Bicyclic Heterocycles, their physiologically compatible salts, Medications that contain procedures for Preparation and use of these to prepare an appropriate medication for the treatment of certain diseases such as tumor, Kidney and skin.

摘要

Describes bicyclic Heterocycles of General formula (1), in which ra is a hydrogen Atom or a c1-4 alkyl group, RB means a benzyl or phenyl Group, feniletilo 1 -, in which the core is replaced in each case with phenyl Radicals R1 to R3, where R1 and R2, PU Eden be equal or different, each represent an atom of hydrogen, Fluorine, Chlorine,Bromine or Iodine, a c1-4 alkyl group, Hydroxy, alkoxy 4 C1 - C3, C4 cicloalcoxi cycloalkyl - 6, - 6, - 5 alquinilo alquenilo C2 or C2 - 5, an aryl Group, or ariloxi, arilmetilo arilmetoxi, a Group alqueniloxi c3-5 or alquiniloxi c3-5, could not be the unsaturated part linked with the Oxygen Atom. A c1-4 alkyl group sulfenilo C1 -, alkyl - 4sulfinilo c1-4 alkyl sulfonyl trifluorometilsulfenilo -,,Trifluorometilsulfinilo or trifluorometilsulfonilo, a Methyl or methoxy Group substituted with 1 to 3 Fluorine ATOMS, a substituted ethoxy Ethyl group or with 1 to 5 Atoms of Fluorine Group, a cyano or Nitro or amino Group eventually replaced with one or two c1-4 alkyl groups, May be its Tituyentes EQUAL or different, R1 and R2, if they are connected to adjacent carbon Atoms.Mean a Group - ch = CH - ch = CH - ch = CH - ch = N or - NH - NH and R3 represents an atom of hydrogen, Fluorine, Chlorine or Bromine, a c1-4 alkyl group, or trifluormetilo c1-4 alkoxy, RC and Rd, which may be identical or different. In each case an Atom of hydrogen, Fluorine or chlorine, a methoxy group or a Methyl Group substituted with a methoxy Group eventually, dimethylamino, Diethylamino, pirrolidino,Piperidino or morpholino, X means a methine Group substituted with a cyano group or a nitrogen Atom, an oxygen Atom, a Means or an imino Group eventually replaced with a c1-4 alkyl group, a carbonyl or sulfonyl Group B means C means a Group alenileno 1.1 - 1.3 -, or 1.2 - vinyleneIn each case can be replaced with one or two Methyl group or a trifluoromethyl Group, a group or a Group etinileno butadien - 1.3 - 1.4 - full eventually substituted with 1 to 4 Methyl groups or a trifluoromethyl Group, D means a group alquileno, co alquileno or alquileno - SO2 -, In the part of alquileno contains in each case 1 to 8 Carbon Atoms and, Additionally,1 to 4 Atoms of hydrogen in the part of alquileno can be replaced by Fluorine ATOMS, and made the Link Group Co alquileno and - SO2 - alquileno with Group c in each case through the adjacent carbonyl group or sulfonyl Group, a co - or - alquileno, co - NR4 alquileno or - S Alquileno NR4 - O2 -, in which the part of alquileno contains in each case 1 to 8 Carbon Atoms.The Link must be contiguous with Group c in each case through the carbonyl or sulfonyl Group, in the R4 represents a hydrogen Atom or a c1-4 alkyl group, or, in the case that d is attached to a carbon atom of the radical and also means a link or in the Case That is attached to a nitrogen atom of the radical and,It also means a carbonyl or sulfonyl Group, e means a Group r6o co Rent - NR5 (r7o po 0R8 (NR5) - Rent - or r7o - R9) - Rent - NR5, where in each case the part of alquileno, which is a linear chain and contains 1 to 6 carbon ATOMS, can also be replaced with a Or two alkyl groups C1 - 2 or a Group r6o co or co r6o c1-2 alkyl,Wherein R5 represents a hydrogen Atom, an alkyl group C1 - 4, which can be substituted with a Group r6o co, (r7o 0R8 (PO) or r7o - R9), a group Ethyl or propyl eventually replaced with one or two Methyl or Ethyl Group, which in each case terminal position is substituted with a group Alkyl carbonilsulfenilo cicloalquil C1 - C3 - 6 - 7 -, carbonyl - sulfenilo,Cicloalquil C1 - C3 - 7 - 3 - carbonilsulfenilo alkyl, aryl or alkyl sulfenilo arilcarbonil - C1 - 3 - carbonilsulfenilo, an Ethyl or propyl Group eventually replaced with one or two Methyl or Ethyl groups, in each case at Terminal position is substituted with an alkyl group C1 - 6 - carbonyloxy, cicloalqui L - 7 - cicloalquil carbonyloxy C3, C1 - C3 - 7 - 3 - alkyl carbonyloxy,Arilcarboniloxi or arilalquil C1 - 3 - carbonyloxy, an Ethyl or propyl Group eventually replaced with one or two Methyl or Ethyl groups, each position is substituted with a Terminal Hydroxy Group, c1-4 alkoxy, amino, c1-4 alkyl amino - or di - (c1-4 alkyl) amino - - or rent a group Imino 4 to 7 members,Where alquilenimino in groups of 6 to 7 members mentioned above, in each case, a methylene Group in position 4 can be replaced by an oxygen or Sulphur Atom, by a group sulfinilo, sulfonyl, OR N - (imino imino c1-4 alkyl) - a cycloalkyl Group, C3 or cicloalquil C3 - 7 7 C1-3 alkyl, R6, R7 and R8, which may be the same or differentEach represent a hydrogen Atom, an alkyl group C1 - 8 can be substituted with a hydroxyl Group, c1-4 alkoxy, amino, c1-4 alkyl amino - or di - (c1-4 alkyl) amino -, or with a Group alquilenimino 4 to 7 members, where the groups of 6 to 7 members precedenteme alquilenimino Nte mentioned,In each case a methylene Group in position 4 can be replaced by an oxygen or Sulphur Atom, by a group sulfinilo, sulfonyl, OR N - (imino c1-4 alkyl) - imino Group, a Hydroxy, alkoxy c1-4 alkyl, amino, c1-4 alkyl amino - or di - (C1 - 4 - amino - or with a Group of 4 to 7 alquilenimino Member S,Where alquilenimino in groups of 6 to 7 members mentioned above, in each case, a methylene Group in position 4 can be replaced by an oxygen or Sulphur Atom, by a group sulfinilo, sulfonyl, OR N - (imino imino c1-4 alkyl) - a cycloalkyl Group, C3 or cicloalquil C3 - 7 7 C1-3 alkyl, R6, R7 and R8, which may be the same or differentEach represent a hydrogen Atom, an alkyl group C1 - 8 can be substituted with a hydroxyl Group, c1-4 alkoxy, amino, c1-4 alkyl amino - or di - (c1-4 alkyl) amino -, or with a Group alquilenimino 4 to 7 members, where the groups of 6 to 7 members precedenteme alquilenimino Nte mentioned,In each case a methylene Group in position 4 can be replaced by an oxygen or Sulphur Atom, by a group sulfinilo, sulfonyl, OR N - (imino imino c1-4 alkyl) -, a cycloalkyl Group C4 - 7 eventually replaced with 1 or 2 Methyl groups, a group alquenilo - 5 or alquinilo C3 C3 - 5, Not pudien Do the unsaturated part to be linked with the Oxygen Atom, a Group cicloalquil 7alquilo C1 - C3 - 4Aryl or arylalkyl C1 -, 4 - or rGCo (recrf), where re and RF, which may be identical or different, each represent a hydrogen Atom or a c1-4 alkyl group, R represents an alkyl group C1 - C3 - 7 4, cycloalkyl, c1-4 alkoxy or cicloalcoxi C5 - 7, and R9 represents a c1-4 alkyl group, Ari Arylalkyl or C1 - 4A group of 4 to 7 alquilenimino Member is replaced with a Group r6o co, (r7o 0R8 (PO), r7o - R9), co r6o c1-4 alkyl -, bis - (CO r6o c1-4 alkyl) -, (r7o po 0R8) - c1-4 alkyl (or r7o - R9) c1-4 alkyl, the R6 to R9 are defined as mentioned above, a group of alq Uilenimino 4 to 7 members is replaced with two groups r6o co or co r6o c1-4 alkyl,Or with a Group r6o co and a Group r6o co c1-4 alkyl, the R6 is defined as mentioned above, a Group piperazino or homopiperazino, in position 4 is replaced with the radical R10 and, Additionally, is replaced by a carbon atom of the Ring R with a group 6th - CO, (r7o 0R8 (PO), r7o - R9), co r6o c1-4 alkyl -, bis - (CO r6o c1-4 alkyl) -,(r7o po 0R8 c1-4 alkyl) - or (r7o - R9) c1-4 alkyl, which are defined as R6 to R9 and R10 was mentioned above, represents a hydrogen Atom, an alkyl group Formilo c1-4 alkyl, C1 -, 4 - or carbonyl c1-4 alkyl Sulfonyl -, a Group piperazino or homopiperazino, in position Radical ion 4 is replaced with the R10Additionally, carbon Atoms in the ring is replaced with two groups r6o co or co r6o c1-4 alkyl, or with a Group r6o co and CO - - a Group r6o c1-4 alkyl R6 and R10, which are defined as mentioned above, a Group piperazino or homopiperazino, which in each case and N 4 position is replaced as a Group r6o co c1-4 alkyl -, bis - (CO r6o c1-4 alkyl) -,(r7o po 0R8 c1-4 alkyl) - or (r7o - R9) c1-4 alkyl, and additionally in the Ring carbon Atoms is replaced with one or two groups r6o co or co r6o c1-4 alkyl, or with a Group r6o co and a Group Co r6o c1-4 alkyl, the R6 to R9 are defined as mentioned precedentement And a Group homomorfolino morpholino or, in each case is replaced with a group R6 - or co(r7o 0R8 (PO), (r7o - R9), co r6o c1-4 alkyl -, bis - (CO r6o c1-4 alkyl) -, (r7o po 0R8 c1-4 alkyl) - or (r7o - R9) - for rent - C1 in 4, the R6 to R9 are defined as mentioned above, a morpholino or homomorfolino Group, which is replaced with two groups r6o co or co r6o alkyd ILO c1-4, or with a Group r6o co and with a Group r6o co c1-4 alkyl,The R6 is defined as mentioned above, a Group pirrolidinilo, piperidinilo or hexahidroazepinilo replaced in position 1 with the radical R10, being replaced the Rings of 5 to 7 members mentioned above, in each case as an atom of Carbo No, with a Group r6o co, (r7o 0R8 (PO), r7o - R9), co r6o c1-4 alkyl -, bis - (CO r6o c1-4 alkyl) -,(r7o po 0R8 c1-4 alkyl) - or (r7o - R9) c1-4 alkyl, the R6 to R10 are defined as mentioned above, a Group pirrolidinilo, piperidinilo or hexahidroazepinilo replaced in position 1 with the radical R10, being replaced the Rings of 5 to 7 members above In each case above, in addition to carbon Atoms.Two groups r6o co or co r6o c1-4 alkyl, or with a Group r6o co and with a Group r6o co c1-4 alkyl R6 and R10, which are defined as mentioned pr