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US 8,410,143 B2Granted
Methylene urea derivatives
AssigneeMerck Patent GmbH
InventorsHans-Peter Buchstaller, Matthias Wiesner, Oliver Schadt, Christiane Amendt, Frank Zenke, Christian Sirrenberg, Matthias Grell, Dirk Finsinger
Life of this patent
Estimating the term…
Abstract
The present invention relates to methylene urea derivatives of formula (I), the use of the compounds of formula (I) as inhibitors of raf-kinase, the use of the compounds of formula (I) for the manufacture of a pharmaceutical composition and a method of treatment, comprising administering said pharmaceutical composition to a patient.
Claims5
A methylene urea compound selected from a compound of formula II,
- wherein
- Ar1 is pyridinyl,
- Ar2 is pyridinyl,
- R6, R7 are independently selected from the group consisting of H and A,
- E, G, M, Q and U are together with the carbon atom that E and U are bound to, a bivalent 6-membered aromatic ring which is phenylene;
- R8, R9 and R10 are independently selected from the group consisting of H, A, cycloalkyl having 3 to 7 carbon atoms, Hal, CH2Hal, CH(Hal)2, C(Hal)3, NO2, (CH2)nCN, (CH2)nNR11R12, (CH2)nO(CH2)kNR11R12, (CH2)nNR11(CH2)kNR11R12, (CH2)nO(CH2)kOR11, (CH2)nNR11(CH2)kOR12, (CH2)nCOOR13, (CH2)nCOR13, (CH2)nCONR11R12, (CH2)nNR11COR13, (CH2)nNR8CONR11R12, (CH2)nNR11SO2A, (CH2)nSO2NR11R12, (CH2)nS(O)uR13, (CH2)nOC(O)R13, (CH2)nCOR13, (CH2)nSR11, CH═N—OA, CH2CH═N—OA, (CH2)nNHOA, (CH2)nCH═N—R11, (CH2)nOC(O)NR11R12, (CH2)nNR11COOR13, (CH2)nN(R11)CH2CH2OR13, (CH2)nN(R11)CH2CH2OCF3, (CH2)nN(R11)C(R13)HCOOR8, (CH2)nN(R11), C(R13)HCOR8, (CH2)nN(R11)CH2CH2N(R12)CH2COOR8, (CH2)nN(R8)CH2CH2NR12R8, CH═CHCOOR13, CH═CHCH2NR11R12, CH═CHCH2NR11R12, CH═CHCH2OR13, (CH2)nN(COOR13)COOR14, (CH2)nN(CONH2)COOR13, (CH2)nN(CONH2)CONH2, (CH2)nN(CH2COOR13)COOR14, (CH2)nN(CH2CONH2)COOR13, (CH2)nN(CH2CONH2)CONH2, (CH2)nCHR13COR14, (CH2)nCHR13COOR14, (CH2)nCHR13CH2OR14, (CH2)nOCN and (CH2)nNCO, wherein
- R11, R12 are independently selected from the group consisting of H, A and (CH2)mAr3,
- R13, R14 are independently selected from the group consisting of H, Hal, A, (CH2)mAr4,
- A is selected from the group consisting of alkyl, alkenyl, cycloalkyl, alkylenecycloalkyl, alkoxy and alkoxyalkyl,
- Ar3, Ar4 are independently from one another aromatic hydrocarbon residues having 5 to 12 carbon atoms which are optionally substituted by one or more substituents, selected from the group consisting of A, Hal, NO2, CN, OR15, NR15R16, COOR15, CONR15R16, NR15COR16, NR15CONR15R16, NR16SO2A, COR15, SO2R15R16, S(O)uA and OOCR15,
- R15, R16 are independently selected from the group consisting of H, A, and (CH2)mAr6, wherein
- Ar6 is a 5- or 6-membered aromatic hydrocarbon which is optionally substituted by one or more substituents selected from the group consisting of methyl, ethyl, propyl, 2-propyl, tert.-butyl, Hal, CN, OH, NH2 and CF3,
- k, n and m are independently of one another 0, 1, 2, 3, 4, or 5;
- X O,
- Y is selected from O and S,
- p, r are independently from one another 0, 1, 2, 3, 4 or 5,
- q is 0, 1, 2, 3 or 4,
- u is 0, 1, 2 or 3,
- and
- Hal is independently selected from the group consisting of F, Cl, Br and I;
- or a pharmaceutically acceptable salt thereof.
18 more elements
The methylene urea compound according to claim 1, selected from the compounds of formula IIc, IIs and IIt,
- wherein R6, R7, R8, p, Ar1, Y, X, R9 and q are as defined in claim 3, R10 is H or as defined in claim 3,
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.