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US 7,598,274 B2Granted
Pyrrole derivatives
AssigneeMerck Patent GmbH
InventorsDirk Finsinger, Hans-Peter Buchstaller, Lars Burgdorf, Matthias Wiesner, Christiane Amendt, Matthias Grell, Christian Sirrenberg, Frank Zenke
Life of this patent
Estimating the term…
Abstract
Compounds of the formula (I), in which X, Y, Z and Ar have the meanings indicated in claim 1, are inhibitors of Raf kinase and can be employed, inter alia, for the treatment of tumours
Claims24
A compound selected from:
- N-methyl-4-{4-[5-(4-chloro-3-trifluoromethylphenylcarbamoyl)-1H-pyrrol-3-yl]-phenoxy}pyridine-2-carboxamide,
- N-methyl-4-{3-[5-(4-chloro-3-trifluoromethylphenylcarbamoyl)-1H-pyrrol-3-yl]-phenoxy}pyridine-2-carboxamide,
- N-methyl-4-{4-[5-(3-chloro-4-methylphenylcarbamoyl)-1H-pyrrol-3-yl]phenoxy}-pyridine-2-carboxamide,
- N-methyl-4-{4-[5-(2-methoxy-5-trifluoromethylphenylcarbamoyl)-1H-pyrrol-3-yl]-phenoxy}pyridine-2-carboxamide,
- N-methyl-4-{3-[5-(3-chloro-4-methylphenylcarbamoyl)-1H-pyrrol-3-yl]phenoxy}-pyridine-2-carboxamide,
- N-methyl-4-{4-[5-(3-chloro-6-methoxyphenylcarbamoyl)-1H-pyrrol-3-yl]phenoxy}-pyridine-2-carboxamide,
- N-methyl-4-{3-[5-(3-chloro-6-methoxyphenylcarbamoyl)-1H-pyrrol-3-yl]phenoxy}-pyridine-2-carboxamide,
- N-methyl-4-{3-[5-(2-methoxy-5-trifluoromethylphenylcarbamoyl)-1H-pyrrol-3-yl]-phenoxy}pyridine-2-carboxamide,
- N-methyl-4-{3-[5-(2,5-dimethoxy-4-chlorophenylcarbamoyl)-1H-pyrrol-3-yl]-phenoxy}pyridine-2-carboxamide,
- N-methyl-4-{3-[5-(4-bromo-3-trifluoromethylphenylcarbamoyl)-1H-pyrrol-3-yl]-phenoxy}pyridine-2-carboxamide,
- N-methyl-4-{3-[5-(3-trifluoromethoxyphenylcarbamoyl)-1H-pyrrol-3-yl]phenoxy}-pyridine-2-carboxamide,
- N-methyl-4-{3-[5-(4-tert-butylphenylcarbamoyl)-1H-pyrrol-3-yl]phenoxy}pyridine-2-carboxamide,
- N-methyl-4-{3-[5-(3,4-dichlorophenylcarbamoyl)-1H-pyrrol-3-yl]phenoxy}pyridine-2-carboxamide,
- N-methyl-4-{3-[5-(4-chloro-3-methyl-6-methoxyphenylcarbamoyl)-1H-pyrrol-3-yl]-phenoxy}pyridine-2-carboxamide,
- N-methyl-4-{3-[5-(2,4-dimethoxy-5-trifluoromethoxyphenylcarbamoyl)-1H-pyrrol-3-yl]phenoxy}pyridine-2-carboxamide,
- N-methyl-4-{3-[5-(2-dimethylamino-5-trifluoromethylphenylcarbamoyl)-1H-pyrrol-3-yl]phenoxy}pyridine-2-carboxamide,
- N-methyl-4-{3-[5-(2-(2-methylaminoethoxy)-5-methylphenylcarbamoyl)-1H-pyrrol-3-yl]phenoxy}pyridine-2-carboxamide,
- N-methyl-4-{3-[5-(2-(2-dimethylaminoethoxy)-5-methylphenylcarbamoyl)-1H-pyrrol -3-yl]phenoxy}pyridine-2-carboxamide,
- N-methyl-4-{3-[5-(2-[(2-dimethylaminoethyl)methylamino]-5-methyl -phenylcarbamoyl)-1H-pyrrol-3-yl]phenoxy}pyridine-2-carboxamide,
- and pharmaceutically acceptable salts and stereoisomers thereof, including mixtures thereof in all ratios.
17 more elements
A process for the preparation of a compound according to 1, said process comprising:
- reacting a compound of formula II
- wherein L is Cl, Br, I or a free or reactively functionally modified OH group, X is O, and Ar is pyridinyl,
- with a compound of formula III
- Z-NH2 III
- wherein Z is 4-chloro-3-trifluoromethylphenyl, 3-chloro-4-methylphenyl, 2-methoxy-5-trifluoromethylphenyl, 3-chloro-6-methoxyphenyl, 2,5-dimethoxy-4-chlorophenyl, 4-bromo-3-trifluoromethylphenyl, 3-trifluoromethoxyphenyl, 4-tert-butylphenyl, 3,4-dichlorophenyl, 4-chloro-3-methyl-6-methoxyphenyl, 2,4-dimethoxy-5-trifluoromethoxyphenyl, 2-dimethylamino-5-trifluoromethylphenyl, 2-dimethylamino-5-trifluoromethylphenyl, 2-(2-methylaminoethoxy)-5-methylphenyl, 2-(2-dimethylaminoethoxy)-5-methyl, or 2-[(2-dimethylaminoethyl)methylamino]-5-methylphenyl,
- and, if the resultant compound is a base or acid, optionally converting said base or acid into a pharmaceutically acceptable salt thereof.
3 more elements
A compound of formula I-1
- wherein
- Ar is pyridinyl which is unsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by R1,
- X is —O—,
- R is H or A,
- R1 is A, Ar′, OR3, SR3, OAr′, SAr′, N(R3)2, NHAr′, Hal, NO2, CN, (CH2)mCOOR3, (CH2)mCON(R3)2, COR3, S(O)mA, S(O)mAr′, NHCOA, NHCOAr′, NHSO2A, NHSO2Ar′, or SO2N(R3)2,
- R3 is H, A or —(CH2)nAR′—,
- Ar′is phenyl which is unsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by A, Ph, OH, GA, SH, SA, OPh, SPh, NH2, NHA, NA2, NHPh, Hal, NO2, CN, (CH2)mCOOH, (CH2)mCOOA, (CH2)mCONH2, (CH2)mCONHA, CHO, COA, S(O)mA, S(O)mPh, NHCOA, NHCOPh, NHSO2A, NHSO2Ph, or SO2NH2,
- Ph is phenyl which is unsubstituted or mono-, di- or trisubstituted by A, Hal, CN, COOR, COOH, NH2, NO2, OH or OA,
- A is alkyl having 1 to 10 C atoms wherein 1-7 H atoms are each optionally replaced by F and/or chlorine,
- Hal is F,Cl, Br or I and
- m is 0, 1 or 2, or
- a salt, or stereoisomer thereof, including mixtures thereof in all ratios.
9 more elements
Dependencies are inferred from the claim text.