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US 8,557,813 B2Granted
2-benzylpyridazinone derivatives as met kinase inhibitors
AssigneeMerck Patent GmbH
InventorsDieter Dorsch, Oliver Schadt, Frank Stieber, Andree Blaukat
Life of this patent
Estimating the term…
Abstract
Compounds of the formula I in which R1, R2, R3, R4′ have the meanings indicated in claim 1, are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumors.
Claims15
A compound of formula I
- in which
- R1 denotes H or A,
- R2 denotes an unsaturated, saturated or aromatic 5- or 6-membered heterocycle having 1 to 4 N, O and/or S atoms, which is unsubstituted or mono-, di- or trisubstituted by Hal, A, [C(R3)2]nOR3, N═CR3N(R3)2, SR3, NO2, CN, COOR3, CON(R3)2, NR3COA, NR3SO2A, SO2N(R3)2, S(O)mA, [C(R3)2]nN(R3)2, [C(R3)2]nHet, O[C(R3)2]nN(R3)2, O[C(R3)2]nHet, S[C(R3)2]nN(R3)2, S[C(R3)2]nHet, NR3[C(R3)2]nN(R3)2, NR3[C(R3)2]nHet, NHCON(R3)2, NHCONH[C(R3)2]nN(R3)2, NHCONH[C(R3)2]nHet, [C(R3)2]nNHCO[C(R3)2]nN(R3)2, [C(R3)2]nNHCO[C(R3)2]nHet, CON(R3)2, CONR3[C(R3)2]nN(R3)2, CONR3[C(R3)2]nNR3COOA, CONR3[C(R3)2]nOR3, CONR3[C(R3)2]nHet, COHet, COA and/or ═O,
- R3 denotes H or A,
- R4, R4′ each, independently of one another, denote H, Hal, A, OR3, CN, COOR3, CON(R3)2, NR3COA, NR3SO2A, SO2N(R3)2 or S(O)mA,
- Ar denotes phenyl, naphthyl or biphenyl, which is unsubstituted or mono-, di- or trisubstituted by Hal, A, [C(R3)2]nOR3, [C(R3)2]nN(R3)2, SR3, NO2, CN, COOR3, CON(R3)2, NR3COA, NR3SO2A, SO2N(R3)2, S(O)mA, CO-Het, Het, O[C(R3)2]n—N(R3)2, O[C(R3)2]nHet, NHCOOA, NHCON(R3)2, NHCOO[C(R3)2]nN(R3)2, NHCOO[C(R3)2]nHet, NHCONH[C(R3)2]nN(R3)2, NHCONH[C(R3)2]nHet, OCONH[C(R3)2]1N(R3)2, OCONH[C(R3)2]nHet, CONR3[C(R3)2]nN(R3)2, CONR3[C(R3)2]nHet and/or COA,
- Het denotes a mono-, bi- or tricyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N, O and/or S atoms, which is unsubstituted or mono-, di- or trisubstituted by Hal, A, [C(R3)2]nOR3, [C(R3)2]nN(R3)2, SR3, NO2, CN, COORS, CON(R3)2, NR3COA, NR3SO2A, SO2N(R3)2, S(O)mA, CO-Het1, [C(R3)2]nHet1, O[C(R3)2]nN(R3)2, O[C(R3)2]nHet1, NHCOOA, NHCON(R3)2, NHCOO[C(R3)2]nN(R3)2, NHCOO[C(R3)2]nHet1, NHCONH[C(R3)2]nN(R3)2, NHCONH[C(R3)2]nHet1, OCONH[C(R3)2]nN(R3)2, OCONH[C(R3)2]nHet1, CO-Het1, CHO, COA, ═S, ═NH, ═NA and/or ═O,
- Het1 denotes a monocyclic saturated heterocycle having 1 to 2 N and/or O atoms, which is unsubstituted or mono- or disubstituted by A, OA, OH, Hal and/or ═O,
- A denotes unbranched or branched alkyl having 1-10 C atoms, in which 1-7 H atoms are optionally replaced by F and/or in which one or two non-adjacent CH2 groups are optionally replaced by O, NH, S, SO, SO2 and/or by CH═CH groups,
- or
- cyclic alkyl having 3-7 C atoms,
- Hal denotes F, Cl, Br or I,
- m denotes 0, 1 or 2, and
- n denotes 0, 1, 2, 3 or 4,
- or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof.
12 more elements
A compound, which is one of the following compounds
- No.
- Name and/or structure
- “A1”
- 2-[3-(5-Bromopyrimidin-2-yl)benzyl]-6-cyclopropyl-2H-
- pyridazin-3-one
- “A2”
- 6-Cyclopropyl-2-(3-{5-[1-(2-pyrrolidin-1-ylethyl)-1H-pyrazol-4-
- yl]pyrimidin-2-yl}benzyl)-2H-pyridazin-3-one
- “A3”
- 6-Cyclopropyl-2-(3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-
- yl]pyrimidin-2-yl}benzyl)-2H-pyridazin-3-one
- “A4”
- 6-Cyclopropyl-2-[3-(5-methylpyrimidin-2-yl)benzyl]-2H-
- pyridazin-3-one
- “A5”
- 6-Cyclopropyl-2-{3-[5-(1-piperidin-4-yl-1H-pyrazol-4-yl)-
- pyrimidin-2-yl]benzyl}-2H-pyridazin-3-one
- “A6”
- 6-Methyl-2-{3-[5-(1-piperidin-4-yl-1H-pyrazol-4-yl)pyrimidin-2-
- yl]benzyl}-2H-pyridazin-3-one
- “A7”
- 6-Cyclopropyl-2-[3-(5-methyl-1,2,4-oxadiazol-3-yl)benzyl]-2H-
- pyridazin-3-one
- “A8”
- 6-Cyclopropyl-2-{3-[5-(3-dimethylaminopropoxy)pyrimidin-2-
- yl]-benzyl}-2H-pyridazin-3-one
- “A9”
- 6-Cyclopropyl-2-{3-[5-(1-methylpiperidin-4-yloxy)pyrimidin-2-
- yl]benzyl}-2H-pyridazin-3-one
- “A10”
- 2-{3-[5-(3-Dimethylaminopropoxy)pyrimidin-2-yl]benzyl}-6-
- isopropyl-2H-pyridazin-3-one
- “A11”
- 6-Cyclopropyl-2-{3-[5-(piperidin-4-yloxy)pyrimidin-2-
- yl]benzyl}-2H-pyridazin-3-one
- “A12”
- 6-Cyclopropyl-2-{3-[5-(4-methylpiperazin-1-yl)pyrimidin-2-yl]-
- benzyl}-2H-pyridazin-3-one
- “A13”
- 6-Isopropyl-2-(3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-
- yl]-pyrimidin-2-yl}benzyl)-2H-pyridazin-3-one
- “A14”
- 2-(3-{5-[1-(2-Morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-
- 2-yl}benzyl)-2H-pyridazin-3-one
- “A15”
- 6-Cyclobutyl-2-(3-{5-[1-(2-pyrrolidin-1-ylethyl)-1H-pyrazol-4-
- yl]-pyrimidin-2-yl}benzyl)-2H-pyridazin-3-one
- “A16”
- 6-Cyclobutyl-2-{3-[5-(3-dimethylaminopropoxy)pyrimidin-2-yl]-
- benzyl}-2H-pyridazin-3-one
- “A17”
- 6-Cyclopropyl-2-{3-[5-(2-morpholin-4-ylethoxy)pyrimidin-2-yl]-
- benzyl}-2H-pyridazin-3-one
- “A18”
- 2-[3-(5-Aminopyrimidin-2-yl)benzyl]-6-cyclopropyl-2H-
- pyridazin-3-one
- or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof.
54 more elements
Dependencies are inferred from the claim text.