 5' - dimethyl - 1 - (4 - methyl - 1.3 - thiazol-2-yl) - phenyl - 2 - 1 h, 2H bipirazol 3,4 '- 5' - ol, 2 - (4-chlorophenyl) - 3 ', 5' - dimethyl - 2 - (4 '- phenyl - 1.3 - thiazol-2-yl) - 1 h, 2H bipirazol 3,4' - 5 '- ol, and Tert Butyl 2 - (1 '- [4 - (4-chlorophenyl) - 1,3 - thiazole - 2 - II] - 3', 5 '- dimethyl - 1 h, 2H bipirazol 3,4' - 5 '- ol.