FIELD: organic chemistry, medicine, oncology, pharmacy.
SUBSTANCE: invention relates to novel compounds of the general formula: A-D-B (I) given in the invention description, or their pharmaceutically acceptable salts that possess property of raf kinase inhibitors and can be used in treatment of disease associated with growth of cancer cells mediated by effect of this kinase. In compounds of the general formula A-D-B (I) D value is represented by the formula -NH-C(O)-NH-; A means a substituted structure comprising up to 40 carbon atoms of the formula -L-(M-L1)q wherein L represents pyridyl or phenyl substituted with halogen atom or (C1-C4)-alkyl, or 6-membered nitrogen-containing heterocyclic structure bound with D directly; L1 comprises possibly substituted (C5-C7)-aryl or (C5-C8)-nitrogen-containing heterocyclic group; M is a bridge group comprising at least one atom chosen from -O-, -S-, -CO-NH-, -NH-CO-; q is a whole number = 1 or 2; B represents substituted or unsubstituted (C6-C14)-aryl group or 6-membered heteroaryl group comprising 1-4 heteroatoms chosen from nitrogen, oxygen and sulfur atoms, and wherein L1 is substituted with at least one substitute chosen from group consisting of -SO2Rx, -C(O)Rx and -C(NRy)Rz, and if L1 means phenyl then -SO2Rx can not represent -SO3H; Ry means (C1-C4)-alkoxy group; Rz means hydroxy group, (C1-C4)-alkyl or (C1-C4)-alkoxy group; Rx means Rz or NRaRb wherein Ra and Rb: (a) are represented by hydrogen atom, (C1-C)-alkyl group substituted possibly hydroxy group, (C1-C4)-alkoxy group or (C5-C6)-heterocyclic group comprising 1-2 heteroatoms chosen from nitrogen (N) and oxygen (O) atoms that can be substituted with (C1-C4)-alkyl or amino group substituted possibly with (C1-C4)-alkyl group, or phenyl, or -OSi(Rf)3 wherein Rf means (C1-C4)-alkyl group; phenyl substituted possibly with halogen atom, amino group that can be substituted with (C1-C4)-alkyl groups, or (C4-C6)-heterocyclic group comprising 1-2 heteroatoms chosen from N and O that can be substituted with pyridyl; pyridyl substituted possibly with (C1-C4)-alkoxy group; or (b) Ra and Rb form in common 5-7-membered heterocyclic nitrogen-containing group substituted with phenyl that can be substituted with (C1-C4)-alkylcarbonyl, pyridyl or halogen atom; if B represents a substituted residue then substitutes are chosen from group consisting of halogen atom and Wn wherein n = 1-3, and each W is chosen from group consisting of (C1-C4)-alkyl substituted possibly with halogen atom up to perhalogen; (C1-C4)-alkyl substituted with halogen atom up to perhalogen; phenoxy group substituted with mono-(C1-C4)-alkylamino group in phenyl ring; 5-6-membered nitrogen-containing heteroaryl group substituted with (C1-C4)-alkyl groups, and L1 can be substituted additionally with one substitute chosen from group consisting of (C1-C4)-alkyl and (C1-C4)-alkoxy group. Also, invention relates to a pharmaceutical composition and to a method for treatment of diseases.
EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.
66 cl, 7 tbl, 103 ex
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