MXPA01007770A - Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them - Google Patents

Abstract

The present invention relates to bicyclic heterocyclic compounds of general formula (I) wherein Ra, Rb, X and Y are defined as in claim 1, the tautomers, stereoisomers and salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, particularly an inhibitory effect on signal transduction mediated by tyrosinekinases, their use in treating diseases, particularly tumour diseases, diseases of the lung and airways and the preparation thereof.

Description

PHARMACEUTICAL PHARMACEUTICAL COMPOSITIONS HETEROCICLES, CONTAIN THESE COMPOUNDS, THEIR USE AND PROCESS FOR PREPARING THEM DESCRIPTION OF THE INVENTION The present invention relates to bicyclic compounds he t e r c c c i c i s of the general formula their tautomers, their stereoisomers and their salts, in particular their physiologically acceptable salts with inorganic or organic acids or bases, which have valuable pharmacological properties, particularly an inhibitory effect on signal transduction mediated by 11 r o s i n a s a a, its use in the treatment of diseases, particularly tumor diseases, diseases of the lungs and respiratory tract, and their preparation. In general formula I above Ra means a hydrogen atom or a C1-4 alkyl group, Rb means a phenyl, benzyl or 1-phenylethyl group in which the phenyl nucleus is substituted in each case by the groups R to R3, while Ri and R2, which may be the same or different, each means a hydrogen atom, fluorine, chlorine, bromine or iodine, an alkyl group of C 1, hydroxy, C 1-4 alkoxy, C 3-6 cycloalkyl, C 1-6 cycloalkoxy, C 2-5 alkenyl or C 2-5 alkynyl, an aryl, aryloxy group , arylmethyl or arylmethoxy, an alkenyloxy group of C3-5 or alkynyloxy of C3-5, while the unsaturated portion may not be linked to the oxygen atom, a group to 1 qu 11 its 1 pheny1 or of C _.-, C 1-4 alkylsulfinyl, C 1-4 alkylsulfonyl, 1 to 1 to 1 to 1 to 1 to 1 to C 1, trif 1 to 1 to 1 to 1 to 1 to 1, trifluoromethyl-sulfinyl to 1 to 1 to 1 its 1 f on i 1 o, a methyl or methoxy group substituted by 1 to 3 fluorine atoms, an ethyl or ethoxy group substituted by 1 to 5 fluorine atoms, a cyano group or nitro, or an amino group optionally substituted by one or two groups ^ n ^ y **? * ti & > ¿Lál? .. * 8 * .., and., .___... ..__ .. _. ^ _, -__ * -__ ,. ,, - * _____ alkyl of C? _4, while the substituents may be the same or different, or Ri together with R2, if they are attached to adjacent carbon atoms, mean a group -CH = CH-CH = CH, -CH = CH-NH or -CH = N-NH, and R3 signifies a hydrogen atom, fluorine, chlorine or bromine, an alkyl group of C? _), Trifluoromethyl or alkoxy of C? _, X and Y together signify a bridge -N = C (-AB) -CH = CH-, -CH = NC (-AB) = CH-, -CH = C (-AB) -N = CH-, -CH = CH-C (-AB) = N-, -N = C (-AB) -N = CH- or -CH = NC (-AB) = N-, where the left end of these bridges is linked to position 5 and the extreme right of these bridges is linked to the 6-position of the pyrimidine ring, A means an -O-alkylene group of C _.- 8, O-C 1 to C 1 -C 7, C 3 -7-C 1 -3-C 3-7 cycloalkylene, C 1 -7-cycloalkylene, or C 4 -C 7 -alkylene -3-O -O-alkylene of C1-3-c 1 c 1 or to 1 qu i 1 e not of C 3 _7 - a 1 qu i 1 ene of C -3, while ^ y ¿^ • - -? "**" * • "* •> • * • -» - * - "- '- - - that the oxygen atom of the aforementioned group in each case is bound to the heteroaromatic ring bicyclic, a group -NR4- to 1 qu i 1 C1-8 ene, -NR-cycloalkylene of C3_7, -NR4 - a 1 qu i 1 in o of C1-3- cycloalkylene of C3-7, -NR4-cic 1 or 1 qui 1 e no of C3-7- alkylene of C1-3 or -NR - a 1 qui 1 e not of C1-3- c 1 c 1 or a 1 qu 11 e no of C3-7 - a 1 The C1-3 ene, while the -NR- portion of the aforementioned groups in each case is linked to the bicyclic heteroaromatic ring, and R4 signifies a hydrogen atom or an alkyl group of C__, an oxygen atom which it is linked to a carbon atom of group B, a group -NR. - c i c 1 or 1 qui 1 e n of C 4 -7 -NH-S 02 - alkylene of Ci-. or - NR4-cyc 1 or 1 to 1 to C4_7- N (C 1-4 alkyl) - S 02 - to 1 qu i 1 e not of C 1-4, while the -NR 4 - portion of the groups above mentioned in each case is linked to the bicyclic heteroaromatic ring, and R4 is as defined above, a group -NR, where the latter is linked to a carbon atom of group B and R4 is as defined as previous, a group azeti di ni 1 e no, pirro 1 i di ni 1 en o, p ip eri di ni 1 en oo hexahi dr oa z ep ini 1 e not optionally substituted by one or two methyl groups, while in each case the The cyclic nitrogen atom of the aforementioned groups is linked to the bicyclic heteroaromatic ring, an azeti di ni 1 en-a 1 qu i 1 group in o of C_-3, pyrro 1 i di ni 1 en - a 1 qu i 1 ene of C? _3, piperidinylene-alkylene of C? _3 or hexah i dr or z ep ini 1 en- to 1 qu i 1 ene of C? -3, while in each case the cyclic nitrogen atom of the groups before mentioned is linked to the bicyclic heteroaromatic ring, a group 1, 4-p ipe azini 1 ene or 1,4-h omop i pe razini 1 eno, these groups being each linked to a carbon atom of group B, a group 1, 4 -p ipe razini 1 en - a 1 qu i 1 ene of Ci- 3, or 1, 4 - h omop ipe razi ni 1 en - a 1 qu i 1 e no of C? -3, while in each case the atom of cyclic nitrogen of the aforementioned groups is linked to the bicyclic heteroaromatic ring, a group -NR4 - a z e t i di n i 1 n, -NR-p i r r o 1 i di n i 1 e, -NR. -p ipe r i di n i 1 e no or -NR4-h ex a h i dr o a z i i i i e no, while the -NR4 portion of the aforementioned groups is linked in each case to the bicyclic heteroaromatic ring and in , aMMM * < ^ -A > ».._.» J ^ cte «cl.« U .. | - »J? .. ^ .., _ ,, .-,. ______.__, ___-___ l___., _. . _- »» _ > - each case the cyclic nitrogen atom of the aforementioned groups is bonded to a carbon atom of group B, a group -NR4 -azeti di ni 1 en - a 1 qu i 1 e not of C1-3, -NR - pyrro 1 i di ni 1 e n- a 1 qu i 1 e not of C? _3, -NR4-piperi di ni 1 en - a 1 qu i 1 e not of C? _3 or -NR - he xa hi dr oa z ep ini 1 en - a 1 qu i 1 e of C _._ 3, while in each case the NR4 portion of the aforementioned groups is linked to the bicyclic heteroaromatic ring and the cyclic nitrogen atom of the aforementioned groups is in each case is linked to the alkylene portion, a -NR4-cic 1 or a 1 qu 11 group in car bon i 1 or of C3_ 7, while the -NR4- portion is linked to the bicyclic heteroaromatic ring and the carbonyl group is bonded to a nitrogen atom of group B, a group -NR4-cic 1 or a 1 qu 11 in ca bon i 1 ami no of C3-7, while the -NR4- portion is linked to the heteroaromatic ring bic cyclic, and the nitrogen atom of the carbonylamino portion, which may be further substituted by a C 1-4 alkyl group, is bonded to a carbon atom of group B, a group -NR. - cic 1 or 1 qui 1 in ca bon i 1 ami no of C3 -7 - a 1 qu i 1 in o of C? -3, while the -NR4-portion is linked to the bicyclic heteroaromatic ring and the Nitrogen from the carbonylamino moiety may be further substituted by a C 1 _ 4 alkyl group, a azeti di ni 1 encar bon i 1, pyrro 1 i di ni 1 enca rboni 1 o, p ipe r 1 di ni 1 enca rbon i 1 oo he xa hi dr oa z ep in 11 en - ca r bon i 1 o, while in each case the cyclic nitrogen atom of the aforementioned groups is bonded to the bicyclic heteroaromatic ring and the carbonyl group in each case is bound to a nitrogen atom of group B, a group azeti di ni 1 in car bon 11 ami no, pyrrolidinylenecarbonylamino, pipepdinilen-carbonylamino or hexahi dr or z ep in 11 e nca rb on i 1 - ami no, whereas in each case the cyclic nitrogen atom of the aforementioned groups is linked to the heteroaromat ring The bicyclic ico and the nitrogen atom of the carbonylamino portion, which may be further substituted by an alkyl group of C ?4, is bonded to a carbon atom of group B, an azetidini 1 group on the 1-amino-alkylene group of C _._ 3, pyrrolidinylenecarbonylamino- ? What is it? The alkylene of C__3, pipe ri di ni 1 in ca rb on i 1 ami no-alkylene of C? _3 or he xahi dr oa z ep ini 1 e nca r boni 1 ami no - a 1 qu i 1 no of C? -3, while in each case the cyclic nitrogen atom of the aforementioned groups is linked to the bicyclic heteroaromatic ring and the nitrogen atom of the carbonylamino portion can be further substituted by a C? -4 alkyl group, and B means a group RßO-CO- a 1 qu i 1 e not -NR 5, (R70-PO-OR8) -alkylene-NR5 or (R7O-PO-R9) -alkylene-NR5 wherein in each case the alkylene portion, which is straight chain and contains 1 to 6 carbon atoms, may be further substituted by one or two alkyl groups of C -2, or by a group RdO-CO or a group RgO-CO-alkyl of C? -2, while R5 means a hydrogen atom, a C1-4 alkyl group, which may be substituted by a hydroxy group, C 1 -4 alkoxy, R60-CO, (R7O-PO-OR8), (R7O-PO-R9), amino, C1-4 alkylamino or di- (C1- alkyl) 4) -amino, or by an alkyleneimino group of 4 to 7 members, while in the alkyleneimino groups of 6 to 7 members mentioned above in each case a methylene group in the nor 1 inii •? - ?? ? 1 I -ne iii 1 t Yrti__i ?? _________________________________ __________________________ ^^ position 4 can be replaced by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, immo or N- (C? _) -? M alkyl group? no, a cycloalkyl group of C3-7 or cycloalkyl of C3_7-alkyl of C? -3, R., R7 and Rs, which may be the same or different, in each case a hydrogen atom, an alkyl group of C1- 8, which may be substituted by a hydroxy group, C 1 -4 alkoxy, ammo, C 1 alkylamino. or di- (C 1-4 alkyl) -amino, or by an alkyleneimino group of 4 to 7 members, while the groups a 1 qu 11 in imi of 6 to 7 members mentioned above in each case a methylene group in the position 4 can be replaced by an oxygen or sulfur atom, by a sulfonyl, sulfonyl, imino or N- (C 1-4 alkyl) -imino group, a C 4-7 cycloalkyl group optionally substituted by 1 or 2 methyl groups , a C3-5 alkenyl group or C3-5 alkynyl, while the unsaturated portion may not be bonded to the oxygen atom, a C3_ cycloalkyl group - C4_4alkyl, aryl, C1-4alkylalkyl or Re CO - O - (RCC Rd), while - '- "*" ". ^.-_ *, * __.__.-___._. --M» a ».3, - .. J __. Faith _ ^ & _. (....- . ^ .... _ _, _.._ > __ .. ,, .._ > g._.. ^ ____________ Rc and R. which may be the same or different, in each case they mean a hydrogen atom or an alkyl group of C? -4 and Re means an alkyl group of C? -, cycloalkyl of C3-7, alkoxy of C? _ or cycloalkoxy of C 5-7, and R 9 signifies an alkyl group of C 4 -4, aryl or aryl-C 1 alkyl, a 4 to 7 membered alkyleneimino group which is substituted by a RdO-CO group, (R70-PO-OR8 ), (R7O-PO-R9) -, R60-CO-alkyl of C? _4, bis- (R? O-CO) -alkyl of C? 4, (R0-PO-OR8) -alkyl of C1-4 or (R7O) - PO - Rg) - at 1 qu i 1 of C _4, where Rg to R9 are as defined above, a piperazino or homop ip erazino group which is substituted at position 4 by the Rio group, and additionally in a cyclic carbon atom by a group R60-CO, (R70-PO-OR8) -, (R70-PO-R9), R60-CO-C1-4 alkyl-, bis- (R60-CO) -alkyl of C1-4), (R70-PO-OR8) -alkyl of C 1-4 or (R7O-PO-R9) -alkyl of C -4, wherein R6 to Rg are as defined in the foregoing and Rio means a hydrogen atom, an alkyl group of C? _, formyl, C1-4 alkylcarbonyl or C 1 _ alkylsulfonyl, -______. _ ___. _. _._., _ ,,. "^ ____" ___. ...... _ ^ __ ^ -_ -___- i_. . . . .. ... at_Ji__j __- il__fa »__" __ ..... and ..... ..., __--. "_, _._-- ..., =, ... Ai _... piperazino group uh omop ipe razi not being substituted in each case in position 4 by a group R60-CO- to 1 qu i 1 or of C i _, bis- (R60-CO) -alkyl of C? -4, (R70-PO-OR8) -alkyl of C? _4 or (R70-PO-R9) -alkyl of C? _4 where R? Rg are as defined in the above, a pyrrolidinyl, piperidinyl or hexahydroaz ep ini 1 o group, substituted at the 1-position by the Rio group, while the aforementioned 5-7-membered rings are each further substituted on an atom of carbon by a group R60-CO, (R70-PO-OR8), (R70-PO-R), R60-CO-alkyl of C i _ 4, bis- (ReO-CO) -alkyl of C i -, (R70-PO-OR9) -alkyl of C i _ o (R7O-PO-R9) -alkyl of C1-4 e where R. to Rio are defined as in the above, a pyrrolidinyl, piperidinyl ohe xa hi dr oaz ep ini 1 o group, substituted in the 1-position by a group R gO-CO-a 1 qu i 1 o of C1-4-, bis- (ReO-CO) -alkyl of C? _4, (R7O-PO-OR9) -C1-4 alkyl or (R70-PO- Rg) - at 1 qu 11 or of C1-4-, where R ea Rg are as defined in the above , a 2-ox or -mo-1-ino-group, which may be substituted by one or two methyl groups, a 2-oxo-mo-1-in-1-o-group, which is substituted at the 4-position by a hydrogen atom, by an alkyl group of C? _, RgO-CO-alkyl of C? _4, (R70-PO-OR8) -alkyl of C? _4, or (R70-PO-R9) - a 1 qu i 1 of C ? _, while Rd to Rg are as defined in the above and the aforementioned 2-oxo-morphinoyl groups are in each case linked to a carbon atom of group A, a C5-7 cycloalkyl group, which is substituted by an amino group, C? - alkylamino or di- (C1-4 alkyl) -amino, and by a group R60-CO, while R? is as defined above, a cycloalkyl group of C5-7, wherein a methylene group is replaced by a group R50-CO-a 1 qu 11 in imide of C1-4, [bis - (R? O - CO) - a 1 qu i 1 Ci-4_ immo, (R7O-PO-ORe) - a 1 qu i 1 in imi no of C1-4 or (R7O-PO - Rg) - a 1 qu i 1 in imi no of C? -, and in each case two hydrogen atoms in the cycloalkyl portion are replaced by a straight-chain alkylene bridge, this bridge contains 2 to 6 carbon atoms, if the two hydrogen atoms are located on the same carbon atom, or contains 1 to 5 carbon atoms if the two hydrogen atoms are located on carbon atoms ** - * - * • 'Adjacent, or contain 2 to 4 carbon atoms, if the two hydrogen atoms are located on the carbon atoms that are separated by an atom, while Rg to Rg are as defined in the above, or A together with B signify a 1-azetidinyl group, wherein the two hydrogen atoms of a methylene group are replaced by a straight chain C4_6 alkylene bridge, while in each case a methylene group on the alkylene bridge of C4-6 is replaced by a group ReO- CO - a 1 qu i 1 in imi of C? _, [bis - (RßO - CO) - a 1 qu i 1 e no C? _4_-imino, (R70-PO-ORg) -alkyleneimino of C? _4 or (R7O- PO- Rg) - a 1 qu i 1 in imi no of C? _4, where Rg to R9 are as defined in the above, a group 1 -pirr ol i di ni 1 o, 1 -p ip eri di ni 1 oo 1 - azacic 1 ohep t - 1 - i 1 or where the two hydrogen atoms of a methylene group are replaced by a straight chain C3_6 alkylene bridge, while in each case a methylene group in the alkylene bridge of C 3 -g is replaced by a group R50-CO- to 1 qui lenimino of C1-4), [bis - (RgO-CO) -alkylene of C1-4)] imino, (R70-PO-OR8 ) C1-4 alkyleneimino or (R7O- PO-Rg) -alkyleneimino of C? _4, wherein R6 to Rg are as defined above, _ iirpr- -11 I a ___ i _____________________? ____________________ É __ ^ a pyrrolidino, piperidino ohe xa hi dr oa z ep ino group, which is substituted in each case by an amino group, alkylamino of C i _ 4 or di- (C 1-4 alkyl) ) -amino, and by a group RgO-CO, while R? is as defined above, a piperazino or homop ipe razino group which is substituted at the 4 position by the Rio group and additionally at a cyclic carbon atom by a group R60-CO, (R70-PO-OR8), (R7O-PO-R9), R60-CO-C1-4 alkyl, bis - (RgO-CO) - a 1 qu i 1 or of C 1 -, (R70-PO-OR8) -alkyl of C? _4 or (R70-PO-R9) -alkyl of C? -4 wherein Rg to Rio are as defined in the foregoing, a piperazino or homop epe ne group that is not substituted in each case in position 4 by a group RgO- CO- a 1 qui 1 of C? _, Bis - (RgO- CO) - a 1 qu i 1 o of C1-4, (R70-PO-OR8) -alkyl of C? _4) or (R7O -PO-R9) -alkyl of C? -, where Rg to Rg are as defined above, or a 2-ox or -mo-1-ino-group, which may be substituted by one or two methyl groups, while that for the aryl portions that are mentioned in the definition of the aforementioned groups is meant a phenyl group which . . ... »_._.-_ .- .. _.._,. ^^^" _._ s. ^ .... tj..i. ^ .. »____ fc _______ L_J -_ ^ -__-- --... _.-.._., _..-._..__, __._.______ i ^^ and j &i can be in each case monosubstituted by Rn, mono-, di- or trisubstituted by R12, or monosubstituted by Rn and additionally mono- or disubstituted by R12. while the substituents may be the same or different and Rn may mean a cyano, carboxy, C 1-4 alkoxycarbonyl, aminocarbonyl, C 1-4 alkylaminocarbonyl, di- (C 1-4 alkyl) -aminocarbonyl group, at 1 qui 1 Sulfonium or C 1, C 1 -C 1 alkylsulfinyl, C 1 -4 alkylsulfonyl, hydroxy, 1 1 and 1 1 onium 1 or C 1 -, trif 1 or r or 1 oi, nitro, amino, alkylamino of C i _ 4, di- (C 1 _) alkyl-amino, at 1 qui 1 car on i 1-ami not of C? -4, N- (C 1 alkyl) 4) - a 1 qu i 1 carboni 1 - ami no of C -4, alkylsulfonylamino of C? _4, N- (alkyl of C? _ 4) - a 1 qu i 1 su 1 f on i 1 ami no de C ? 4, aminosulfonyl, C 1-4 alkylaminosulfonyl or di- (C 1-4 alkyl) -aminosulfonyl, or a carbonyl group which is substituted by an alkyleneimino group of 5 to 7 members, while in the alkyleneimino groups of 6 to 7 previously mentioned members in each case a methylene group in the 4-position can be replaced by an oxygen or sulfur, by a sulfinyl, sulfonyl, imino or N- (C? _) -imino group, and ^^^ R12 means a fluorine, chlorine, bromine or iodine atom, an alkyl group of C?, trifluoromethyl or C? -4 alkoxy, or two R? 2 groups, if they are bonded to adjacent carbon atoms, together mean an alkylene group of C3-5, methylenedioxy or 1,3-bu t adi en- 1, 4 - ileno. Preferred compounds of the above general formula I are those in which Ra, R__, X and Y are as defined in the foregoing, with the proviso that A does not mean a group - NR-cic 1 or a 1 i and not a C4 -7 -NH-S02 -alternatively of C? _4 or -NR4- c 1 c 1 or 1 qu and 1 e of C 4 -7 - N (a 1 qu 11 o of C? _4) - S02- alkylene of C? _, While the -NR4- portion of the aforementioned groups in each case is linked to the bicyclic heteroaromatic ring and R4 is as defined above, and does not mean a group aze 11 di ni 1 ene, pirro 1 idin 11 ene, piperi di ni 1 enoo he x ah i dr or z ep ini 1 e unsubstituted by one or two methyl groups, while in each case the cyclic nitrogen atom of the aforementioned groups is linked to the bicyclic heteroaromatic ring, its tautomers, its stereoisomers and its salts. Particularly preferred compounds of the general formula I are those in which Ra is a hydrogen atom, Rb is a phenyl, benzyl or 1-phenylethyl group, wherein the phenyl nucleus is in each case substituted with the groups Ri to R3, while Ri and R2, which may be identical or different, each represents a hydrogen atom, fluo, chlo or bromine, a methyl, trifluoromethyl, ethynyl or amino, phenyl, phenoxy, benzyl or benzyloxy, or R together with R2, if they are attached to adjacent carbon atoms, means a group -CH = CH-NH or -CH = N-NH and R3 signifies a hydrogen atom, fluo, chlo ob x, X and Y together signify a bridge -N = C (-AB) -CH = CH-, -CH = NC (-AB) = CH-, -CH = C (-AB) -N = CH-, _ ** -_ «.___ > .._. «___-... and .s¡ ___ > ».. -. ^ - ^ _ ^ J« ^ .- ^^., A. -B_A¿.c _ ^ _ ^ f.rrlf¡ | rrtF ^^ É ^ - .. ...-__._- ^ ..., _ t_¿ * _a «« _ _ »__-. . -, .... ^ ^ _ »A_a -CH = CH-C (-AB) = N-, -N = C (-AB) -N = CH- or -CH = NC (-AB) = N- , while the left end of these bridges is linked to position 5 and the right end of these bridges is linked to position 6 of the pyrimidine , A means a group -NR4 - a 1 qu i 1 e not of C1-4 , -NR4-cyclohexylene, -NR4-cyclohexylene-NH-S02-C1-3 alkylene, -NR4- a 1 qui 1 e not of C1-3-cic 1 oh exi 1 e no, -NR4-cic 1 oh e xi 1 in - a 1 qu i 1 e of C? _3 or -NR4 - a 1 qu i 1 e of C 1-3 - cic 1 ohe xi 1 en - a 1 qu i 1 in o of C? _ 3, while the portion -NR4- of the aforementioned groups in each case is linked to the bicyclic heteroaromatic and R4 means a hydrogen atom or a methyl group, a group -NR, the latter being bound to a carbon atom of group B and R4 is as defined in the foregoing, a group pyrro 1 i di ni 1 enoopiperi di ni 1 e not optionally substituted by one or two methyl groups, while in each case the cyclic nitrogen atom of the aforementioned groups is bonded to the bicyclic heteroaromatic , riTrirniHTi r t i 1? • __ • * ______ I ¡jfc < ? Ta _____________ ^ i hiigMM _______ ______ ^^ É ___ i group pipe ri di or 1 -? 1 qui 1 or C -3, while the atom cyclic nitrogen of the abovementioned group is linked to the bicyclic heteroaromatic , a group 1, 4 - piperazine 1 enoo 1. 4- homop i pe ratio 11 e no, these groups each being linked to a carbon atom of group B, a group 1, 4 - piperazine 1 en - a 1 C 1 -2 or 1, 4-h omop ip erazini 1 en - a 1 qu i 1 ene of C? -2, while in each case the cyclic nitrogen atom of the groups mentioned above, is linked to the bicyclic heteroaromatic , a group - NR4 - piperidini-1-ene, while -NR portion of the aforementioned group is linked to the bicyclic heteroaromatic , and the carbon atom cyclic nitrogen of the abovementioned group is linked to a carbon atom of group B, a group -NR4 -pi pe ri di n 11 en - at 1 to 11 e of C? _ 2, while the -NR4 portion of the aforementioned group is linked to the bicyclic aromatic hetero and the cyclic nitrogen atom of the aforementioned group is bonded to the alkylene portion, one group -NR4 - cic ohex 1 i 1 i 1 or bon while -NR4- portion is linked to the bicyclic heteroaromatic car, and the carbonyl group is bonded to a nitrogen atom of group B, a group -NR4 - cic 1 oh exi 1 in car bon i 1 ami no, while the -NR4- portion is linked to the bicyclic omatic heteroa , and the nitrogen atom in the carbonylamino portion is bonded to a carbon atom in group B, a group - NR4 - cic 1 O exi 1 encarboni 1 ami no -alkylene of C _2, while the portion -NR4-is linked to the bicyclic heteroa omático a group piperidini 1 encarb on i1 or while the atom? cyclic nitrogen of the abovementioned group is linked to the bicyclic heteroaromatic and the carbonyl group is bonded to a nitrogen atom of group B, a p ipe ri di or 1 cattail rboi 1 ami no, while the atom cyclic nitrogen g The aforesaid branch is linked to the bicyclic heteroaromatic , and the nitrogen atom of the carbonylamino portion is bonded to a carbon atom of group B, .. * ...._.._.______.______, _.-_, ._._. *,. * _. 1É > dadiU__________________________. a group p ipe i di ni 1 in ca rb on i 1 ami no-alkylene of C? _2, while the cyclic nitrogen atom of the aforementioned group is linked to the bicyclic heteroaromatic ring, and B means a group R gO-CO - a 1 qu i 1 en - NR5, (R70-P0-0R8) -alkylene-NR5 or (R70-PO-R9) - a 1 qu i 1 in-NR5 wherein in each case the alkylene portion, which is straight chain and contains 1 to 4 carbon atoms , it may be further substituted by one or two C grupos _2 alkyl groups or by a RCO-CO group or a RgO-CO- a 1 qu i 1 or a C _ 2 group, while R 5 means a hydrogen atom or a C 1-4 alkyl group, which may be substituted by a group RgO-CO, Rg, R7 and R8, which may be the same or different, in each case meaning a hydrogen atom, an alkyl group of C? -8. a cyclopentyl group, cyclopentane, cyclohexyl, cyclohexyl or 1 -hexylmethyl group, a phenyl group optionally substituted by one or two methyl groups, a 5-indanyl group or a benzyl group optionally substituted in the phenyl portion by one or two methyl groups, and Rg means a methyl or ethyl group, a pyrrolidino or piperidino group, which is substituted in each case by a group R60-CO or RgO-CO-alkyl of C? _4 where Rg is as defined above, a piperazino or homop ip erazi group that is not substituted in each case in position 4 by the group Rio and is further substituted on a cyclic carbon atom by a group RO-CO or RgO-CO-C 1-4 alkyl wherein Rg is as defined above and Rio means a hydrogen atom, a methyl or ethyl group, a piperazino or homop ip erazi group, which is substituted in each case in the 4-position by a group RgO-CO-a 1 qu i 1 or of C? -4, bis- (R60-CO) -alkyl of C1- 4, (R70-PO-OR8) -alkyl of C? _4 or (R7O-PO-R9) -C1-4 alkyl wherein Rg to Rg are as defined above, a pyrrolidinyl or substituted piperidinyl group in the position 1 by the group Rio, which is additionally substituted in each case on a carbon atom by a group RgO-CO or RgO-CO-C1- alkyl wherein Rg is as defined above, -_ ~ - »_ a _._._ .. _ > ._. ^ __aa __. ¿_j ______ Aa * __ c ~ -; .. _ ._, _ "._, .__ s &___. ________ a pyrrolidinyl, piperidinyl or hexahi dr oaz ep ini 1 o substituted in the 1-position by a group R gO-CO-a 1 qu i 1 o of C? _4, bis - (R gO - C 0) - at 1 qu i 1 or C? -4, (R70-PO-OR8) -alkyl of C? _4 or (R7O-PO-R9) -alkyl of C1-4 wherein Rg to R9 are as defined in the above, a group 2 - oxo-mo rfo 1 i no, which can be substituted by one or two methyl groups, a 2-oxo-mo fo 1 ini 1 o group, which is substituted at the 4-position by a hydrogen atom, by a group methyl, ethyl or R60-C0-alkyl of C? _4, while Rg is as defined in the above the groups 2-oxo-mo rfo 1 ini 1 or aforementioned in each case, are linked to an atom of carbon of group A, a cycloalkyl group of Cs-6 which is substituted by an amino group, C? -2alkyloxy or di- (C? _2) alkyl-amine, and by a group RgO-CO, while that Re is as defined as in the above, or A and B together mean a group 1- pyrrolidinyl or 1-p ipe ri di ni 1 or wherein the two hydrogen atoms of a methylene group are replaced by a linear C4-5 alkylene bridge, while each case a methylene group of the alkylene bridge of C -5 is replaced by a group RgO-CO- a 1 qu i 1 e not of C? -imino, where R6 is as defined above, a pyrrolidino or piperidino group which in each case is substituted by a amino group, C alquilo _2alkylamino or di- (C? _2) -amino alkyl, and for a group RgO-CO, while Rg is as defined above, a piperazino or homop iperazi group is not substituted in the position 4 by the group Rio? and further on a cyclic carbon atom by a group R60-CO or RgO-CO- at 1 qui 1 or C? _4 where Rg and Rio are as defined in the above, a piperazine group or homopiperazi not substituted in each case in position 4 by a group RgO-CO- a 1 qui 1 or C? _, bis - (RgO- CO) - a 1 qu i 1 de C? -4, (R70-PO-OR8) -alkyl of C? -4 or (R7O-PO-R9) -alkyl of C1-4 wherein Rg to R9 are as defined above, or a group 2 - oxo-mo rfo 1 ino, which can be substituted by one or two methyl groups, particularly those compounds of the general formula I, wherein Ra means a hydrogen atom, > «Ißria ___ MÉ ______? , üitA _________________ ft_i ______ * __? ^^^ Y ^^ LR means a phenyl, benzyl or 1-phenylethyl group in which the phenyl nucleus is substituted in each case with the groups Ri to R3, while Ri and R2, which may be the same or different, each means a hydrogen atom, fluorine, chlorine or bromine, a methyl, trifluoromethyl, ethynyl or amino group, or Ri together with R2, if they are attached to adjacent carbon atoms, means a group -CH = CH-NH and R3 signifies a hydrogen atom, fluorine, chlorine or bromine, X and Y together signify a bridge -N = C (-AB) -CH = CH-, -CH = NC (-AB) = CH-, -CH = C (-AB) -N = CH-, -CH = CH-C (-AB) = N-, -N = C (-AB) -N = CH- or -CH = NC (-AB) = N- , while the left end of these bridges is linked to position 5 and the right end of these bridges is linked to position 6 of the pyrimidine ring, dUa_u ____________? __ É _____? ____ i? ^ jM _____________ _ A means a group -NR4 - a 1 qu i 1 e not of? C? _4, -NR4-cyclohexyl, -NR4-cyclohexylene-NH-S02-alkylene of C? _3, -NR -me ti 1 en-cic 1 ohe xi 1 e no, -NR -cic 1 ohexi 1 in -me ti 1 enoo -NR4 -me ti 1 en-cic 1 oh exi 1 in -methylene, while the -NR4- portion of the The aforementioned groups in each case is linked to the bicyclic heteroaromatic ring, and R 4 signifies a hydrogen atom or a methyl group, a group -NR 4, the latter being linked to a carbon atom of group B and R 4 is as defined in the foregoing, a pyrro 1 i di ni 1 e no op ipe ri di ni 1 e group not optionally substituted by one or two methyl groups, while in each case the cyclic nitrogen atom of the aforementioned groups, is linked to the ring bicyclic heteroaromatic, a group p ipe ri di ni 1 en - a 1 qu i 1 ene of C? _2, while the cyclic nitrogen atom of the group mentioned above, is linked to the bicyclic orthomatic ring, a group 1, 4 -p ipe r a z i n i 1 e no, this group being linked in each case to a carbon atom of group B, neither. li-T-ifÉ-.i, 11 i lililí li!, ¡__ __ &__ÍÉll______ ___ l__ j ^ a group 1, 4 -p ipe razi ni 1 en - a 1 qu i 1 e no of Ci-2, the atom of cyclic nitrogen of the aforementioned group, being linked to the bicyclic heteroaromatic ring, a -NR4 -p ipe ri di n 11 e group, while the -NR4 portion of the aforementioned group is linked to the bicyclic heteroaromatic ring, and the cyclic nitrogen of the aforementioned group is linked to a carbon atom of group B, a group -NR4-cic 1 oh exi 1 in carbon on 11 ami, while the -NR- portion is linked to the bicyclic heteroaromatic ring, and the nitrogen atom of the ca r bon 11 ami portion is not bonded to a carbon atom of group B, a group - NR4 - cic 1 or hex 11 in charge and 1 ami non-alkylene of C? _2, while the -NR4-is linked to the bicyclic heteroaromatic ring, and B means a group R60-CO-alkylene-NR5, (R7O) - PO-OR 8) - alkylene-NRs or (R 7 O - PO - R 9) - a 1 qu i 1 in - N R 5 wherein in each case the alkylene portion is straight chain and contains 1 to 4 carbon atoms, while that R5 means a hydrogen atom, - "-" "- - • J -c> e __", a _.__ _ ,. .___. ___, - ¿-___ -X ._.__. «- ¡__.__..____ - .., _____, __.___.- __ < __._.____._._, .. l! T __- TMÉ ____ an alkyl group of C? _2, which may be substituted by a group RgO-CO, Rg, means a hydrogen atom, an alkyl group of C? -8, a cyclopentyl group, cyclohexyl, cycloalkyl or 1-cyclohexyl, or a phenyl group optionally substituted by one or two methyl groups , a 5-indanyl group or a benzyl group optionally substituted on the phenyl portion by one or two methyl groups, and R 7, R 8 and R 9, which may be the same or different, in each case mean a methyl or ethyl group, a pyrrolidino group or piperidino, which is substituted in each case by a group R60-C0 or R60-CO-C-2 alkyl, wherein Rg is as defined above, a piperazino group, which is substituted, or in position 4 by a group RgO-CO- a 1 qu i 1 of C? _3, (R70-PO-OR8) C-.3 alkyl, or (R7O-PO-R9) -a C 1 -3 alkyl, wherein Rg to R 9 are as defined above, and a pyrrolidinyl, piperidinyl or hexahydroaz epinyl group substituted at position 1 by a group R60-CO- at 1 qui 1 or C ? -4, bis- (R60-CO) -alkyl of C1-4, (R70-PO-OR8) -alkyl of C i -4 or (R70-PO-R9) -alkyl of C? -4, wherein Rg to Rg are as defined above, a group 2-oxo -mor fo 1 i no, which may be substituted by one or two methyl groups, or A and B together mean a group 1-pyrrole 1 i di ni 1 oo 1-piperidinyl, wherein the two hydrogen atoms of a methylene group are replaced by a straight chain C4-5 alkylene bridge, while each case a methylene group on the alkylene bridge of C4-5 is replaced by a group RgO-CO- a 1 qui 1 e nimi no of C? -2 wherein Rg is as defined above, a piperidino group which is substituted by an amino group and by a group RgO-CO, while Rg is as defined above, a piperazino group , which is substituted at position 4 by a group RgO-CO- a 1 qu i 1 or C? _, where R is as defined above, or a group 2-ox or -mo rfo 1 ino , which may be replaced by one or two methyl groups, their tautomers, their stereoisomers and their salts. More particularly preferred compounds of the aforementioned general formula I are '»-i < »'_-__! • -_ 1 V f -TfFf-t- .-« ti • - -, - _t ._- ^ _ _ .. .... ...- «ate !. a, .A ¿_____ «; __.__....... »^ __ __ * __. _________ «to those where X and Y together signify a bridge -N = C (-AB) -N = CH-, particularly those compounds where Ra means a hydrogen atom, Rb means a phenyl, benzyl or 1-phenylethyl group , wherein the phenyl nucleus is substituted in each case with the groups Rj to R3, while Ri and R2, which may be the same or different, each means a hydrogen atom, fluorine, chlorine or bromine, a methyl group or amino, or Rx together with R2, if they are attached to adjacent carbon atoms, mean a group -CH = CH-NH- and R3 signifies a hydrogen atom, fluorine, chlorine or bromo, X and Y together signify a bridge - N = C (-A- B) -N = CH-, while the left end of this bridge is linked to position 5, and the right end of this bridge is linked to the position 6 of the pyrimidine ring, A means a group - NR4 - a 1 qu i 1 e not of C? _3, -NR4- c i c 1 ohe x i 1 e no o -NR4 - c i c 1 ohe x i 1 e n - NH - S 02 - ethylene, while the -NR4- portion of the groups above mentioned in each case is linked to the bicyclic heteroaromatic ring, and R 4 signifies a hydrogen atom or a methyl group, a group -NR 4, the latter being linked to a carbon atom of group B and R 4 is as defined in the foregoing, a group pyrro 1 i di ni 1 enoop ipe ri di ni 1 ene optionally substituted by a methyl group, while in each case the cyclic nitrogen atom of the aforementioned groups, is linked to the bicyclic heteroaromatic ring, a group piperi di ni 1 e nme ti 1 eno, while the cyclic nitrogen atom is linked to the bicyclic heteroaromatic ring, a group 1, 4 -p ipe razini 1 en o, this group is linked to a carbon atom of group B, and B means a group R60-CO-a 1 qu i 1 in -NR5-, wherein the alkylene portion is straight chain and contains 1 to 4 carbon atoms, while R5 means a hydrogen atom, an alkyl group of C -2, which may be substituted by a group R60-CO-, R6 means a hydrogen atom, iirii-l r • 1 r? t 1 1, lltgMl ^ l < and? a < jlt MMh < (RtM ^ t | ¡tti¿¡ | ^ t ^ ^^^ ei an alkyl group of C? _, Ciciohexilo, phenyl, benzyl or 5-indanilo, a pyrrolidino or piperidino group, which is substituted in each case by a group R60-CO or RgO-CO-alkyl of C? _2, while Rg is as defined above, a piperazino group, which is substituted at the 4-position by a group RgO-CO -me ti 1 oo (R70-PO-ORg) -methyl, wherein Rg is as defined above, and R7 and R8 in each case mean a methyl or ethyl group, a piperidinyl group substituted in the 1-position by a RgO-CO group - to 1 qui 1 o of C? _4, bis- (R60-CO) -alkyl of C_4, (R70-PO-OR8) -methyl or (R70-PO-R8) -ethyl, (R7O-PO-R9) -methyl, wherein Rg to R8 are as defined in the foregoing and Rg signifies a methyl or ethyl group, a 2-ox or -mo-1-pho-1 group, which may be substituted by one or two methyl groups, or A and B signify together a piperidino group which is substituted by an amino group and by a group RgO-CO, while Rg is as defined above, a piperazino group, which is substituted at position 4 by a group R60-CO-a 1 qi 1 or C i - 2, where Rg is as defined above, its tautomers, its eisomers and its salts. The following particularly preferred compounds of the general formula I are mentioned by way of example: (1) 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- (. {1- [(methoxycarbonyl)] methyl] -piperidin-4-yl.}. amino) -pyrimido [5, 4 d] pyrimidine, (2) 4- [(3-chloro-4-fluoro-phenyl) amino] -6- [(trans-4 - { N- [(ethoxycarbonyl) methyl] -N-methylamino.} - cyclohex-1-yl) amino] -pyrimido [5, 4-d] pyrimidine, (3) 4 - [(3-chloro- 4-f luorofenyl) amino] -6- [4- ( { N - [(methoxycarbonyl) methyl] -N-methylamino.} Methyl) -piperidin-1-yl] -pyrimido- [5, 4- d] pyrimidine, (4) 4- [(3-bromophenyl) amino] -6- (. {l- [(methoxycarbonyl) methyl] -piperidin-4-yl} amino) -pyrimid [5, 4-d] pir imi di na, (5) 4- [(3-chlorophenyl) amino] -6- ( { L- [(methoxycarbonyl) methyl] -piperidm-4-yl} amino) -pyrimido [5,4-d] pyrimidine, (6) 4- [(3-methylphenyl) amino] -6- (. {1 l [(methoxycarbonyl) methyl] -piperidin-4-yl} amino) -pyrimido [ 5, 4-d] pyrimidine, (7) 4- [(4-Amino-3,5-dichlorofenyl) a mino] - 6 - (. { 1- [(methox? Carbonyl) methyl] -piperidin-4-? L} amino) -pyrimido [5, 4-d] pyrimidine, (8) 4 - [(4-Amino-3,5-dibromofenyl) amino] -6 (. {1- [(methoxycarbonyl) methyl] -piperidine- 4-yl.}. Amino) -pyrimido [5, 4-d] pyrimidine, (9) 4 - [(Indol-5-yl) amino] -6- (. {1 - [(methoxycarbonyl) methyl] -piperidine] -4-yl.} Ammo) -pyrimido [5, 4-d] pyrimidine, (10) 4 - [(3-chloro-4-fluorophenyl) amino] -6- [(trans-4- { N , N-bis- [(ethoxycarbonyl) methyl] ami no.}. -cyclohex-1-yl) amino] -pyrimido [5, 4-d] pyrimidine, (11) 4 - [(3-chloro-4-fluorophenyl) ) amino] -6- [(trans-4- { N, N-bis- [(methoxycarbonyl) methyl] amino.} - cyclohex-1-yl) amino] -pyrimido [5, 4-d] pyrimidine (12) 4- [(3-chloro-4-fluorophenyl) amino] -6 [(trans-4. {[[(Methoxycarbonyl) methyl] amino]} - cyclohex-1-yl) amino] -pyrimido [5, 4-d] pyrimidine, (13) 4- [(3-chloro-4-fluorophenyl) amino] -6- [N- (trans-4 { N ', N' -bis [(methoxycarbonyl methylamino.} - cyclohex-1-yl) -N-methylamino] -pipmido [5, 4-d] pyrimidine, ..J_j __- c, __. . . . * ,, _ .. ....... .. -.... ^^, * «» ^^ ... ^^? * JtaMítlt * AtiM? Í. ^ _ And ^ t and ..... - .., _, ._, ._.___., _, _____ .. & __ _. . __. _.-? 1tjMg | (14) 4- [(3-bromophenyl) amino] -6- (1- [1, 1-bis (methoxycarbonyl) -methyl] -piperidin-4-yl} amino) -pyrimido [5, 4-d] ] pyrimidine, (15) 4- [(3-bromophenyl) amino] -6- (. {l- [(methoxycarbonyl) methyl] -piperidin-3-yl} amino) -pyrimido [5, 4-d] ] pyrimidine, (16) 4- [(3-chloro-4-fluorophenyl) amino] -6- (1 - [1,1-bis (methoxycarbonyl) methyl] -piperidin-4-yl}. -amino) - pyrimido [5, 4-d] pyrimidine, (17) 4- [(3-bromofenyl) amino] -6- (. {1 - [(diethoxyphosphoryl) methyl] -piper? din-4-yl}. amino) -pyrimido [5, -d] pyrimidine, (18) 4- [(3-bromophenyl) amino] -6- [(1- ({[[(ethoxy) (methyl) phosphoryl] -methyl]. piperidm-4-yl) -amino] -pyrimido [5, 4-d] pyrimidine, (19) 4 - [(3-chloro-4-fluorophenyl) amino] -6-. { [trans-4- (2-oxo-morpholin-4? l) -c? clohex-1-yl] -ami n o} -p i rimido [5, 4 - d] p i imi a n and its salts. The compounds of the general formula I can be prepared, for example, by the following methods: a) reaction of a compound of the general formula ^ • _ - < . ! _-. •• "..l- * ~ *? *» * ¿.y. A, ^ l.? .JÍtl? * T? Hi? Í? ~, And?. ~.? ~ * ~ ~ _-_______ __, _ &g .. "S» J, * _- ... -_ * A_ where Ra and Rb are as defined in i above, X 'and Y' together signify a bridge -N = CZ? -CH = CH-, -CH = N-CZ? = CH-, -CH = CZ ? -N = CH-, -CH = CH-CZ? = N-, -N = CZ? -N = CH- or -CH = N-CZ? = N-, where Zi means an exchangeable group, such as a halogen atom or a sulphinyl or sulphonyl group substituted by, for example a chlorine atom or bromine, a metiisulfinilo group, pr op i 1 its one end 11 or pheny 1 thereof 1 fini 1 or benci 1 thereof 1 fini 1 or, methanesulfonyl, propylsulfonyl, phenylsulfonyl, or its 1-on-1, with a compound of the general formula H -A-B, (111) wherein 'irlTn _ ?? íí ???? f i í í? l_tlt __- ll1ÍÉ__n_Élti? tllM _____ iii? _l? 1Í1 ?? illi i] f [Mjftilulliliiii lint "_____ • _! _____ ______ Eichah ^^ i ^ ßjj A and B are as defined above. The reaction is carried out optionally in a solvent or mixture of solvents such as methylene chloride , dimethylformamide, dimetiisulfóxido, sulfolane, benzene, toluene, chlorobenzene, tetrahydrofuran, be nce no / tetr ah i dr or - furan or dioxane conveniently in the presence of a tertiary organic base such as triethylamine, pyridine or 2 - tell you 1 ami nope ii di na, in the presence of N - eti 1 - di is op r op i 1 ami na (base of Hunig), while these organic bases may also serve simultaneously as solvents, or in the presence of an inorganic base such as sodium carbonate, potassium carbonate or sodium hydroxide, conveniently at temperatures between -20 and 200 ° C, preferably at temperatures between 0 and 150 ° C. b) to prepare a compound of the general formula I wherein at least one of the groups Rg to R8 signifies a hydrogen atom: transformation of a compound of the general formula i -IIT lí_lr? _- I f i r il l _? É ?? i ?? _ ??? r rl Nuil a • - ?? ri Hll 'f |? IWIH, NEFA ?? i | ÉÉl1liiÉÉfafa iiM ^ ^ dM IIM ^ ^ áiÍ__láá_ _tf¡¡_ Í¡_ || ^ ________ É ____ á_k__ _________! _______ ______! R Kv \ / where Ra and Rb are as defined in the above, X "and Y" together signify a bridge -N = C (-AB ') -CH = CH-, 5 -CH = NC (-AB' ) = CH-, -CH = C (-AB ') -N = CH-, -CH = CH-C (-AB') = N-, -N = C (-AB ') -N = CH- or -CH = NC (-AB ') = N-, where 10 A is defined as in the above and B' has the meanings mentioned for B in the above, with the proviso that B 'contains a group R60-CO- , (R70-PO-OR8) - or (R70-PO-Rg) -, wherein Rg is defined as above and at least one of the groups R6 to R8 does not represent a hydrogen atom, by hydrolysis, treatment with acids, thermolysis ohi dr or ge nó 1 is 1 s, in a compound of the general formula I wherein at least one of the groups Rg to 20 R8 means a hydrogen atom. _____-__________ l ____________________ H_i _________ tea For example, functional derivatives of the carboxyl group such as amides unsubstituted or substituted, esters, thioesters, tr ime ti 1 if 111 é esters, orthoesters, imi no é esters, 5 amidines or anhydrides, or the nitrile group, can be synthesized by hydrolysis in a carboxyl group, esters with tertiary alcohols, for example tert-butylester, can be transformed by treatment with an acid or by thermolysis, in a carboxyl group, and esters with aralkanols, for example the benzyl ester, can be transformed by means of a hydrogen ion, in a carboxyl group. The hydrolysis is conveniently carried out, or in the presence of an acid such as hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, trichloroacetic acid, trifluoroacetic acid or mixtures thereof, or in the presence of a base such as lithium hydroxide, sodium hydroxide or potassium hydroxide, in an appropriate solvent such as water, water / methanol, water / ethanol, to gu a / is op r opan or 1, methanol, ethanol , water / tetrahi dr ofura no or gua / di oxa no, at temperatures between -10 and 120 ° C, , _? _f, r _ H, _r_.? '', 1 January liniillfi laiülllll I i ll ^ _ ^ ^ MMt t | MaatM Mijaa ^ ____ ______ É__tt II _ ^^ example at temperatures between room temperature and the boiling point of the reaction mixture. Under the aforementioned reaction conditions, any N-acylamino or N-acylimino groups present such as a N- t r i f 1 uo r o a c e t i i imi no group, can be transformed into the corresponding amino or imino groups. In addition, during treatment with an organic acid such as tricycloacetic acid or trifluoroacetic acid, any alcoholic hydroxy groups present can be transformed into a corresponding acyloxy group, such as the trifluoroacetoxy group. If, in a compound of the formula IV, B 'contains a cyano or aminocarbonyl group, these groups can also be converted to the carboxyl group with a nitrite, for example sodium nitrite, in the presence of an acid such as sulfuric acid, being used at the same time, conveniently as a solvent, at temperatures between 0 and 50 ° C. If, in a compound of formula IV, B 'means, for example, the group tert-bu t i 1 ox i ca r b on 11 o, the tert-butyl group can be ______________ _________ ._, ___ _.__- li li i íiiiriiiiii-liiiÉifiTti • -.? Ea __ "* __" _ * _ "____________ ** ___ _ __ __ * * __ split by treatment with an acid as acid trif 1 uo r or cé ti co, formic acid, p-toluenesulfonic acid, sulfuric acid, hydrochloric acid, phosphoric acid or polyphosphoric acid, 5 op ci on a lme nte in an inert solvent such as methylene chloride, chloroform , benzene, toluene, diethyl ether, tetrahydrofuran or dioxane, preferably at temperatures between -10 and 120 ° C, for example at temperatures between 0 and 60 ° C, optionally thermally, in an inert solvent such as dioxane methylene chloride, chloroform, benzene, toluene, tetrahydrofuran or, preferably in the presence of a catalytic amount of an acid such as p- toluenesulfonic 15, sulfuric acid, phosphoric acid or polyphosphoric acid, preferably at the boiling point of the solvent used, for example, at temperatures between 40 and 120 ° C. Under the aforementioned reaction conditions, Any non-present groups can be transformed into the corresponding amino or imino groups. Yes, in a compound of formula IV, B ' contains the benzyloxycarbonyl group, for example, the benzyl group may also be cleaved by hidrogenol in the presence of a hydrogenation catalyst such as pa 1 to di or / car bon, in an appropriate solvent such as methanol, ethanol, ethanol / water, glacial acetic acid, ethyl acetate, dioxane or dimethylformamide, preferably at temperatures between 0 and 50 ° C, for example at room temperature, and at a hydrogen pressure of 1 to 5 bar. During the hydrogenolysis other groups can be transformed simultaneously, for example a nitro group can be transformed into an amino group, a benzyloxy group in a hydroxy group, and a group N-be nci 1 ami no, N-benci 1 imi no, N - benz 1 oxicaboni 1 ami noo N - benz 1 oxica rb oni 1 -imino, in a corresponding amino or imino group. c) to prepare a compound of the general formula I wherein A means a -NR4-cycloalkylene group of C 4 _7-NH-S 02-CH 2 CH 2 - or -NR 4 -cycloalkylene of C 4-7-N (alkyl) C 1 - 4) - S 02 - C H2 CH 2 and B means a group R60 - CO- to 1 qu i 1 e not of C? -g-NR5, while R4 to Rg are as defined above : Reaction of a compound of the general formula where Ra and Rb are as defined above, X "'and Y"' together signify a bridge 5 -N = C (-A'-H) -CH = CH-, -CH = NC (-A '-H) = CH-, -CH = C (-A' -H) -N = CH-, -CH = CH-C (-A '-H) = N-, -N = C (-A' -H) -N = CH- or 0 -CH = NC (-A '-H) = N-, where A' means a group -NR-cic 1 or a 1 i i e not of C1-7-NH -S02-CH = CH2 or - NR4-cic 1 or 1 qu and 1 ene of C 4 _7 -N (a 1 qu i 1 of C i _ 4) - S 02 - CH = CH 2, while R 4 is as defined as above, with a compound of the general formula R 6 O-CO -alkylene of C ^ -NHRs, (VI) wherein R5 and R6 are as defined above. i - - lili r? .m ??? _ i l i? i? tl?,? 1- | j ^^^? ^^ ______________________________________ ^ The reaction is preferably carried out in a solvent such as methanol, ethanol or isopropanol in the presence of a base such as N-ethyl 1-diis. op r op 1 is at temperatures between 0 and 100 ° C, but preferably at the boiling temperature of the reaction mixture. d) for preparing a compound of the general formula I, wherein B means a group Rg-CO- a 1 qu i 1 en-NR5, wherein the alkylene portion, which is straight-chain and contains 1 to 6 carbon atoms , it may be further substituted by one or two alkyl groups of C? _2 or by a group RgO-CO or RgO-CO- at 1 qui 1 or of C? _2, a piperazino or omop iperazino group substituted at the 4-position by a group RgO- CO - a 1 qu i 1 o of C? -4 obis - (RgO - CO) - a 1 qu i 1 o of C? -4, or a pyrrolidinyl group, piperidinyl ohe xa hi dr oa z ep ini 1 or substituted at position 1 by a group R 60 - CO - at 1 qu i 1 or C? -4 obis - (R gO - CO) - C? -4 alkyl, while in each R5 and R? ? defined are as defined in the foregoing: Reaction of a compound of the general formula where Ra and R are as defined above, X "" e? "together mean a bridge -N = C (-AB") -CH = CH-, 5 -CH = NC (-AB ") = CH -, -CH = C (- - B ") -N = CH-, -CH = CH-C (-AB") = N-, -N = C (-AB ") - N = CH- or -CH = NC (-AB ") = N-, where 10 A is defined as in the above and B" means a group R5NH, where R5 is defined as in the above, a piperazino group uh omop iperazino unsubstituted in the position 4, a pyrrolidinyl, piperidinyl or hexahydride group 1 or 1 or unsubstituted in the 1-position, with a compound of the general formula R60-CO-alkylene-Z2, (VIII) wherein the alkylene portion, which is linear chain and contains 1 to 6 carbon atoms, may be further substituted by one or two ____________? __________ to__________ • - * '' - '' - - - '- --- • ---- * »* * - * .--" - vA- ..___ «». -_i ___ to __._. ____. .. .____ "._ _ ..., ...._ -r ^ ?? ^ t alkyl groups of C? -2 or by a group RgO-CO or RgO-CO-alkyl of C? _2, while that Rg in each case is as defined in the foregoing, and Z2 signifies a changeable integroup, such as a halogen atom or a substituted sulfonyloxy group, for example a chne or bromine atom, a me t 1 group The reaction is optionally carried out in a solvent or a mixture of solvents such as methylene chde, and the reaction is optionally carried out in a solvent or mixture of solvents such as methylene chde. , tell me the title, dimethylsulfoxide, sulfolane, benzene, toluene, chbenzene, tetrahydrofuran, benzene / tetrahydrofuran or dioxane, conveniently in the presence of a tertiary organic base such as triethylamine or N-ethi 1-di is op op 11 ami na (Hunig's base), while they also serve this organic bases at the same time as solvents, or in the presence of an inorganic base such as a solution of sodium carbonate, potassium carbonate or sodium hydroxide, conveniently at temperatures between -20 and 200 ° C, preferably at temperatures between 0 and 150 ° C. ..-_ ... "___.._.__ .. ___fe__ _ _t? ___ i______ii_ __t_______ g ^ e) to prepare a compound of the general formula I, wherein B means a group (R70-PO-OR8) - CH2-NR5- or (R7O-PO-R9) -CH2-NR5-, a piperazino or omopperazino group substituted in the 4-position by a group (R7O-PO-OR8) -CH2 or (R7O-PO-R9) - CH2, or a pyrrolidinyl, piperidinyl or hexah i or a z epinyl group substituted in the 1-position by a group (R70-PO-OR8) -CH2- or (R7O-PO-R9) -CH2-, while that in each R5 and R7 to Rg are as defined in the above: by reacting a compound of the general formula where Ra and Rb are as defined in the above, X "" e and "" together signify a bridge -N = C (- A - B ") -CH = CH-, -CH = NC (-AB") = CH-, -CH = C (-AB ") -N = CH-, -CH = CH-C (-AB") = N-, -N = C (-AB ") - N = CH- or -CH = NC (-AB ") = N-, where A is defined as in the above and B" means a group R5NH, where R5 is defined as in the above, a piperazine group or homop i razino unsubstituted in position 4, a pyrrolidinyl, piperidinyl or hexahi dr oaz ep ini 1 or unsubstituted group in position 1, with formaldehyde or one of its derivatives and a compound of the general formula H- (R7O) PO (OR8), (IX) or C1-4-alkoxy (R7O) (R9), (X) wherein R7 to R9 are as defined above. The reaction is conveniently carried out in a solvent or mixture of solvents such as dioxane, tetrahydrofuran, benzene or toluene, at temperatures between 50 and 150 ° C, preferably at the boiling temperature of the solvent used. f) To prepare a compound of the general formula I, wherein B means a group RβO-CO-CH 2 CH 2 -NR 5, wherein the portion of -CH 2 CH 2 - may be substituted by one or two C1-2 alkyl groups or by a group RgO-CO or R gO-C 0 - a 1 qu i 1 o of C? _2, "" '"-' **" «• * '•» - > - - - - »--- _. ^ J_- _-l_M ---_ ------- .---- and. . _C _. ^ _______._____..___.__.____.__. ^ JJg gj a piperazine or homopoly group not substituted at the 4-position by a group RgO-CO-CH2CH2, wherein the portion of -CH2CH2- can be further substituted in each case by a group RgO-CO or RgO-CO-alkyl of C? _2, or a pyrrolidinyl, piperidinyl or he xahi dr or z ep ini 1 o substituted in the 1-position by a group RO-CO-C H2 CH2, wherein the -CH2CH2 moiety - may be substituted in each case additionally by a group RgO-CO or R gO-CO-a 1 qu i 1 or of C1-2, and R5 and Rβ are defined in each are as defined above: Reaction of a compound of the general formula where Ra and R are defined as in the above, X "" and Y "" together signify a bridge - N = C (- A - B ") - CH = CH -, - CH = NC (-AB") = CH-, -CH = C (- - B ") - N = CH -, Muii mmm? Eth mMiaMto m -CH = CH-C (-AB ") = N-, -N = C (-AB") - N = CH- or -CH = NC (-AB ") = N-, wherein A is defined as in the above and B "means a group R5NH, wherein R5 is defined as in the above, a piperazino or homop p erazino group unsubstituted in position 4, a group p 1 rro 1 i di ni 1, piperidmyl or he xahi dr oa z z 1 or 1 or unsubstituted at position 1, with an acrylate of the general formula CH 2 = CH-CO-OR 6, (XI) wherein the vinyl portion can be replaced by one or two C grupos -2 -2 alkyl groups or by a group RgO-CO or RgO-CO- at 1 qui 1 or C? _2 / and Rg in each case are defined as above. The reaction is preferably carried out in a solvent such as methanol, ethanol or isopropanol at temperatures between 50 and 100 ° C, but preferably at the boiling temperature of the reaction mixture. In addition, a compound of the general formula I can also be prepared, wherein B means a piperidinyl group substituted in the 1-position by a group (R 7 O-P O-OR 8) - C H 2 C H 2, by iTItiftlI 1 rl ni M 1 -1 iu 1 1 I i il nlrtil- - n - -? _M ________ j_g_MÍ ______ g ______ ÍI ___ Í__É __ ^ __L¡__ example, reacting a corresponding compound containing an unsubstituted piperidinyl group in position 1 with a vinylphosphonic acid derivative correspondent. If, according to the invention, a compound of the general formula I which contains a carboxy or hydroxyl group is obtained, it can be transformed, by esterification, into an ester of the corresponding general formula I, or if a compound of the general formula I is obtained wherein B means a group of N- (2-hydroxy-1-di-1-y-1-one or N- (2-hydroxy-1-y-1-yl ester , optionally substituted, this group can be transformed, by cyclization, in a non-corresponding 2-ox or -mo r f or 1 i compound. The subsequent esterification is optionally carried out in a solvent or mixture of solvents such as methylene chloride, dimethylformamide, benzene, toluene, chlorobenzene, tetrahydrofuu, benzene / tetr ah i dr ofur or dioxane or, particularly advantageously, in a corresponding alcohol, optionally in the presence of an acid such as hydrochloric acid, or in the presence of a dehydrating agent, __! _______________________ .... __..._ "_....,. It__ÉHAM.-j. and, for example, in the presence of isobutyl chloroformate, thionyl chloride, triamote 1 c 1 orosi 1 a, sulfuric acid, methanesulfonic acid, p-toluenesulfonic acid, phosphorus trichloride, phosphorus pentoxide, N, N'-di cc 1 ohe xi 1 carb odi imi da, N, N '- di cic 1 ohe xi 1 ca r bodi imi da / N - hi dr oisuccin imi da or 1- hydroxybenzotriazole, and optionally in the presence besides 4-dime ti 1 ami n op iri di na, N, N'-carbonyldiimidazol otrifeni 1 fosfi na / tetrac 1 or carbon uro, conveniently at temperatures between 0 and 150 ° C, preferably at temperatures between 0 and 80 ° C. The subsequent ester formation can also be carried out by reacting a compound containing a carboxy or hydroxyl group, or with a corresponding alkyl halide. The subsequent intramolecular cyclization is optionally carried out in a solvent or mixture of solvents such as acetonitrile, methylene chloride, tetrahydrofuran, dioxane or toluene, in the presence of an acid such as hydrochloric acid or p-toluenesulfonic acid, at temperatures between - 10 and 120 ° C.

In the reactions described above, any optionally present reactive groups, such as hydroxy, carboxy, phosphono, 0-a1, i1-phosphono, amino, alkylamino or imino groups, are protected during the reaction by customary protecting groups, which are unfolded again after the reaction. For example, as protective groups, for a hydroxy group may be the group trimeti 1 if 1 i 1, acetyl, benzoyl, methyl, ethyl, tert-butyl, trityl, benzyl or tetrahydropyranyl, as protective groups for a carboxy group. they may be the group tr ime t 1 if 1 i 1 or, methyl, ethyl, tert-butyl, benzyl or tetrahydr opirani 1 or, as protecting groups for a phosphono group may be an alkyl group such as the methyl, ethyl, isopropyl group or n-butyl, the phenyl or benzyl group, and as protecting groups for an amino, alkylamino or imino group can be the formyl, acetyl, trifl or cetyl, or ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, benzyl, t ox i be nci 1 oo 2, 4 - dime t oxibe n 1, and additionally, for the amino group, a phthalyl group. ~ - "É_l. -» - - »- * - •" • ~? ** »* ... ~ .. ._-_." 4.-l .. »,» J. ¿l? MlÉJ it___Jlh_ > _. ^. . «.., _._...-. - ^ .. «. ^ - i .... ex. , -. ___u_, Any protective group used is optional and subsequently unfolded for example by hydrolysis in an aqueous solvent, for example in water, is op r op to nol / a gua, acid ac é ti co / a gua, tetr there is no water or dioxane / water, in the presence of an acid such as trifluoroacetic acid, hydrochloric acid or sulfuric acid, or in the presence of an alkali metal base such as sodium hydroxide or potassium hydroxide, or aprotic, for example in the presence of y odo trimee 1 if 1 an, at temperatures between 0 and 120 ° C, preferably at temperatures between 10 and 100 ° C. However, a benzyl, methoxymethyl or benzyloxycarbonyl group is split, for example, by hydrolyzing, for example, with hydrogen in the presence of a catalyst such as pa 1 a di / car in an appropriate solvent such as methanol, ethanol, ethyl acetate or glacial acetic acid, optionally with the addition of an acid such as hydrochloric acid, at temperatures between 0 and 100 X, but preferably at temperatures between 20 and 100 ° C. 60 ° C, and at a hydrogen pressure of 1 to 7 bar, but preferably 3 to 5 bar. However, a 2, 4-dimethoxy ib in c 11 o group is preferably split into trifluoroacetic acid in the presence of anisole. A tert-butyl or tertiary-tertiary group is preferably split by treatment with an acid such as trifluoroacetic acid or hydrochloric acid., or by treatment with and without the use of a solvent such as methylene chloride, dioxane, methanol or diethyl ether. A trif 1 or or ceti 1 group is preferably split by treatment with an acid such as hydrochloric acid, optionally in the presence of a solvent such as acetic acid, at temperatures between 50 and 120 ° C, or by treatment with a solution of sodium hydroxide, optionally in the presence of a solvent such as tetrahydrofuran, at temperatures between 0 and 50 ° C. A phthalyl group is preferably split in the presence of hydrazine or a primary amine such as methylamine, ethylamine or n-butylamine, in a solvent such as methanol, ethanol, isopropanol, toluene / water or dioxane, at temperatures between 20 and 50 ° C. . .-,., _.._. -. ..... , --...... . ........... ._._____ * «__., _-__. __ ^ __._-, Í ___ iA ___ ¿tt __-_... c & ..__. ... - ..., __. _!.-.._. .. A simple alkyl group of a 0.0'-dialkylphosphono group is split for example with sodium iodide in a solvent such as acetone, methyl ethyl ketone, acetonitrile or dimethylformamide, at temperatures between 40 and 150 ° C, but preferably at temperatures between 60 and 100 ° C. Both of the two alkyl groups of a 0'-di to 1 qui 1 phosphono group can be cleaved, for example, with yo do trimee 1 if 1 an, br As trime 1 if 1 anooc 1 orotr ime ti 1 s 11 a no and sodium oxide, in a solvent such as methylene chloride, chloroform oacet on it or 11, at temperatures between 0 ° C and the temperature of boiling of the reaction mixture, but preferably at temperatures between 20 and 60 ° C. In addition, the compounds of the general formula I obtained can be separated into their enantiomers and / or diastereomers as mentioned in the above. you can separate cis / trans mixtures in their cis and trans isomers, and the compu these with at least one optically active carbon atom can be separated in their own atoms. Thus, for example, the obtained cis / trans mixtures can be separated by chromatography In their cis and trans isomers, the compounds obtained from general formula I, which are presented as racemates, can be separated by methods known per se in their optical antipodes (see Allinger, NL, and Eli el, EL, in "Topics in Stereochemistry", volume 6, Wiley Interscience, (1971)), and compounds of the general formula I with at least 2 asymmetric carbon atoms, can be separated by virtue of their physicochemical differences, using methods known per se, for example by chromatography and / or fractional crystallization, and, if these compounds are obtained in racemic form, they can then be separated into the enantiomers, as mentioned in the above. The enantiomers are preferably separated by column separation on chiral phases or by recrystallization in an optically active solvent, or by reacting it with an optically active substance which forms salts or derivatives such as, for example, esters or amides, with the compound racemic, particularly acids and their activated derivatives or alcohols, and separation of the mixture of salts or the diastereomeric derivative thus obtained, for example on the basis of different solids, while the free antipodes can be liberated from the salts or pure diastereomeric derivatives by the action of appropriate agents. Particularly optically active acids are, for example, the D and L forms of tartaric acid or dibenzoic acid, di-o-tolyl tartaric acid, malic acid, mandelic acid, canfosuic acid, acid glutamic acid, aspartic acid or quinic acid. As optically active alcohol it can be, for example, (+) - or (-) -mentol, and as an optically active acyl group in amides, for example they can be (+) - or (-) -me nti 1 ox icar bon i 1 o. In addition, the compounds obtained of the formula I can be converted into their salts, and particularly for the pharmaceutical application into their physiologically acceptable salts with inorganic or organic acids. For this purpose acids that may be used include for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid or maleic acid. In addition, if the novel compounds of formula I thus obtained contain a carboxy group, h i dr ox i f o s f o r i 1, sulfo or 5 - t e t r a z o 1 i 1 o, can then be transformed, if desired; in their salts with inorganic or organic bases, and particularly for the pharmaceutical application in their physiologically acceptable salts. The right bases for this purpose, include for example, sodium hydroxide, potassium hydroxide, arginine, cyclohexylamine, ethanolamine, diethanolamine and triethanolamine. The compounds of the general formulas II to XI used as starting materials are known in the literature in some cases or can be obtained by methods known in the literature (see examples I to XX). For example, a starting compound of the general formulas II, IV, V and VII is obtained by successive exchange of interchangeable groups in a corresponding compound, which in turn is obtained according to known methods, for example by introducing halogen into a corresponding hydroxy compound. A compound of the general formula III is obtained by methods known in the literature, for example by reductive alkylation of a corresponding ketone, by alkylation of a ______________________________________ - - "- ** - * corresponding amine, or by addition of an amine to a corresponding alkenyl compound, optionally the subsequent cleavage of protecting groups used As already mentioned in the foregoing, the compounds of the formula General I according to the invention and its physiologically acceptable salts exhibit valuable pharmacological properties, particularly an inhibitory effect on signal transduction mediated by epidermal growth factor receptor (EGF-R), while this can be achieved, for example, by inhibition of ligand binding, dimerization of receptors, or of tyrosine itself, it is also possible that signal transmission is blocked in downstream components.The biological properties of novel compounds are tested as follows: The inhibition of mediated signal transmission by EGF-R can be detected, for example, with cells expressing human EGF-R and whose survival and proliferation depend on stimulation by EGF or TGF-alpha. In this case a cell line dependent on i n t e r 1 e uc i na-3 (IL-3), of murine origin, which had been genetically modified in a way that expressed functional human EGF-R was used. Therefore, the proliferation of these cells, called F / L-HERc, can be stimulated either by murine IL-3 or by EGF (see von Rüden, T., et al. In EMBO J. 1_, 2749-2756 ( 1988) and Pierce, JH, et al., In Science 239, 628-631 (1988)). The FDC-Pi cell line, whose production has been described by Dexter, T.M., and others in J. Exp. Med. 152, 1036-1047 (1980), served as starting material for the F / L-HERc cells. However, cells dependent on another growth factor can also be used alternatively (see for example Pierce, JH, et al., In Science 239, 628-631 (1988), Shibuya, H., et al. In Cell 7_0, 57 -67 (1992) and Alexander, WS, and others in EMBO J.? _, 3683-3691 (1991) .For the expression of the human EGF-R cDNA (see Ullrich, A., et al. In Nature 309, 418-425 (1984)) recombinant retroviruses were used, as described in von Rüden, T., et al., EMBO J. 7_, 2749-2756 (1988), with the difference that it served for the expression of the cDNA of EGF-R the vector lili TW1-Ü ti-i t - > --__% _ ??] ____? _ ?? ni < ??? i Mtt ^, j ^ aÉ »» Ma «M« »« i ^ lÍtt ^ aMfra ^ HÍhMttMteM «^^^^^^^^^^^ h ^^^^^ retroviral LXSN (see Miller, AD and others in BioTechniques 7_, 980-990 (1989)), and as a packaging cell the GP + E86 line (see Markov,? Tz, D., and others in J. Virol. 62_, 1120-1124 (1988). performed as follows: Cultures were cultured at 37 ° C and 5% C02 F / L-HERc cells in RPMI / 1640 medium (B i oWh i 11 a ke r), supplemented with 10% fetal bovine serum ( FCS, Boehringer Mannheim), 2mM glutamine (BioWhittaker), normal antibiotics, and human EGF 20 ng / ml (Promega) To investigate the inhibitory activity of the compounds according to the invention, 1.5 x 104 cells were cultured per well, in triplicate, in 96-well plates, with the previously indicated medium (200 μl), stimulating the proliferation of the cells, either EGF (20 ng / ml), or with murine IL-3. The IL-3 used was obtained from the culture supernatants of the cell line X63 / 0 mi L-3 (see Karasuyama, H., et al. In Eur. J. Immunol.? 8_, 97-104 (1988)) . The compounds according to the invention were dissolved in 100% dimethylsulfoxide (DMSO) and added to the cultures in various dilutions, the maximum concentration of DMSO being 1%. The cultures were incubated for 48 hours at 37 ° C. To determine the inhibitory activity of the compounds according to the invention, it was measured in units O.D. using Cell Titer 96 ™ AQueous N on - Ra di a ct i ve Cell Proliferation Assay (Promega). The relative number of cells was calculated as a percentage of the control (of F / LHERc cells without inhibitor), and the concentration of active substance which 50% inhibited the proliferation of the cells (IC50) was deduced. In this way the following results were obtained: 2 (12) 810 2 (13) 1030 2 (14) 1150 2 (15) 1760 2 (17) 30 2 (19) 129 2 (23) 25 2 (24) 73 2 (26) 21 2 (27) 77 2 (28) 26 3 (4) 58 3 (5) 20 3 (10) 16 3 (12) 103 3 (16) 20 3 (17) 17 3 (18) 40 4 (1) 40 4 (2) 40 The compounds according to the invention of the general formula I therefore inhibit the signal transduction by means of rosin quase, as has been demonstrated in the example of the human EGF receptor, and therefore are useful for the treatment of pathophysial processes that are produced by an over-function of tyrosine quinoa.

These are, for example, benign or malignant tumors, particularly tumors of epithelial origin and neoepithelioma, by metastasis, and the abnormal proliferation of vascular endothelial cells (n e or ng i oge ne s i s). The compounds according to the invention are also useful for the prevention and treatment of diseases of the respiratory tract and the lungs, which are accompanied by an increased or modified mucus production, which is produced by stimulation of tyrosine , as occurs, for example, in inflammatory airways diseases such as chronic bronchitis, chronic obstructive bronchitis, asthma, bronchitis, allergic or non-allergic rhinitis or sinusitis, cystic fibrosis, deficiency of a-1-a 111 r ip si na, or in the case of cough, pulmonary emphysema, pulmonary fibrosis, and hyperactive respiratory tract. The compounds are also suitable for the treatment of diseases of the tract jaaai »_ and -gastrointestinal and of the ducts and the gallbladder, which are accompanied by an altered activity of tyrosine, as occurs, for example, in chronic inflammatory disorders such as cholecystitis, Crohn's disease, colitis ulcerative, and ulcers of the gastrointestinal tract, or as occurs in diseases of the gastrointestinal tract that are associated with increased secretion, such as Menetrier's disease, the dissecting adenoma, and the protein loss syndrome, and edema for the treatment of nasal polyps and polyps of the gastrointestinal tract of various origins, such as, for example, hairy or nasal polyps of the large intestine, but also of polyps in the colon of familial polyposis, in intestinal polyps in Gardner's syndrome, in polyps of the entire gastrointestinal tract in the P eutz-Je gh ers syndrome, in inflammatory pseudopolyps, in juvenile polyps, in the deep cystic colitis, and in intestinal cystoid pneumatosis. In addition, the compounds of general formula I and their physiologically acceptable salts can be used to treat kidney diseases, particularly in the change of ,Y. And you, u.yny. ",," -..... and cystic alterations, for example in cystic kidneys, for the treatment of renal cysts, which may be of idiopathic origin or present in syndromes such as, for example, in tuberculous sclerosis, in the von H i pp syndrome. - L i nda u, in the ne fr on op tisis and balloon-like sarcoma of the kidney, as well as other diseases that are caused by an aberrant function of 11 rosi na qui na sas, such as, for example, hi pr pro 1 epidermal (psoriasis), inflammatory processes, diseases of the immune system or 1 ógi co, hipe rp ro 1 iferación of hematopoietic cells, etc. By virtue of their biological properties, the compounds according to the invention can be applied, alone or in combination with other macologically active compounds, for example in tumor therapy, in monotherapy or in combination with other therapeutic agents. is, for example in combination with topoisomerase inhibitors (e.g. etoposide), inhibitors of mitosis (e.g. vinblastine), with compounds that interact with nucleic acids (e.g. cisplatmo, cic 1 ofosf ami da, adriamycin), antagonists of '• *' __ -__ • _ c_a_a_i__ »hormones (for example tamoxifen), inhibitors of metabolic processes (for example 5-FU etc.), cytokines (for example interferons), antibodies, etc. For the treatment of diseases of the respiratory tract these compounds can be administered alone or in combination with other therapeutic agents of the respiratory tract, such as, for example, substances with s e c r e t t i i t i a t activity, broncholitic and / or inflammation inhibitor. For the treatment of diseases in the region of the gastrointestinal tract, these compounds can be administered by themselves alone or in combination with substances that influence motility or secretions, or substances inhibiting inflammation. These combinations can be administered simultaneously or sequentially. These compounds can be administered, either alone or together with other active substances, intravenously, subcutaneously, intramuscularly, intraretarily 1, int aperitoneally, intranasally, by inhalation or transdermally or orally, while aerosol formulations They are particularly suitable for inhalation. , _ * ____ > _ * -_., __, _ _j_, ____. "._- _._." _, _. ._.____.._._. - r Jff__if * For the pharmaceutical application, the compounds according to the invention are generally used in warm-blooded vertebrates, particularly in human beings, in dosages of 0.01-100 mg / kg of body weight, preferably 0.1-15 mg / kg. For administration, they are formulated with one or more carriers and / or conventional inert diluents, for example corn starch, lactose, sucrose, microcrystalline cellulose, magnesium stearate, po 1 i vi ni lp iro 1 i dona, citric acid, acid tartaric, water, water / ethanol, water / glycerol, water / sorbite 1, a gu a / po 1 ieti 1 eng 1 ico 1, propylene glycol, stearyl alcohol, carboxymethylcellulose, or substances containing fats, such as solid fat , or appropriate mixtures thereof, are made to give customary galenic preparations such as tablets, dragees, capsules, powders, suspensions, solutions, sprays or suppositories. The following examples should explain the present invention in more detail, without limiting it: Preparation of the starting products: E j emp lo I ^ ^^^^^^^^^ g ^^^^^^^ - ^^^^^^^^^^^ j ^^ jr ^^^ r Di c 1 or hi dr ato de 4 - ami no - 1 - [(et ox i ca rb on i 1) me ti 1] _ piperidina Through a solution of 2.36 gd¡e 4 - [(tert-butyloxycarbonyl) amino] -1- [(ethoxycarbonyl me ti 1] Piperine in ethanol is passed through gaseous acid chloride for about 10 minutes.

With this the solution heats up in a manifest manner, and after a short time a thick precipitate forms. The suspension is heated to reflux for a further half hour, whereupon the precipitate dissolves again. The reaction mixture is concentrated by evaporation, taken up with toluene, and concentrated once more by evaporation. The residue is stirred with acetone, filtered with suction, and washed with acetone and diethyl ether. The crystalline, almost colorless product is dried in a desiccator. Yield: 2.15 g (100% of theory) melting point: 156 ° C (decomposition) Mass spectrum (ESI +): m / z = 187 [M + H] + The following compounds are obtained analogously to Example I: (1) 4-Amino-l- [(methoxycarbonyl) methyl] -piperidine x 4.4 trifluoroacetic acid (is carried out with trifluoroacetic acid in methylene chloride 1) X-NMR (200 MHz, DMSO-d6): * = 1.7-2.X (m, 2H), 2.0-2.2 (m, 2H), 3.0-3.4 (m, 3H), 3.45-3.65 (m, 2H), 3.75 (s, 3H), 4.2 (s) , 2H), 8.25 (s at hay, 3H) Calculated: C 29.94 H 3.05 N 4.16 Found: C 31.09 H 3.65 N 4.14 (2) Di c 1 or 4-amino-l- [(propyloxycarbonyl) methyl] -piperidine melting point: 148-154 ° C (decomposition) Mass spectrum (ESI +): m / z = 201 [M + H] + (3) D ic 1 orhi dr ato of 4-amino-l- [( isopropyloxycarbonyl) -methyl] -piperidine melting point: 159-168 ° C Mass spectrum (ESI +): m / z = 201 [M + H] + (4) 4-Amino-l- [(cyclohexyloxycarbonyl) -me 111 ] -piperi di na x 2 tr acid ifluoroacetic (carried out with trifluoroacetic acid in methylene chloride 1), melting point: 133-138 ° C Mass spectrum (ESI +): m / z = 241 [M + H] + (5) Di c 1 or 4-ami no hi - no - 1 - [2- (methoxycarbonyl) ethyl] -piperidine melting point: 213-215 ° C (decomposition) '«¿» -_ ^ 8-ÉJ_E & &___ 3 __? r. JhfcfcL ,.

Mass spectrum (ESI +): m / z = 187 [M + H] + (6) Di c 1 or h i dr a t o 4-amino-l- [3 i (methoxycarbonyl) propyl] -piperidine melting point: 170-172 ° C Mass spectrum (El): m / z = 200 [M] + '(7) D ic 1 or hi dr ato de trans - 4 - ami no - 1 - . { N - [(methoxycarbonyl) -metill-N-methylamino} -c? clohexane Rf value: 0.15 (silica gel, methylene chloride / methanol / aqueous solution of araon ia co concentrate = 90: 10: 1) Mass spectrum (ESI +): m / z = 201 [M + H] + (8) D ic 1 orhi dr ato de tans - 4 - ami no - 1 -. { N - [2 - (methoxycarbonyl) -ethyl] -N-methylamm} -cyclohexane Rf value: 0.16 (silica gel, methylene chloride / methanol / concentrated ammonia aqueous solution = 90: 10: 1) Mass spectrum (ESI +): m / z = 215 [M + H] + (9 ) D ic 1 orhi dr ato de trans - 4 - ami no - 1 -. { N - [3 - (methoxycarbonyl) -propyl] -N-methylamino} -ciciohexane melting point: 170-190 ° C (decomposition) Mass spectrum (ESI +): m / z = 229 [M + H] + (10) l-. { 1- [2- (Ethoxycarbonyl) ethyl] -pi p.e ri-di n-4-i 1} -pi pe razi na x 3 trifluoroacetic acid1 (carried out with trifluoroacetic acid in methylene chloride) melting point: 183-186 ° C (decomposition) Calculated: C 39.29 H 4.95 N 6.87 Found: C 39.01 H 4.97 N 7.03 (11) 4- ( { N - [(Methoxycarbonyl) methyl] -Nmyl-ami no.} Me ti 1) - p ipe ri di na x 2 trifluoroacetic acid (carried out with trifluoroacetic acid in methylene chloride) (12) 4-. { [2- (Methoxycarbonyl) -piperidin-1-y1] me t i 1} -p ipe ri di na x 2 trifluoroacetic acid (is carried out with trifluoroacetic acid in methylene chloride) Rf value: 0.30 (silica gel, methylene chloride / methanol / concentrated ammonia aqueous solution = 90: 10: 0.1 ) (13) 4 -. { [2 - (Methoxycarboni 1) -pi r r ol ol idin- 1 - 11] me t i 1} - piperidinax 2 trifluoroacetic acid (is carried out with trifluoroacetic acid in methylene chloride 1 and not) Rf value: 0.13 (silica gel, methylene chloride / methanol / concentrated ammonia aqueous solution = 90: 10: 0.1) (14) 4- ( { 4- [(Ethoxycarbonyl) met? L] -pi pe razin - 1 - i 1.} Me ti 1) -pi pe ri di na x 2 trifluoroacetic acid (is carried out with trifluoroacetic acid in methylene chloride) Rf value: 0.18 (silica gel, methylene chloride and no / meta no 1 / s or aqueous ammonia concentrate = 90: 10: 0.1) (15) trans -4-amino-l-. { N- [(ethoxycarbaryl methyl] -N- (2-hydroxy-2-methyl-prop-1-yl) -amino.} - cyclohexane x 2 trifluoroacetic acid (The reaction is carried out with trifluoroacetic acid in methylene chloride ) R f: 0.75 (reverse phase TLC plate (E. Mer (ck), acet on itri 1 o / a trifluoroacetic acid / = 50: 50: 1) Mass spectrum (ESI +): m / z = 273 [M + H] + E l emp II II - [(et oxycarbonyl) methyl] -4- (2-aminoethyl) -piperidine dihydrochloride 1.0 g of 1- [(ethoxycarbonyl) methyl] -4- (cyanomethyl) -piperidine hydrochloride are dissolved in 15 ml of ethanol and 1.0 ml of ethanolic hydrochloric acid, and are hydrogenated in a Parr apparatus, in the presence of 0.15 g of palladium (10% on activated carbon) as catalyst, at 50 ° C and a hydrogen pressure of 3.5 bar , until the calculated amount of hydrogen has been extracted. The catalyst is filtered off and the filtrate is concentrated by evaporation. It is collected with acetone ___ M__É _____ aÉ_í __l_________i___i_____ ^^^^ g residue, and ethanolic hydrochloric acid is added by drip, until the dichlorhydrate is precipitated. The precipitate is filtered with suction, washed with acetone and diethyl ether, and dried in a desiccator.1 Yield: 760 mg (66% of theoretical) Rf value: 0.22 (silica gel, to 1 uene / dioxane / me) tano 1 / s or 1 aqueous ammonia concentrate = 20: 50: 20: 2) E emplo III Di c 1 o r h i dr a t of 3 -. { 4 - [2 - (me t oxi carb on i 1) eti 1] -piperidin-1-yl) -pyrrolidine To a solution of 4.4 g of N-benzyl-3-pyrrolidinone in 45 ml of methanol is added 5.3 g of 4 - [2 - (me t ox ica rb on i 1) - eti 1] -pi pe ri di na and 2.07 g of sodium acetate. Then add 1.61 g of sodium cyanoborohydride, and the reaction mixture is stirred for three days at room temperature. To carry out the treatment, the reaction mixture is concentrated by evaporation, and the residue is stirred with saturated aqueous sodium hydrogen carbonate solution. The aqueous phase is extracted with ethyl acetate, the combined extracts are washed with water and with saturated sodium chloride solution, dried over sodium sulfate, and "- * - - * -" concentrate by evaporation. The crude product is purified by chromatography through a column of silica gel with methylene chloride and no / methylene chloride (9: 1). Yield: 5.60 g (67% of theory) of N-benzyl-3-. { 4- [2- (methoxycarbonyl) ethyl] -piperidm-1-yl] -: pyrrolidine as a yellowish oil. Rf value: 0.54 (silica gel, methylene chloride / methanol = 9: 1). To unfold the benzyl protecting group, 5.4 g of the obtained product are dissolved in 100 ml of methanol, acidified with IN hydrochloric acid, and hydrogenated in a Pjarr apparatus, in the presence of 1.5 g of palladium (10% strength, active carbon). ), at room temperature and a hydrogen pressure of 3.5 bar. The catalyst is filtered off, the filtrate is concentrated by evaporation, and the brownish crystalline product is dried in a desiccator. Yield: 5.10 g (100% of theoretical) Rf value: 0.56 (thin layer RP-8 plate prepared for reverse phase (E. Merck), methanol / 5% aqueous solution of sodium chloride = 6: 4).

E j empl o IV AA ^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ 4- [(ter.butyloxycarbonyl) amino] -1- [( ethoxycarbonyl) -t-methyl] -piperidine To 2.00 g of 4 - [('ter -bu ti 1 -oxica bon i 1) ami no] -pipe ri-di na in 15 ml of acetonitrile are added, at room temperature, 1.36 ml of ethyl bromoacetate and 2.77 ml of triethylamine. The reaction mixture is stirred for approximately two hours at 65 ° C, resulting in a clear solution. The solvent is distilled off using a rotary evaporator I, the residue is stirred with ice water and made alkaline with a small amount of potassium carbonate solution. The precipitate thus formed is filtered off with suction and the aqueous phase is extracted with ethyl acetate. The combined extracts are washed with water and with saturated sodium chloride solution, dried over magnesium sulfate and concentrated by evaporation. The residue is combined with the precipitate extracted by filtration, washed again with water, and dried in a desiccator. | Yield: 2.40 g (84% of theory) melting point: 76-79 X Mass spectrum (ESI +): 309 [M + Na] + The following compounds are obtained :) in a manner analogous to Example IV: (1) 4 - [(tert butyloxycarbonyl) amino] -1- [(methoxycarbonyl) methyl] -piperidine melting point: 96-98 ° C Rf value: 0.21 (silica gel, cyclohexane / ethyl acetate = 1: 1) (2) 4 - [(tert.butylox? Carbonyl) amino] -1- [(propyloxycarbonyl) -methyl] -pipepdine melting point: 97-99 ° C Mass spectrum (ESI +): 323 [M + Na] + (3) 4- [(tert.butyloxycarbonyl) amino] -1- [(isopropyloxycarbonyl) -methyl] -piperidine melting point: 94-96 ° C Mass spectrum (ESI +): 323 [M + Na] + ( 4) 4 - [(tert.butyloxycarbonyl) amino] -1- [(cyclohexyloxycarbonyl) methyl] -piperidine melting point: 102-104 ° C Mass spectrum (ESI +): 363 [M + Na] + (5 ) 4- [(tert.butyloxycarbonyl) amino] -1- [3- (methoxycarbonyl) -propyl] -piperidine Rf value: 0.75 (silica gel, methylene chloride / methanol / aqueous ammonia solution concentrated = 90: 10: 0.1) Mass spectrum (ESI +): 301 [M + H] + (6) trans-4- [(tert.butyloxycarbonyl) amino] -1-. { N - [(methox? Carbonyl) methyl] -N-methylamm} -cyclohexane Rf value: 0.65 (silica gel, me 111 chloride and no / me t 1 / s or 1 aqueous ammonia concentrate = 90: 10: 1) Mass spectrum (ESI +): 301 [M + H] + (7) trans -4 - [(tert.butyloxycarbonyl) amino] -1-. { N - [3- (methoxycarbonyl) propyl] -N-methylamm} -cyclohexane Rf value: 0.50 (silica gel, me 111 ene / me tano 1 / aqueous ammonia chloride concentrate = 90: 10: 1) Mass spectrum (ESI +): 329 [M + H] + (8) l- [(Ethoxycarbonul) -me 111] -4- (cyan ome ti 1) -p ipe ri di na (l) hydrochloride (after reacting the obtained unpurified product to form the hydrochloride). melting point: 131-136 ° C Rf value: 0.67 (silica gel, methylene chloride / methanol no 1 / aqueous ammonia concentrate = 95: 5: 1) (9) trans - 1 - [(tert-Butyloxycarbonyl) amino] -4-. { N - [(ethoxycarbonyl) methyl] -N- (2-hydroxy? -2-methyl-p r op-1-i 1) -amino} - cic 1 hexa no Rf: 0.75 (silica gel, methylene chloride 1 and no / me tano 1 / concentrated aqueous ammonia 90: 10: 1) Mass spectrum (ESI +): m / z = 373 [ M + H] + T h e lo V 4- [(tert.butyloxycarbonyl) amino] -1- [2- (methoxycarbonyl) ethyl] -piperidine A 5.00 g of 4- [(tert.-butyloxycarbonyl) -amino] -piperidine in 20 ml of methanol 6.45 g of methyl acrylate are added. The reaction mixture is stirred for 7.5 hours at 70 ° C. Once the reaction has ended, the reaction mixture is concentrated by evaporation, leaving a white solid. Yield: 7.09 g (99% of theory) melting point: 91-93 ° C Mass spectrum (ESI +): 287 [M + H] + The following compounds are obtained analogously to Example V: (1) trans - A - [(tert.butyloxycarbonyl) amino] -1-. { N - [2- (methoxycarbonyl) ethyl] -N-methylamino} -cyclohexane _l __? ____ S__i_? XZj ^^ pj Rf value: 0.55 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia solution = 90: 10: 1) ' Mass spectrum (ESI +): 315 [M + H] + (2) 1 -. { 1 - [2- (Ethoxycarbonyl) ethyl] -piperidin-4-11} -4- (tert-butyl-oxycarbonyl) -piperazine Rf value: 0.29 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia solution = 95: 5: 1) The trans-4- [(tert.butyloxycarbonyl) amino] -1- (methylamino) -cydohexane is heated for some minutes at 50 ° C, with stirring, a suspension of 26.30 g of t ra ns -4- [(tert.butyloxycarbonyl) amino] -1- [N- (trifluoromethyl ca rb oni 1) -N -me ti 1 ami no] -cyclo 1 ohe x anus in 250 ml of methanol, until a clear solution results. Then, 50 ml of 2N sodium hydroxide are added with stirring. A slightly cloudy solution is formed, which is stirred for an additional 2.5 hours at room temperature. The reaction mixture is concentrated by evaporation, the residue is taken up in 2N citric acid solution, and extracted with methylene chloride / methanol (9: 1). Then c ^^^ ___-__.

The mixture is made alkaline with 2N sodium hydroxide, and extracted again with methylene chloride and sodium chloride (1: 9: 1). The combined extracts are dried over magnesium sulfate and concentrated by evaporation. Yield: 16.00 g (86% of theory) melting point: 120-122 ° C Mass spectrum (ESI +): 229 [M + H] + Example VII trans - [[(tert.butyloxycarbonyl) amino] -1- [N- (tri-fluoromethylcarbonyl) -N-methylamino] -cydohexane To a suspension of 27.10 g of trans-4- [(tert.butyloxycarbonyl) amino] - 1 - [(trifluoromethyl-c ar boni 1) ami no] - cyclohexane in 220 ml of dime ti 1 fo rmami da 4.54 g of sodium hydride are added in portions, with stirring and at room temperature. The reaction solution, which is slightly turbid, is stirred at room temperature for about 20 minutes, and after this drip is added, cooling with a bath with ice, 6.47 ml of methyl iodide, whereby a colorless precipitate forms slowly. . The reaction mixture is stirred overnight at room temperature, and then, to , Dti? &T perform the treatment, pour over 750 m11 of I water with ice, and neutralize with citric acid.

The resulting precipitate is filtered off, washed with water, and dried in a desiccator. Yield: 26.40 g (93% of theory) melting point: 158-166 ° C Rf value: 0.75 (silica gel, methylene chloride / methanol = 95: 5) EXAMPLE VIII trans - [[(tert.butyloxycarbonyl) amino] -1- [(trifluoromethylcarbonyl) amino] -cciohexane A 22.10 g of l-amino-4- [(tert.butyloxycarbonyl) amino] -cciohexane in 110 ml of Methanol is added dropwise, while cooling with an ice-bath, 10.56 ml of trifluoromethoxane methyl acetate, whereupon a white precipitate forms. The ice bath is then removed and the reaction mixture is stirred for an additional 3.5 hours at room temperature. The resulting precipitate is filtered off, washed successively with 50 ml of ice-cooled methanol, and a small amount of diethyl ether, and dried in a desiccator. Yield: 27.26 g (85% of theory) melting point: 245-246 ° (decomposition) Rf value: 0.4 (silica gel, chloride.) Of me ti 1 e no / me tano 1 = 95: 5 ), E npt I IX I N- (3-aminopropyl) -sarcosine ethyl ester hydrochloride To a solution of 6.10 g of N- [3- (tert.-butyloxycarbonylamino) propyl] -sarcosine ethyl ester in 40 ml of sodium chloride. methylene is added dropwise, while cooling in a bath with ice, 20 ml of trifluoroacetic acid. Next, the reaction mixture is stirred for about three more hours at 0 ° C, until the evolution of gases ends. In order to carry out the treatment, the solvent is substantially eliminated, it is substantially extracted by vacuum distillation using a rotary evaporator. The residue is extracted in a solution of ethereal hydrochloric acid, and again concentrated to dryness by evaporation. Yield: 4.72 g (86% of theoretical) Rf value: 0.0 (silica gel, acetonitrile / water / trifluoroacetic acid = 50: 50: 1) Mass spectrum (El): m / z = 174 [M] + Nitrogen ethyl ester of N - [3 - (ter bu oxoxy bon i 1 ami no) -propyl] -sarcosine To a mixture of 11.55 g of ethyl ester hydrochloride of sarcosine and 28.8 ml of Hunig's base in 200 ml of acetonitrile is added dropwise, while cooling with an ice bath, and in the space of 30 minutes, a solution of 17.90 g of 3- (ter. bu ti 1 ox i ca r boni 1 ami no) pr op i 1 or in 50 ml of acetonitrile. The reaction mixture is allowed to return to room temperature overnight in an ice bath. The solvent is then distilled off on a rotary evaporator, the residue is taken up in tert-butyl methyl ether and washed with ice-cold water. The organic phase is dried over magnesium sulfate and concentrated by evaporation. The crude product is chromatographed on a column of silica gel, with chloride. of methylene / methanol / concentrated aqueous ammonia solution (100: 2: 0.1). Yield: 20.62 g (30% of theory) ^^^ gj ^^ j &? ^^^ * ^ < X Rf value: 0.50 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia solution = 20: 1: 0.1) Mass spectrum (ESI +): m / z = 275 [M + H] + E n e lo XI 4- [(3-chloro-4-fluorophenyl) amino] -6-. { 4 - [(tert-butyl-oxycarbonyl) -amino] -4- (methoxycarbonyl) -p? Peridin-1-yl} -pyrimido [5, 4-d] pyrimidine A 676 mg of 4 - [(3-c 1 -o-4-fluoro-phenyl) -amino] -6-methylsulfin-l-pyrimido [5, 4-d] -pyrimidine and 0.42 ml of triethylamine in 10 ml of dioxane is added 1.03 g of 4- [(tert.butyloxycarbonyl) -amino] - A - (methoxycarbonyl) -piperidine, and the reaction mixture is refluxed for one hour. The reaction mixture is concentrated by evaporation, and the residue is taken up in methylene chloride. The solution is washed with dilute potassium carbonate solution and with water, dried over magnesium sulfate and concentrated by evaporation. The crude product is purified by chromatography through a column of silica gel with methylene chloride and no / methylene chloride (98: 2). Yield: 750 mg (71% of theory) --__. ... «__. > < -_a_- < .M_ > _............ ».. ^. J ^. > _______________ melting point: 186-189 ° C (decomposition) Mass spectrum (ESI +): m / z = 532, 534 [M + H] + The following compounds are obtained analogously to Example XI: (1) 4 - [(3-cl or o- 4 -f luor of eni 1) ami no] - 6 - (N- { Trans - A - [(tert-butyloxycarbonyl) amino] -c? Clohex-1-yl} -N-methylammo) -pyrimido- [5, 4-d] pyrimidine melting point: 202.5 - 204.5 ° C Mass spectrum (ESI +): m / z = 502, 504 [M + H] + (2 ) 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- [N- (trans-4-methylamino-cyclohex-1-yl) -N-methylamino] -1-pyrimido- [5, 4-d] pyrimine Rf value: 0.30 (silica gel, no 1 / no ox a / me t an ion 1 / s or 1 aqueous ammonia concentrate = 20: 50: 20: 10) Mass spectrum (ESI +) : m / z = 416, 418 [M + H] + (3) 4- [(3-bromophenyl) amino] -6-. { [1- (tert-butyloxycarbonyl) -piperidm-4-yl] amino} - pipmido [5, 4-d] pyrimidine melting point: 205 X Mass spectrum (ESI +): m / z = 500, 502 [M + H] + (4) 4 - [(3-bromophenyl) amino] - 6- '. { [1- (tert.butyloxycarbonyl) -piperidin-3-yl] amino} - pyrimido [5, 4-d] pyrimidine melting point: 218 ° C (decomposition) Mass spectrum (The m / z 499, 501 M Use XII 4- [(tertbutyloxycarbonyl) amino] - A - (methoxycarbonyl) -piperidine 2.44 g of l-benzyl-4- [(tert.butyloxycarbonyl) amino] - A - (methoxycarbonyl) '- piperidine are hydrogenated in 20 ml of methanol, in the presence of 300 mg of palladium (10% on activated carbon) as a catalyst, at room temperature and a hydrogen pressure of 3.5 bar during the r 22 hours, until the calculated amount of hydrogen has been absorbed. The catalyst is filtered off and the filtrate is concentrated by evaporation. Yield: 1.72 g (95% of theory) R value: 0.15 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia solution = 90: 10: 1) Mass spectrum (ESI +): m / z = 259 [M + H] + The thirteenth l-benzyl-4- [(tert.butyloxycarbon l) amino] -4 (methoxycarbonyl) -piperidine To a suspension of 5.05 g of 4-amino-lb-1 -4- (meth. rboni 1) -piperi di na in 80 ml of methylene chloride are added 3.97 g of di-ter pirocar bona to. bu t i 1 o. Subsequently, 16 ml of 2N sodium hydroxide are added dropwise with stirring at room temperature, whereupon a precipitate is formed which is in the aqueous phase. After one hour, the organic phase is removed by separation, dried over magnesium sulfate and concentrated by evaporation. Since the unpurified mixture of the product obtained still contains starting material, it is dissolved in 30 ml of tetrahydrofuran, mixed with 1.50 g of p i r o c a b a t o di di t e r. bu t i 1 o and a spatula tip of 4-d ime 111 ami n o - p i r i d a n, and bring it to reflux for three hours. The reaction mixture is concentrated by evaporation, whereby a brown ream remains, which is reacted further without further purification. Yield: 2.64 g (48% of theory) Rf value: 0.65 (silica gel, methylene chloride or aqueous 1: 1 aqueous ammonia solution = 90: 10: 1) Mass spectrum ( ): m / z = 348 [M] + E j us XIV 1- (tert.butyloxycarbonyl) - A - ( { N - [(methoxycarbonyl) | -methyl] -N-methylamino.} methyl) -pipepdine First, 11.0 g of sarcosine methyl ester hydrochloride are transformed into the free base by treatment with 10% potassium carbonate solution 1. It is then heated for six hours to a free base in a pressure vessel, together with 2.0 g of (1-tert.butyloxycarbo-n 11) -4 - [(methylsulfonyloxy) methyl] -piperidine, a 110 ° C and at a pressure of 2 bar. The reaction mixture is then removed from the pressure vessel by washing with methanol and concentrated by evaporation. There is a brown oil, which is washed with a small amount of water. The aqueous phase is removed by separation, and the organic phase is diluted with methylene chloride, dried over sodium sulfate and freed from the solvent using a rotary evaporator. The unpurified product obtained is reacted further without further purification. Yield: 2.49 g of brownish oil The following compounds are obtained analogously to Example XIV: (1) l-tert.but.loxycarbonyl-4-. { [2- (methoxycarbonyl) -piperidin-1-yl] methyl} -piperidine Rf value: 0.86 (silica gel, pet ether 1 eo / ethyl acetate / methanol = 10: 10: 1) Mass spectrum (ESI +): m / z = 341 [M + H ] + (2) 1-tert.but.loxycarbonyl-4-. { [2- (methoxycarbonyl) -pyrrolidin-1-yl] methyl) -piperidine Rf value: 0.74 (silica gel, ether, petr or 1 eo / ethyl acetate / methanol = 10: 10: 1) Mass spectrum (ESI +): m / z = 327 [M + H] H (3) 1-ter. butyloxycarbonyl-4- ({4- [(ethoxycarbonyl) methyl] -piperazin-1-yl} methyl) -piperidine Rf value: 0.69 (silica gel, methylene chloride / methanol = 9: 1) Spectrum of mass (ESI +): m / z = 370 [M + H] + Example XV 4- [(3-chloro-4-fluorophenyl) amino] -6- ( { Trans - A - [(2-hydroxyethyl) amino] -cyclohex-1-yl.} Amino) -pyrimido - [5, 4-d] pyramine A 1.16 g of 4- [(3-chloro-4-f-loropheroyl) -amino] -6- [trans-4-amino-cyclohex-l-yl] amino] -pyrimidine [5,4-d] pyrimidine in 8 ml of acetonitrile are added at room temperature 0.23 ml of 2- f ^^^^^ ¡& * ^ &^ ^ bromoethanol and 0.61 ml of di i s op r op i 1 - e t i 1 ami na¡. The resulting mixture is refluxed. After approximately 5 hours, 0.05 ml of 2-b romocene 1 is again added, and another eight hours are heated until the reaction is complete. The suspension is concentrated, ice water is added to the residue, slightly alkalinized with sodium hydroxide, and filtered with suction. The residue of the still wet filter is collected with methylene chloride / methanol. The cloudy solution is washed with water, dried over magnesium sulfate and concentrated by evaporation. The yellow crude product is triturated with approximately 30 ml of methanol, briefly heated to boiling, cooled slightly, filtered by suction, and then washed with cold methanol. Yield: 990 mg (76% of theory) melting point: 165-172 ° C Mass spectrum (ESI +): m / z = 432, 434 [M + H] + The following compound is obtained analogously to Example XV : (1) 4- [(3-chloro-4-fluorophenyl) amino] -6- (4 -. {[[(2-hydroxyethyl] -amino] methyl.}. -p? Peridin-1-yl ) - pyrimido [5, 4-d] pyrimidine Rf value: 0.50 (gel of sIJ, to 1 that no / di ox ano / me t ano 1 / s or 1 aqueous ion of concentrated ammonia = 20: 50: 20: 3) Mass spectrum (ESI + ): m / z = 432, 434 [M + H] + E pb XVI 4- [(3-chloro-4-f luorofenyl) amino] -6- [N- (t ra ns - A -aminocyclohex-1 -yl) -N-methylamino] -pyrimido [5, 4 -d] pyrimidine A 2.10 g of 4 - [(3-c 1 oro-4-fluoro-phenyl) amino] -6- N-. { trans-4- [(tert.butyloxycarbonyl) amino] -cyclohex-l-yl} -N-methylamino) -pyrimido- [5, 4-d] pyrimidine in 30 ml of methylene chloride, logs are added dropwise to 3.0 ml of trifluoroacetic acid. The reaction mixture is stirred for 1.5 hours at room temperature, it is suggested to stand overnight, and it is concentrated by evaporation the next morning. The residue is taken up in methylene chloride / methanol (5: 1), washed with 2N sodium hydroxide and with water, dried over magnesium sulfate and concentrated by evaporation. The yellow unpurified product is triturated with diethyl ether, filtered with suction and dried under vacuum. Yield: 1.60 g (95% of theory) melting point: 203-205 ° C ** g ^ ^^^^^^^^^ £ ^^ * gl ^ ií ji Mass Spectrum (ESI +): m / z = 402, 404 [M + H] + The following compounds are obtained from Analogous to Example XVI: (1) 4- [(3-bromophenyl) amino] -6- [(piperidin-4-yl) amino] -pyrimido [5, 4-d] pyrimidine melting point: 215 ° C Spectrum mass (ESI +): m / z = 400, 402 [M + H] + (2) 4- [(3-bromophenyl) amino] -6- [(piperi, din-3-yl) amino] -pyrimido [ 5, 4-d] pyrimidine melting point: 178 ° C Mass spectrum (ESI +): m / z = 400, 402 [M + H] + E pvl XVII 4- [(3-chloro-4-fluorophenyl) amino] -6- ( { Trans - A - [(vi-nylsulf onyl) amino] -cyclohex-1-yl}. Amino) - pyrimido- [5, 4-d] pyrimidine A 388 mg of 4 - [(3-c 1 oro-4-f 1 uoropheni 1) -amino] -6- [(trans-4-aminocyclohex-1-yl) amino] ] -piri -mi do [5, 4-d] pir imi di na in 25 ml of tetrahydrofuran is added 0.38 ml of diisopropylethylamine. The mixture is cooled to -55 ° C, under atmosphere} of nitrogen, in a bath of a c a t on a / h i e 1 or dry. Then a solution of 0.13 ml of chloride of 1-chloroacetate in 5 ml of tetrahydrofuran is added dropwise, and stirring is continued. . g for an additional 1.5 hours at -55 ° C. The reaction mixture is quenched with a mixture of 10 ml of IN hydrochloric acid and 10 ml of saturated sodium chloride solution, and a small amount of ethyl acetate is mixed. The organic phase is filtered through 8.5 g of ExtrXlut (E. Merck, Darmstadt) and eluted with 100 ml of methylene chloride / methanol (9: 1). The filtrate is concentrated by evaporation, leaving a yellow solid. Yield: 216 mg (45% of theory) melting point: 226-230 ° C (decomposition) Mass spectrum (El): m / z = 477, 479 [M] + Example XVI I I. { R) - A - [(1-f-enylethyl) amino] -6-met lsulfinyl-pyri-do [5], -d] pyrimidine and (R) - A - [(1-f-enylethyl) amino] -6-methylsulfonyl-pyriphyndi [5, -d] pyrimidine A 17.40 g of (S) -4- [(1- f eniletil) aminc. I-pyridine [5, 4-d] pyrimidine in 180 ml of methylene chloride are added at room temperature, in portions and with stirring, 28.80 g of 3-c-1 acid. or op e rbe nzoi co (content: 70%). The reaction mixture is then stirred during approximately one hour at room temperature. The resulting white precipitate is filtered off, and the filtrate is washed with sodium hydrogen carbonate solution, dried over magnesium sulfate and concentrated by evaporation. The oily, orange-colored residue is a mixture of sulfone and sulfoxide (approximately 85:15 according to X-NMR). Rf value: 0.47 (silica gel, cyclohexane / ethyl acetate / methanol = 5: 4: 1) Mass spectrum (ESI +): m / z = 352 [M + Na] + (sulfone), 336 [M + Na] + (sulfoxide) And XIX. { R) - A - [(1-Phenylethyl) amino] -6-methylthio-pyrimido [5, 4-d] pyrimidine A 13.00 g of 4-chloro-6-methylthio-p irimido [5, 4-d] Pyrimidine in 100 ml of dimethylformamide are added 10.7 ml 'of diisopropylethylamine and 9.4 ml of D (+!) - 1-phenylethylamine. The mixture is stirred for four hours at room temperature. The reaction mixture is poured into 200 ml of water for its preparation. The aqueous phase is extracted with methylene chloride, the combined organic phases are dried over magnesium sulfate and concentrated by evaporation. The oily, dark brown residue is taken up in ethyl acetate and extracted with 10% citric acid. The organic phase is dried over magnesium sulphate and concentrated by evaporation, leaving a reddish-brown oil. Yield: 17.40 g (96% of theory) Rf value: 0.63 (silica gel, cyclohexane / ethyl acetate / methanol = 5: 4: 1) Mass spectrum (ESI +): m / z = 298 [M + H ] + E j lo lo XX trans-1- [(terbutyloxycarbonyl) amino] - A - [(2-hydroxy-2-met? L-prop-l-yl) amino] -cydohexane Prepared by the tran reaction -1- [(tert.butyloxycarbonyl) amino] -4-amino-cyclohexaryl with 2,2-dimethyl-oxirane in ethanol a closed vessel is used followed by purification and by chromatography of the product mixture without purification on silica gel. . Rf: 0.06 (silica gel, ethyl acetate / methane, or 1 = 9: 1) Mass spectrum (ESI +): m / z = 287 [M + H] + Preparation of the final products: ___ ^ .____ v ._ ,, -., _, .-. »__ _ -.______« _, ...._ .. _ __._, E j emp lo 1 4- [(3-chloro-4-fluoro-phenyl) amino] - 6 -. { [1- (carboxymethyl) -piperidin-4-yl] amino} -pyrim do [5, 4-d] pyrimidine to A a suspension of 400 mg of 4- [(3-chloro-4-f luoro-f-enyl) amino] -6- (. {1- 1- [( methoxycarbonyl) -methyl] -piperidin-4-yl.}. amino) -pyrimido [5, 4-d] pyrimidine in 5.0 ml of tetrahydrofuran are added, 2.0 ml of sodium hydroxide solution IN. The resulting clear solution is stirred for about three more hours, at room temperature. The reaction solution is then neutralized with IN hydrochloric acid and concentrated by evaporation using a rotary evaporator until the product begins to crystallize out. The yellow precipitate is filtered off, washed with water and with diethyl ether and dried under vacuum at 60 ° G. Yield: 365 mg (96% of theory) melting point: 155 ° C (decomposition) Mass spectrum (El): m / z = 431, 433 [M] + The following compounds are obtained analogously to Example 1: jj ^^^^^^^^^ ¿¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^^^^^ ^^^^ wg ^^^ (1) 4 - [(3-chloro-4-fluoro-phenyl) amino] -6-. { [1- (2-carboxyethyl) -piperidin-4-? L] amino} -pyrimido- [5, -d] pyrimidine melting point: 217-225 ° C Mass spectrum (El): m / z = 445, 447 [M] + (2) 4 - [(3-chloro-4- fluoro-phenyl) amino |] -6-. { [1- (3-carboxypropyl) -piperidin-4-yl] amino} -pyrimido [5, 4-d] pyrimidine melting point: 145-165 ° C Mass spectrum (El): m / z = 459, 461 [M] + (3) 4 - [(3-chloro-4- fluoro-phenyl) amino]] - 6 - ( { trans-A- [N- (carboxymethyl) -N-methylamino] -cyclohex-1-yl} amino) -pyrimido- [5,4-d] -pipmidine melting point: 220-228 ° C Mass spectrum (ESI +): m / z = 460, 462 [M + H] + (4) 4- [(3-chloro-4-fluoro-phenyl) amino] -6- ( { Trans-A- [N- (2-carboxyethyl) -N-methylamino] -cyclo-hex-l-yl}. Amino) -pyrimido [5, 4-d] -pyrimidine point melting: 202-205 ° C Mass spectrum (ESI +): m / z = 474, 476 [M + H] + (5) 4 - [(3-chloro-4-fluoro-phenyl) amine] -6- ( { trans-A- [N- (3-carboxypropyl) -N-methylamino] -cyclohex-l-yl) amino) -pyrimido [5, 4-d] pyrimidine melting point: 217-221 ° C mass (ESI +): m / z = 488, 490 [M + H] + ^^ & | J? tt ?? gßág¡ ^^^^^^^^^^^^^ gí ^^^^^^^^^^^^^^ (6) A - [(3-Chloro-4-fluoro-phenyl) amino] -6- [4 - (carboxymethyl) -piperazin-1-yl] -pyrimido [5, 4-d] -pyrimidine melting point: 240 ° C ( decomposition) i Mass spectrum (El): m / z = 417, 419 [M] (7) 4- [(3-chloro-4-fluoro-phenyl) amino] -6- [4 - (2-carboxyethyl) -piperazin-1-yl] -pyrimido [5, 4-d] pyrimidine melting point: 111-145 ° C Mass spectrum (El): m / z = 431, 433 [M] + (8) 4- [(3-chloro-4-fluoro-phenyl) amino] - 6 -. { 4 - [1- (2-carboxyethyl) -piperidin-4-yl] -piperazin-1-yl} -pyrimidine [5, 4-d] pyrimidine melting point: 213 ° C (decomposition) Mass spectrum (El): m / z = 514, 516 [M] + (9) 4- [(3-chloro-4 -fluoro-phenyl) amino] -6-. { 2 - [1- (Carboxymethyl) -piperidin-4-yl] ethylamino} -pyrimidine [5, 4-d] pyrimidine melting point: 246-249 ° C (decomposition) Mass spectrum (El): m / z = 459, 461 [M] + (10) 4 - [(3-chloro -4-fluoro-phenyl) amino] -6- [2- (4-carboxypiperidin-1-yl) ethylamino] -pyrimido- [5, -d] pyrimidine melting point: 190 ° C (decomposition) Mass spectrum (El): m / z = 445, 447 [M] + (11) 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- [4- [N- (2-carboxyethyl) -N -methylamino] -piperidin-1-y1] -pyrimido [5, 4-d] pir imi di melting point: 139-165 ° C (decomposition) Mass spectrum (El): m / z = 459 , 461 [M] + (12) 4- [(3-chloro-4-fluoro-phenyl) amino] -6-. { 3- [4- (2-carboxyethyl) -piperidin-1-yl] -pyrrolidin-1-i 1} - pir imi do [5, 4 - d] pir imidi na value of Rf: 0.63 (silica gel, chloride of me ti 1 e no / me tano 1 / trieti 1 ami na = 2: 1: 0.1) Mass spectrum (El): m / z = 499, 501 [M] + (13) 4- [(3-chloro-4-fluoro-phenyl) amino] -6-. { 2 - [4- (Carboxymethyl) -piperazin-1-yl] ethylamino} -pyrimidine [5,4-d] pyrimidine melting point: 240-242 ° C (decomposition) Mass spectrum (ESI "): m / z = 459, 461 [MH] - (14) 4- [(3- Chloro-4-fluorophenyl) amino] -6- (4-amino-4-carboxy-piperidin-1-yl) -pyrimido [5, 4 -d] pyrimidine melting point: 277-282 ° C Mass spectrum (The ): m / z = 417, 419 [M] + (15) 4- [(3-chloro-4-fluorophenyl) amino] -6- [4 - (N-carboxymethyl-N-methylamino) -piperidin-1- il] -piri-mi do [5, 4 - d] pir imi di na 4_A_ Rf value: 0.05 (silica gel, me 111 chloride and no / me ta no 1 / s or 1 aqueous ammonia concentrate = 90: 10: 0.1) Mass spectrum (ESI "): m / z = 444, 446 [MH] "(16) 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- (4 -. {[[(2-carboxyethyl) -amino] methyl]. piperidin-1-yl) -pyrimido [5, 4-d] pyrimidine melting point: 209-214 ° C Mass spectrum (ESI "): m / z = 458, 460 [MH]" (17) 4 - [ (3-Chloro-4-fluoro-phenyl) -amino] -6- (4 - { [(Carboxymethyl) -amino] methyl.}. -piperidin-1-yl) -pyrimido [5, 4-d] pyro imi di na melting point: 226-235 ° C Mass spectrum (ESI "): m / z = 444, 446 [MH]" (18) 4 - [(3-chloro- 4 - f luor of eni 1 ) amino1] -6- ( { trans - A - [N, N-bis- (carboxymethyl) amino] -cyclohe | jl-yl} amino) -pyrimido [5, 4-d] pyrimidine melting point : 245 X (decomposition) Mass spectrum (ESI): m / z = 502, 504 [MH] "(19) 4 - [(3-chloro-4-f luorofenyl) amino] -6- (4 . { [N, N-bis- (2-carboxyethyl) amino] methyl} -piperidinyl-il) -pyrimido [5, 4-d] pyrimidine melting point: 160-169 ° C Mass spectrum (ESI "): m / z = 530, 532 [MH]" (20) 4- [( 3-chloro-4-fluorophenyl) amino] -6- (3 - { [N, N-bis- (2-carboxyethyl) amino] methyl.}. -pipepdin-1-yl) -pyrimido [5, 4-d] pyrimidine Rf value: 0.79 (TLC plate prepared by reverse phase (E. Merck), acet on itri 1 o / water / trifluoroacetic acid = 90: 10: 1) Mass spectrum (ESI "): m / z = 530, 532 [MH] "(21) 4- [(3-chloro-4-fluorophenyl) amino] -6- (4-i { [N, N-bis (carboxymethyl) amino] methyl] ) -piperidin-1- i 1) - pir imi do [5, 4 - d] pir imidi na Rf value: 0.85 (TLC plate prepared by reverse phase (E. Merck), acet on itri 1 o / a gua / Trifluoroacetic acid = 90: 10: 1) Mass spectrum (ESI "): m / z = 502, 504 [MH]" (22) 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- (N- { Trans-4- f N ', N' -bis (carboxymethyl) amino] -cyclohex-1-yl.} - N -methylamino) -pyrimido [5, 4-d] pyrim idina value of R: 0.33 (TLC plate prepared by reverse phase (E. Merck), methanol / 5% aqueous solution of sodium chloride = 8: 2) Mass spectrum (ESI "): m / z = 516, 518 [MH]" (23) 4- [(3-chloro-4 -fluorophenyl) amino] -6- (N- { trans - A - [(carboxymethyl) amino] -cyclohex-1-yl.} - N -methylamino) -pyrimido [5, 4-d] -pyrimidine Rf value: 0.30 (TLC plate prepared by reverse phase (E. Merck), methanol / aqueous solution at | 5% sodium chloride = 8: 2) Mass spectrum (ESI "): m / z = 558, 560 [MH] "(24) 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- (3. {[[(2-carboxyethyl) amino] methyl.}. -piperidin-1-yl) -pyrimido [5, 4-d] pir imi di melting point: 173-179 ° C Mass spectrum (ESI "): m / z = 558, 560 [MH]" (25) 4 - [(3- chloro-4-f luorofenyl) amino] -6- (3- {[[N, N-bis (carboxymethyl) amino] methyl} - piperidin-1.} yl) -pyrimido [5.4- d] pyrimidine Rf value: 0.82 (TLC plate prepared by reversed phase (E. Merck), acet oni tri 1 o / a trifluoroacetic acid = 90: 10: 1) Mass spectrum (ESI "): m / z = 502, 504 [MH] "(26) 4- [(3-chloro-4-fluorophenyl) amino] -6- (3 - { [(carboxymethyl) -amino] methyl.}. -p? peridin-1-yl) -pyrimido [5,4-d] pyrimidine value of Rf: 0.82 (TLC plate prepared by reversed phase (E. Merck), acet oni tri 1 o / a gua / á ci do tr i f 1 u o r o a c e t i co = 90: 10: 1) Mass spectrum (ESI "): m / z = 444, 446 [M-H]" & g ^^^ j ^^ K ^^^ and &? SI ^^ ét &? g ^ á ^^^^ k (27) 4 - [(3-chloro-4-fluorofen? l) amino] - 6- ( { Trans - A - [(carboxymethyl) amino] -cyclohex-1-yl.}. -amino) -pyrimido [5, 4-d] pyrimidine melting point: 201-205 ° C (decomposition) Mass spectrum (ESI "): m / z = 444, 446 [MH]" (28) 4- [(3-chloro-4-fluorophenyl) amino] -6- (N- { Trans - A - [ N '- (carboxymethyl) -N' -methylamino] -cyclo-hex-l-yl.} - N -methylamino) -pyrimido [5, 4-d] pyrimidine melting point: 200 ° C (decomposition) Spectrum of mass (ESI "): m / z = 472, 474 [MH]" (29) 4 - [(3-chloro-4-fluorophenyl) amino] -6-. { 4- [(2-carboxy-piperidin-1-yl) methyl] -piperidm-1-yl} -p i r imi d o [5, 4 - d] p i r imi d i n a (is carried out with potassium butoxide as the base). melting point: 225-237 ° C (decomposition) Mass spectrum (ESI "): m / z = 498, 500 [MH]" (30) 4- [(3-chloro-4-fluorophenyl) amino] -6 -. { 4-methyl-4- [(2-carboxyethyl) amino] -piperidin-1-yl} - | p r imed [5, 4 - d] p i r imi din. i melting point: 157-160 ° C Mass spectrum (ESI "): m / z = 458, 460 [MH]" (31) 4- [(3-chloro-4-fluorophenyl) amino] -6 { . - (4 - { [4- (carboxymethyl) -piperazin-1-yl] methyl.}. -piperi? Lin-l-yl) -pyrimido [5,4-d] pyrimidine ^ Aa ^ j ^ & Rf value: 0.60 (TLC plate prepared by reversed phase (E. Merck), acet oni tri 1 o / a trifluoroacetic acid = 90: 10: 1) Mass spectrum (ESI "): m / z = 513, 515 [MH] "(32) 4- [(3-chloro-4-fluorophenyl) amino] -6. { 4 -met? L-4- [(carboxymethyl) amino] -piperidin-1-? L} -pyrimido [5, 4-d] pyrimidine. melting point: 160 ° C (decomposition) Mass spectrum (ESI "): m / z = 444, 446 [M-H]" (33) 4- [(3-chloro-4-fluorophenyl) amino] -6. { 4 - [(2-carboxy-pyrrolidin-1-yl) methyl] -piper? Dm-1-yl} -p i rimido [5, 4-d] p i r imi di na (carried out with potassium butoxide as a base). melting point: 140-162 ° C (decomposition) Mass spectrum (ESI "): m / z = 484, 486 [M-H]" E j lo lo 2 A - [(3-chloro-4-fluoro-phenyl) amino] -6- (. {1 - [(ethoxycarbonyl) methyl] -piperidin-4-yl} amino) -pyrimido [ 5, 4-d] pyrimidine A 676 mg of a mixture of 4- [(3-chloro-4-f-luoro-phenyl) -amino] -6-methylsulf-mil-pyrimido [5; 4-d] pyrimidine and 4- [(3-chloro-4-fluoro-phen? L) aminq] -6-me ti 1 su 1 foni 1-pir imi do - [5, 4-d] pir imi di na In 14J ml of dioxane and 2 ml of ethanol, 778 mg of di-1-ori-4-ami no-1 - [(ethoxycarb on i 1) me ti 1] -piperidine are added. Then 0.55 ml of triethylamine and 829 mg of potassium carbonate are added, and the reaction mixture is refluxed for about seven hours. The reaction mixture is then concentrated by evaporation and the residue is stirred with ice water, filtered off with suction, washed with water and dried. The yellowish-brown unpurified product is purified by chromatography through a column of silica gel with methylene chloride / ethanol (95: 5). Yield: 526 mg (57% of theory) melting point: 136-38 ° CI Mass spectrum (El): m / z = 459, 461 [M] + The following compounds are obtained analogously to Example 2: ( 1) 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- ( { 1- [(methoxycarbonyl) methyl] -piperidin-4-yl} amino) -pyrimid [5 , 4 - d] pir imi di na melting point: 162-164 ° C Mass spectrum (El): m / z = 445, 447 [M] + (2) 4- [(3-chloro-4-fluoro -phenyl) aminq] -6- ( { 1- [(propyloxycarbonyl) methyl] -piperidin-4-yl.}. ami-no) -pyrimido [5,4-d] pyrimidine mp: 135-137 ° C Mass spectrum (El): m / z = 473, 475 [M] + (3) 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- (. {1- 1- [( isopropyloxycarbonyl) methyl] -piperidin-4-yl-amino) -pyrimido [5,4-d] pyrimidine melting point: 175-177 ° C Mass spectrum (El): m / z = 473, 475 [M] + (4 ) 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- (. {1- [(cyclohexyloxycarbonyl) methyl] -piper? Din-4-11.} Amy no) -pyrimido [5 , 4-d] pyrimidine. melting point: 184-186 ° C Mass spectrum (El): m / z = 513, 515 [M] + (5) 4- [(3-chloro-4-fluoro-phenol) amino] -6 - ( { 1- [2- (methoxycarbonyl) ethyl] -piperidin-4-yl} amino) -pyrimido [5, 4-d] pyrimidine. melting point: 136-137 ° C Mass spectrum (ESI +): m / z = 460, 462 [M + H] + (6) 4 - [(3-chloro-4-fluoro-phenyl) amino] -6 - ( { 1- [3- (methoxycarbonyl) propyl] -p? Peridin-4-i 1.}. Ami no) -pyrimido [5, 4-d] pyrimidine m melting point: 135 -137 ° C Mass spectrum (El): m / z = 473, 475 [M] + (7) 4 - [(3-chloro-4-fluoro-phen? L) amincj] -6- [(trans 4- { N- [(methoxycarbonyl) methyl] -N-methylamino.} -cic 1 oh ex-1-i 1) ami no] -pyrimido [5, 4-d] pyrim imi di na ^ * ^^ ________________________________ melting point: 131-134 ° C Mass spectrum (El): m / z = 473, 475 [M] + (8) 4 - [(3-chloro-4-fluoro-phenol ) amino] -6 [(trans-4- { N- [2- (methoxycarbonyl) ethyl] -N-methylamine.} - cyclohex-1-yl) amino] -pyrimido [5, 4-d ] pyrimidine melting point: 126-128 ° C Mass spectrum (El): m / z = 487, 489 [M] + 9) 4 - [(3-chloro-4-fluoro-phenyl) amino] -6 [ (trans-A - { N - [3- (methoxycarbonyl) propyl] -N-methylamino.} - cyclohex-1-yl) amino] -pyrimido [5, 4-d] pyrimidine mp: 99 -102 ° C Mass spectrum (ESI +): m / z = 502, 504 [M + H] + (10) 4- [3-chloro-4-fluoro-phenyl) amino] -6 [4 - [( ethoxycarbonyl) -methyl] -piperazin-1-yl] -pyrimido [5, 4-d] pyrimidine melting point: 179-182 ° C (12) 4- [(3-chloro-4-fluoro-phenyl) amino] -6- (4- { 1- [2- (ethoxycarbonyl) ethyl] -piperidin-4-yl) -piperazm-1- ?) -pyrimido- [5, 4-d] pyrimidine Rf value: 0.51 (silica gel, methylene chloride / methanol = 9: 1) Mass spectrum (El): m / z = 542, 544 [M ] + (13) 4- [(3-chloro-4-fluoro-phenyl) amiho] -6- (2 - { 1 - [(ethoxycarbonyl) methyl] -piperidin-4-yl.}. Etalamino) - pyrimido [5, 4-d] pyrimidine melting point: 128-130 ° C l Mass spectrum (El): m / z = 487, 489 [M] + (14) 4 - [(3-chloro-4- fluoro-phenol) amino] -6-. { 2 - [4- (Ethoxycarbonyl) -piperidin-1-yl] ethylamino} 1 pyramid [5,4-d] pyrimidine melting point: 137-139 ° C Mass spectrum (El): m / z = 473, 475 [M] + (15) 4- [(3-chloro- 4-fluoro-phenyl) amiho] -6- (4 - { N - [2- (methoxycarbonyl) ethyl] -N-methylamino}. -pipe-pdin-1-yl) -p-rimido- [5 , 4-d] pyrimidine Rf value: 0.15 (silica gel, ether) of petr or 1 eo / ethyl acetate / methanol = 5: 5: 1) Mass spectrum (El): m / z = 473, 475 [M] + I (16) 4- [(3-chloro-4-fluoro-phenol) aminq] -6- (3- {4- [2- (methoxycarbonyl) ethyl] -piperidin-1] -il.}., -pirro 1 i di n - 1 - i 1) - pyrimidi - [5, 4 - d] pir imi di na i ** ^^^^^ * ^^^^^^^^^^^^^^^ melting point: 166-168 ° C Mass spectrum (El): m / z = 513, 515 [M] + (17) 4- [(3-bromophenyl) amino] -6- ((1- [(methoxycarbonyl) ) methyl] -piperidin-4-yl.}. amino) -pyrimido [5, 4-d] pyrimidi melting point: 144 ° C Mass spectrum (ESI +): m / z = 472, 474 [M + H] + (18) 4- [(3-bromophenyl) amino] -6- (3- {N [(methoxycarbonyl) methyl] -N-methylamino} propylaminopyrimid [ 5, 4-d] pir imi di na Rf value: 0.35 (silica gel, cyclohexane / ethyl acetate / methanol = 5: 4: 1) Mass spectrum (ESI +): m / z = 474, 476 [M + H] + (19) 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- ( { N - [(methoxycarbonyl) methyl] -N-methylamino} methyl) -piperidine -1-? L] -pyrimido- [5, 4-d] pyrimidine Rf value: 0.88 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia solution = 90: 10: 0.1). El): m / z = 473, 475 [M] + ¡(20) 4- [(3-chloro-4-fluorophenyl) amino] -6¡- (4 - { [2- (methoxycarbonyl) -piperidin -1-il] methyl.}. -piper idin-1-yl) -pyrimido [5, 4-d] -pyrimidine Rf value: 0.73 (silica gel, ether! petroleum / ethyl acetate / methanol = 10: 10: 1) * £. ? j.l.r & ~. * rY-ix, ¿atifari. .sa < ttÜ ?.

ESI mass spectrum m / 514, 516 [M + H (21) 4- [(3-Chloro-4-fluorophenyl) amino] -6- (4 { [2- (methoxycarbonyl) -pyrrolidin-1-yl] methyl.}. - p? Peridin-1-yl ) -pyrimido [5, 4-d] -pyrimidine melting point: 151-154 ° C Mass spectrum (ESI +): m / z = 500, 502 [M + H] + (22) 4- [(3- chloro-4-fluorophenyl) amino] -6- [4 (. {4- [(ethoxycarbonyl) methyl] -piperazin-1-yl] methyl] -piperidin-1-yl] -pyrimido- [5, 4 -d] pyrimidine melting point: 145-149 ° C Mass spectrum (ESI +): m / z = 543, 545 [M + H] + (23) 4 - [(3-chlorophenyl) amino] -6X. { l [(methoxycarbonyl) methyl] -pipepdin-4-yl.}. amino) -pyrimido [5, 4-d] pyrim imi mp melting point: 129 ° C Mass spectrum (El): m / z = 427, 429 [M] + (24) 4- [(3-methylphenyl) ammo] -6- (. {1 l [(methoxycarbonyl) methyl] -piperidin-4-yl} amino) -pyr imi do [5, 4 - d] pir imi di melting point: 164 ° C Mass spectrum (El): m / z = 407 [M] + (25) (_.) - 4- [(l- phenylethyl) amino] -6- ( { 1 - [(methoxycarbonyl) -methyl] -piperidin-4-yl} amino) -pyrimido [5, 4 - d] p i r i mi d i n a Rf value: 0.39 (silica gel, ethyl acetate / methanol = 95: 5) Mass spectrum (El): m / z = 421 [M] + (26) 4- [(4-amino-3, 5 -dichlorophenyl) amino] -6 - ( { 1- [(methoxycarbonyl) methyl] -piperidin-4-yl} aminp pyrimido [5, 4-d] pyrimidine melting point: 218 ° C Mass spectrum ( El): m / z = 476, 478, 480 [M] (27) 4- [(4-amino-3,5-dibromophenyl) amino] -6 - (. {1- [(methoxycarbonyl) methyl] - piperidin-4-yl.}. amincp) -pyrimido [5, 4-d] pyrimidine melting point: 167 ° C Mass spectrum (El): m / z = 564, 566, 568 [M] + (28) 4- [(indol-5-yl) amino] -6- ( { L- [(methoxycarbonyl) methyl] -piperidin-4-yl} amino) -pyrimido [5, 4-d] pyrimidine point melting: 167 ° C Mass spectrum (El): m / z = 432 [M] + (29) 4- [(3-chloro-4-fluoro-phenyl) amino] -6- { [trans-4 - (6,6-dimethyl-2-oxo-morpholin-4-yl) -cyclohex-1-yl] amino.} - pyrimido- [5, -d] pyrimidine Rf value: 0.66 (silica gel, acetate; ethyl / methanol) Mass spectrum (ESI "): m / z = 498, 500 [MH]" E j lo lo 3 4- [(3-chloro-4-fluoro-phenyl) amino] -6- (2 - (4- [(ethoxycarbonyl) methyl] -piperaz? Nl-yl.}. Ethylamino-pyrimidine [5, 4-d] pyrimidine A 2.01 g of 4 - [(3-c 1 oro-4-f 1 uo ro-phenyl) amino] -6- [2- (piperazin-1-yl) ethylammo] -pyrimido [5,4-d] pyrimidine in 50 ml of pyridine are added 2.08 ml of triethylamine and 0.61 ml of bromoacetate The reaction mixture is stirred for two hours at room temperature, after the reaction mixture is concentrated by evaporation, water is added, and the mixture is extracted with methylene chloride, the combined organic phases are dried over magnesium sulfate. and concentrated by evaporation The yellow unpurified product is purified by chromatography through a column of aluminum oxide (activity III) with methylene chloride / ethanol (99: 1) Yield: 1.97 g (81% of theoretical) melting point: 128-129 ° C Mass spectrum (ESI +): m / z = 489 [M + H] + The following compounds are obtained analogously to Example 3: (1) 4- [(3-chloro-4-fluorophenyl) amino] -6- (4 - . { N - [(ethoxycarbonyl) methyl] -N-methylamino} -piperid :. n-1-yl) -pyrimido [5,4-d] pyrimidine Rf value: 0.63 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia solution = 90: 10: 0.1) Mass spectrum (El) : m / z = 473, 475 [M] '(2) 4 - [(3-chloro-4-fluorophenyl) amino] -X [4- ( { [2- (methoxycarbonyl) -ethyl] amino.} methyl) -piperidin-1-y1] -pyrimido [5, 4-d] pir imi di na (the reaction is carried out with methyl 3 -br oropropy) value of Rf: 0.57 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia solution = 90: 10: 0.1) Mass spectrum (El): m / z = 473, 475 [M] + (3) A - [(3 -chloro-4-fluorophenyl) amino] -6- [4 - (. {[[(methoxycarbonyl) ethyl] aminojmethyl) -piperidin-1-yl] -pyrimido [5, 4-d] pyrimidine Rf value: 0.66 (gel silica, methylene chloride / methanol / concentrated ammonia aqueous solution = 90: 10: 0.1) Mass spectrum (El): m / z = 459, 461 [M] + (4) 4- [(3-chloro- 4-fluorophenyl) amino] -6- [(trans-4- { N, N-bis [(ethoxycarbonyl) methyl] amino) - I c i c 1 ohe x - 1 - i 1) ami no] -p i rimido [5, 4 - d] p i r imi di na | (the ^^^^ á ^^^^^^ t ^^^^ ^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ^^^ reaction is carried out in acetonitrile i with di is op r op i 1 -eti 1 amine as auxiliary base) melting point: 155-157 ° C Mass spectrum (El): m / z = 559, 561 [M] + (5) 4- [(3-chloro-4-fluorophenyl) amino] -6- [(trans-4- (N, N-bis [(methoxycarbonylmethyl] amino.) 1-cyclohex-1-yl) amino] -pyrimido [5, 4-d] pyrimidine (the reaction is carried out in acetonitrile with di isop r op i 1 -eti 1 amine as auxiliary base) melting point: 181-184 ° C Mass spectrum (ESI +): m / z = 532, 534 [M + H] + (6) 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- ( { [(Ethoxycarbonyl) -methyl) ] amino) methyl) -piperidin-1-y1] - pyrimido [5, 4-d] pi r imidine (the reaction is carried out in acetonitrile with diisopropyl-ethyl amine as an auxiliary base) Rf value: 0.75 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia solution = 90: 10: 1) Mass spectrum (El): m / z = 473, 475 [M] + (7) 4- [(3-chloro-4-fluorophenyl) amino] -6- [4 - (. { N, N-bis [(ethoxycarbonyl) ethyl] amino} methyl) -piperidin-1-yl] -pyrimido [5, 4-d] -pyrimidine the reaction is carried out in acetonitrile with diis op r op i 1 -eti 1 amine as auxiliary base) Rf value: 0.65 ( silica gel, methylene chloride / methanol = 95: 5) Mass spectrum (ESI +): m / z = 560, 562 [M + H] + (8) 4 - [(3-chloro-4-fluorophenyl) amino ] -6- [4- ( { N, N-bis [(methoxycarbonyl) methyl] amino.} Methyl) -p ip eri di n- 1 -i 1] -pyrimido [5, 4-d ] - pir imi di na I (the reaction is carried out in acetonitrile with diis op r op i 1 -eti 1 amine as an auxiliary base) Rf value: 0.81 (silica gel, methylene chloride / methanol / aqueous solution) of concentrated ammonia = 90: 10: 0.1) Mass spectrum (ESI +): m / z = 532, 534 [M + H] + ¡(9) 4- [(3-chloro-4-fluorophenyl) amino] -6 - [3 I ( { N, N-bis [(methoxycarbonyl) methyl] amino.} Methyl) -pipe ri di n-1-i 1] -pyrimido [5, 4 -d] -pyrimidine (Reaction is carried out in acetonitrile with diisopropyl-ethylamine as the base auxiliary) Rf value: 0.83 (silica gel, chlorine of me 111 ene / me tano 1 / s or 1 aqueous ammonia concentrate = 90: 10: 0.1) Mass spectrum (ESI +): m / z = 532, 534 [M + H] + (10) 4 - [(3-chloro-4-fluorophen? L) amino] -6- [(tra__s-4-. { [(methoxycarbonyl) methyl] amino} -cyclohex- 1 - i 1) ami no] - p i rimido [5, 4 -d] p i r imi di na (the reaction _ ^ ^ G * ^^^^^^^^^ fe ^^ is carried out in acetonitrile with diisopropyl ethylamine as auxiliary base) melting point: 141-143 ° C Mass spectrum (El): m / z = 459, 461 [M] + (11) 4- [(3-chloro-4-f luorofenyl) amino] -6- [N- [trans-A-. { [(methoxycarbonyl) methyl] amino} -cyclohe ^ -li 1) - N -me ti 1 ami no] -pyrimido [5, 4 - d] pir Imi di na '(the reaction is carried out in acetonitrile with di is op r op i 1 - eti 1 amine as auxiliary base) melting point: 169.5 - 171.5 ° C Mass spectrum (ESI +): m / z = 474, 476 [M + H] + (12) A - [(3-chloro-4- fluorophenyl) amino] -6- [N- (trans-4- { N ', N' -bis [(methoxycarbonyl) methyl] aminocyclohex-1-yl) -N-methylamino] -pyrimido [5, 4 - d] pyrimidine (for the method see Example 3 (11)) melting point: 162-164 ° C Mass spectrum (ESI +): m / z = 546, 548 [M + H] + (13) 4- [ (3-Chloro-4-fluorophenyl) amino] -q - [3 - (. {[[(Methoxycarbonyl) methyl] amino} methyl) -piperidin-1-yl] -pyrimido [5, 4 - d] pir imidi na (the reaction is carried out in acetonitrile with di isop r op i 1 -eti 1 amine as an auxiliary base). , -.___ I; Rf value: 0.76 (silica gel, methylene chloride / methanol / aqueous amorphous solution, concentrated iac = 90: 10: 0.1) Mass spectrum (ESI +): m / z = 460, 462 [M + H] + (14) - [(3-chloro-4-f luorofenyl) amino] -6- [N- (tra.ns-4- { N '- [(methoxycarbonyl) methyl] -N'-methylamino} cyclohex-l-yl) -N-methyl-amino] -pyrimido [5, 4-d] pyrimidine (the reaction is carried out in acetonitrile with di is op r op i 1 -eti 1 ami na as auxiliary base). melting point: 137-139.5 ° C Mass spectrum (ESI +): m / z = 488, 490 [M + H] + (15) 4- [(3-chloro-4-fluorophenyl) amino] -6-. { TO a a e o Mass spectrum (ESI +): m / z = 460, 462 [M + H] + (16) 4 - [(3-bromophenyl) amino] -6- (1- [1, 1-bis (methoxycarbonyl) -methyl) ] -piper? din-4-yl.}. amino) -pyrimido [5, 4-d] pir imi di na (the reaction is carried out with br omoma 1 ona to dimethyl in acet on itri 1 or, in the presence of di is op r op 11-ethylamine as an auxiliary base). melting point: 158-160 ° C Mass spectrum (ESI +): m / z = 530, 532 [M + H] + (17) 4- [(3-bromofenyl) amino] -6- ( { 1 [(methoxycarbon? l) methyl] -piper? din-3-yl} amino) -p i rimido [5, 4-d] p i r imi di na (the reaction was carried out in acetonitrile with di i s or op r i 1 - e t i 1 ami na Xomo auxiliary base). melting point: 113 ° C Mass spectrum (ESI +): m / z = 472, 474 [M + H] + (18) 4- [(3-chloro-4-fluorophenyl) amino] -6- (1- [1,1-bis (methoxycarbonyl) methyl] -piperidin-4-yl]. -amino) -pyrimido [5,4-d] pyrimidine (the reaction is carried out with br omoma 1 ona to dimethyl in acetonitrile , in the presence of di is op r op i 1 - eti 1 na as auxiliary base). melting point: 192-193 ° C Mass spectrum (ESI +): m / z = 504, 506 [M + H (19) 4 - [(3-chloro-4-f luoro-f-enyl) amin]] - 6- ( { 1- [(methoxycarbonyl) methyl] -piperidin-3-yl.}. Amincj.) -pyrimido [5, 4-d] pyrimidine (The reaction was carried out in acetonitrile in the presence of diisopropylethylamine) .

Rf: 0.49 (silica gel, ethyl acetate / methanol = 9: 1) Mass spectrum (ESI +): m / z = 446, 448 [M + H] + (20) 4- [(3-chloro- 4-fluoro-phenyl) amino] -6 - ( { 1- [(phenoloxycarbonyl) methyl] -piperidin-3-yl.] Am: no) -pyrimido [5, 4-d] pyreidimide na (The reaction was carried out | in phenyl bromoacetate in acetonitrile in the presence of diisopropylethylamine). Melting point: 166 ° C Mass spectrum (ESI +): m / z = 508, 510 [M + H] + (21) 4- [(3-chloro-4-fluoro-phenyl) amino] -6 ( { 1- [(benzyloxycarbonyl) methyl] -piperidin-3-yl.}. Ami-n o) -pyrimido [5, 4-d] pi r imidine (The reaction was carried out with benzyl bromoacetate. in acetonitrile in the presence of diisopropylethylamine). Melting point: 145 ° C Mass spectrum (ESI "): m / z = 520, 522 [M-H]" (22) 4- [(3-chloro-4-fluoro-phenyl) amino] -6 ( { 1- [(indan-5-yl-oxycarbonyl) methyl] -piperidin-3-yl.}. Amino) -pyrimido [5,4-d] pyrimidine (The reaction was carried out with bromoacetate of indan-5-yl in acetonitrilol in the presence of diisopropylethylamine). "- - • * • * - < > -Fusion point: 133 ° C Mass spectrum (El): m / z = 547, 549 [M] + (23) 4- [(3-chloro 4-fluoro-phenyl) amine] - 6 - ( { 1- [(tertbutyloxycarbonyl) methyl] -piperidin-3-yl} amino) -pyrimido [5, 4-d] pyrimidine (The reaction was carried out with tert.-butyl bromoacetate in acetonitrile! in the presence of diisopropylethylamine.) Melting point: 146 ° C Mass spectrum (ESI +): m / z = 488, 490 [M + H] + Example 4 4- [(3-Chloro-4-fluoro-phenyl) amino] -6- (2 -. {4 - [(diethoxy-fluo-yl) -methyl] -piperazin-1-yl}. ethylamino) -pyrimido [5, 4-d] pyrimidine A suspension of 500 mg of 4 - [(3-c 1 oro-4-f-1-or -phenyl) amino is heated at 95-100 ° C with stirring. ] -6- [2- (piperazin-1-yl) ethylamino] -pyrimido [5, 4-d] pyrazimine in 15 ml of dioxane, until the solid has substantially dissolved. Subsequently, 100 μl of 37% formaldehyde solution and then 190 μl of diethylphosphite are initially added in hot. The reaction mixture is stirred for about 4 hours at 100 ° C. To make the reaction mixture, it is concentrated by evaporation, the residue is stirred with a small amount of ice water and extracted with methylene chloride. The combined organic phases are dried over sodium sulphate and concentrated by evaporation. The unpurified, yellowish-brown product is purified by chromatography on an aluminum oxide column ( III) with methylene chloride / methanol (98.5: 1.5) i Yield: 250 mg (36% of theory) Rf value: 0.70 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia solution = 9: 1: 0.01) Mass spectrum (ESI "): m / z = 275 [MH] The following compounds are obtained analogously to Example 4: 1) 4- [(3-bromophenyl) ammo] -6- (. {L- [(diethoxyphosphoryl) -methyl] -piperidin-4-yl] .}. amino) -pyrimido [5, 4-d] pyrimidine Rf value: 0.36 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia solution = 90: 10: 0.5) Mass spectrum (El): m / z = 549, 551 [ M] (2) 4 - [(3-bromophenyl) amino] -6- [(1 -. {[[(Ethoxy (methyl) -phosphoryl] -methyl} -piperid? n-4-yl) amino] -pyrimido [5, 4-d] pir imi di na (the reaction with diethyl oxe-1-phosphine in tetrahydrofuran) Rf value: 0.25 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia solution = 90: 10: 1) Mass spectrum (El): m / z = 519, 521 [M] + E j em lo 5 4- [(3-chloro-4-fluorophenyl) amino] -6- [4-amino-4- (methoxycarbonyl) -piperidin-1-yl] -pyrimido [5, 4-d] pyrimidine One suspension of 720 mg of 4- [(3-chloro-4-fluoro-phenyl) amino] -6-. { 4 - [(tert-butyloxycarbonyl) amino] - A - (methoxycarbonyl) -p i pe r i di n-1-i 1} The amount of [5, 4-d] p iim im ation in ip ml of methylene chloride is mixed with 2 ml of trifluoroacetic acid with stirring. The originated solution is allowed to stand overnight, with gas evolution, and then it is evaporated to dryness. The residue is extracted into methylene chloride, washed with dilute potassium carbonate solution and water, and dried over magnesium sulfate. The solvent is distilled off and stirred with a small amount of methane! the remaining yellow resin. Suction is filtered ^^^^ ^ ^ ^ g yellow precipitate, wash with a small amount of cold methanol, and dry in a desiccator. Yield: 565 mg (97% of theory) Melting point: 182-184 ° C Mass spectrum (ESI +): m / z = 432, 434 [M + H] + E j lo lo 6 4- [(3-chloro-4-fluorophenyl) amino] -6- [4- ( { N, N-bis [2- (methoxycarbonyl) ethyl] amino.} Methyl) -piperidine -1-yl] -pyrimido [5, 4-d] pyrimidine A 1.00 g of 4 - [(3-c 1 oro-4-fluoro-phenyl) amino] -6- (4-aminomethyl-piperidin-1-yl) -pyrimido [5, 4-d] pir imi di na in 25 ml of methanol are added 0.73 ml of methyl acrylate. The reaction mixture is refluxed for four hours, and then 0.35 ml of methyl acrylate are added again. After another five hours under reflux, the reaction is almost complete, and the mixture is concentrated by evaporation. The unpurified, yellow-orange product is purified by chromatography on a silica gel column with ethyl ether / ethyl acetate / methanol (1: 1: 0.1) as eluent. Yield: 1.02 g (71% of theory) Melting point: 113-118 ° C Mass spectrum (ESI +): m / z = 560, 562 [M + H] + The following compounds are obtained analogously to Example 6 (1) A - [(3-chloro-4-fluorophenyl) amino] -6- [3 - ( {N, N-bis [2- (methoxycarbonyl) ethyl] amino.} Methyl) -p? peridin-1-yl] -pyrimido [5, 4-d] pyrimidine Rf value: 0.90 (silica gel, melamine chloride and no / metanus 1 / s or 1 aqueous concentrated ammonia = 90:10 : 0.1) Mass spectrum (ESI +): m / z = 560, 562 [M + H] + (2) 4 - [(3-chloro-4-fluorophenyl) amino] -6- [3 ( { [2- (methoxycarbonyl) ethyl] amino.} Methyl) -piperidin-1-yl] -pyrimido [5, 4-d] pyridinone (1.5 equivalents of methyl acrylate are used alone ). Rf value: 0.60 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia solution = 90: 10: 0.1) Mass spectrum (ESI +): m / z = 474, 476 [M + H] + 3 4 - [(3-chloro-4-fluorophenyl) ami no] 6-. { 4-met? L-4- [2- (methoxycarbonyl) ethyl] amino-piperidinyl 1} -p i rimido [5, 4 -] p r imid (only 1.4 equivalents of methyl acrylate are used). Melting point: 134-135 ° C Mass spectrum (ESI +): m / z = 474, 476 [M + H] + -^^^^ * ^ gjg ¿g¡ ^^^^ tíífcS ^^^^^ (4) 4- [(3-bromophenyl) amino] -6- (. {L- [l, 2 bis ( methoxycarbonyl) -ethyl] -piperidin-4-yl.}. amino) pyrimido [5, 4-d] pyrimidnone (the reaction was carried out with dimethyl maleate in dioxon). Melting point: 193 ° C Mass spectrum (ESI "): m / z = 542, 544 [MH]" (5) 4- [(3-bromophenyl) amino] -6- [(1-. - [(ethoxycarbonyl) methyl] -2- (ethoxycarbonyl) -ethyl.} - p? peridin-4-yl) amino] -pyrimido [5, 4-d] pyrimidine (the reaction was carried out with distyl glutaconate in dioxane) Melting point: 132 ° C Mass spectrum (ESI +): m / z = 586, 588 [M + H] + (6) 4 - [(3-chloro-4-fluoro-phenyl) amin] 6 [(trans-4- { [2- (methoxycarbonyl) -ethyl] amino] cyclohex-1-yl) amino] -pyrimido- [5, 4-d] pyrimidine (The reaction was carried out with 1.3 equivalents of methyl acrylate) Melting point: 142-144 ° C Mass spectrum (El): m / z = 473, 475 [M] + (7) 4 - [(3-chloro-4-fluoro-phenol ) amin? > ] -6- [(trans-4- { [2- (benzyloxycarbonyl) -ethyl] amino] cyclohex-1-yl) amino] -pyrimido- [5, 4-d] pyrimidine The reaction was carried out with 1.3 equivalents of benzyl acrylate in acetonityrol) Melting point: 182-184 ° C Mass spectrum (ESI +): m / z = 550, 552 [M + H] + (8) 4 - [ (3-Chloro-4-fluoro-phenyl) amino] -6 ( { 1- [2- (methoxycarbonyl) -ethyl] piperidin-3-yl} amino-pyrimido [5, 4-d] pyre imi di na (The reaction was carried out with 1.1 equivalents of methyl acrylate) Melting point: 132 ° C Mass spectrum (ESI +): m / z = 460, 462 [M + H] + (9) 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- (. {1- [2- (tertbutyloxycarbonyl) -ethyl] -piperidin-3-yl-amino) -pyrimido [5 , 4-d] pyrimidine (The reaction was carried out with 1.03 equivalents of tert.-butyl acrylate | in acetonitrile) and Rf: 0.52 (silica gel, ethyl acetate / methanol = 9: 1) Mass spectrum (ESI + ): m / z = 502, 504 [M + H] + i (10) 4 - [(3-chloro-4-fluoro-phenyl) amino] -6- ( { 1- [2- (phenyloxycarbonyl) -ethyl] -piperidin-3-yl.} amino) -pyrimido [5, 4-d] pyrimidine The reaction was carried out with 1.04 equivalents of phenyl acrylate in acetonitrile Melting point 130 ° C Mass spectrum (ESI +): m / z = 522, 524 [M + H] (11) 4 - [(3-chloro 4-fluoro-phenol) aminq] -6- ( { 1- [2- (benzyloxycarbonyl) -ethyl] -piperidin-3-yl} amino) -pyrimido [5, 4-d] pyrimidine ( The reaction was carried out with 1.0 equivalents of benzyl acrylate Melting point 104 ° C Mass spectrum (ESI +): m / z = 536, 538 [M + H] + (12) 4 - [(3-chloro- 4-fluoro-phenyl) amino] -6- [(trans-4. {[[2- (phenyloxycarbonyl) -ethyl] -amino}. Cyclohex-1-yl) amino] -pyrimido [5, 4-d ] pyrimidine (The reaction was carried out with 1.0 equivalents of phenyl acrylate in acetonitoplo Rf: 0.20 (silica gel chloride of me ti 1 e no / me ta no 1 = 9: 1) Mass spectrum (ESI +): m / z = 536, 538 [M + H] (13) 4 - [( 3-chloro-4-fluoro-phenyl) aminp -6- [(trans-4- { [2- (indane-5-yloxycarbonyl) -ethyl] amino.}. Cyclohex-l-yl) amino] -pyrimido [5,4-d] pyrimidine (The reaction was carried out with 1.09 equivalents of indan-5-yl acrylate in acetonitrile). Indan-5-yl acrylate is obtained by the reaction of indan-5-ol with acryloyl chloride in the presence of triethylamine) Rf: 0.23 (silica gel, methylene chloride 1 ene / me ta no 1 = 9: 1 ) Mass spectrum (ESI +): m / z = 576, 578 [M + H] + (14) 4 - [(3-chloro-4-fluoro-phenyl) amin ©] -6- (. {1- [2- (indan-5-yl-oxycarbonyl) -ethyl] -piperidin-3-yl} amino) -pyrimido [5,4-d] pyrimidine (The reaction was carried out with I 1 .O 8 equivalents of indan-5-yl acrylate in acetonitrile) Rf: 0.50 (silica gel methylene chloride / methanol = 9: 1) Mass spectrum (ESI "): m / z = 560, 562 [MH]" (15) 4 - [(3-Chloro-4-fluoro-phenyl) amino] -6 - (. {- 1- [2- (diethoxy-phosphoryl) -ethyl] -piperidin-3-yl.}. Ami not) -pyr imi do [5, 4-d] pir imi di na (The reaction was carried out with 1.04 equivalents of diethyl ester of vinylphosphonic acid in acetonitrile) Rf: 0.46 (silica gel, ethyl acetate 1 / methylbenzoate / ammonium) iaco aqueous concentrate 90: 10: 2) Espect Ro of mass (ESI +): m / z = 538, 540 [M + H] + Example 7 4 - [(3-chloro-4-fluorophenyl) amino] -6-. { [trans-4 oxo-morfol i n-4-yl) -cyclohex-1-y1] amino} pyrimido [5, 4-d] pyrimidine A 970 mg of [(3-chloro-4-fluorophenyl) amino] -6- ( { trans-4- [(2-hydroxyethyl) ami no] -cyclohex-1-yl .) amino) -pyrimido- [5, 4-d] pyrazine in 5 ml of dimethylformamide at room temperature add 0.61 ml of di isop r op i 1 -eti 1 amine and 0.39 ml of bromoacetat or ethyl . The suspension is heated briefly to 50 ° C in a water bath until a clear solution is formed. The reaction mixture is then stirred for a further three hours in an atmosphere. To treat the mixture, it is combined with water and ice. The phases are separated and the aqueous phase is extracted with ethyl acetate. The combined organic phases are washed with water and with saturated sodium chloride solution, dried over magnesium sulfate and concentrated by evaporation. The crude product is purified by chromatography on a silica gel column with methylene chloride / methanol (98.5: 1.5 to 97: 3) as eluent. The product is obtained exclusively as a yellow crystalline solid. Yield: 466 mg (44% of theory) Melting point: 213-223 ° C Mass spectrum (ESI +): m / z = 472, 474 [M + H] + The following compound is obtained analogously to Example 7: (1) 4 - [(3-chloro-4-fluorophenyl) amino] -6-. { 4 [(2-oxo-morpholin-4-yl) methyl] -piperidin-1-yl} -pyrimido [5, 4-d] pir imi di na (the reaction was carried out in acetonitrile as solvent, predominantly producing the non-cyclized product which was cyclized to form the lactone by heating with a small amount of p-acid). toluene sulfonic acid in toluene) Melting point: 202-204 ° C Mass spectrum (ESI +): m / z = 472, 474 [M + H] + E j emp lo 8 4 - [(3-cyoro-4-fluorophenyl) amino] -6- [(trans-4 { [.2- N - [(ethoxycarbon ni 1) useful] - N - metilami no.}. - __. ethyl) sulfonyl] amino} -cyclohex-l-yl) amino pyrimido [5, 4-d] pyrimidine A 195 mg of [(3-chloro-4-fluorophenyl) arrimo] -6- ( { trans-4- [(vinylsulfonyl) amino] - cyclohex-1-yl.). amino pyrimidi - [5, 4-d] pir imi di na in 10 ml of methanol at room temperature add 0.21 ml of diis op r op i 1 -eti 1 amine and 176 mg of sarcosine methyl ester hydrochloride The reaction mixture is refluxed for approximately 25 hours After the reaction is complete, the mixture is concentrated by evaporation, since the product is partly in the form of a free acid, it is dissolved The residue is again taken up in methanol, cooled, under a nitrogen atmosphere, in an acetone-free or dry-ice bath, and combined with 0.2 ml of thionyl chloride, after heating to room temperature the solvent is distilled in va When the residue is dissolved in methylene chloride / methylanol, it is washed with dilute sodium carbonate solution, dried over magnesium sulfate. It is concentrated by evaporation.] The unpurified product, brownish in color, is purified by chromatography on a column of ¡Ü &^ ßanuáaM silica gel with methylene chloride / methanol (98: 2). Yield: 51 mg (22% of theory) Melting point: 171-174 ° C Mass spectrum (ESI +): m / z = 581, 583 [M + H] + The following compounds are obtained analogously to Example 8 : (1) 4- [(3-chloro-4-fluorophen? L) amino] -6-. { [trans-4- ( { [2- (2-Oxo-morpholin-4-yl) -ethyl] sulfo-nyl} amino) -cyclohex-1-yl] amino) -p-rimido [5 , 4-d] -pyrimidine (by reaction with hydrochloride of (2-hydroxy-1-ethyl-1-amino) - to ethyl acetate in ethanol, subsequent re-esterification as developed in E j emp 1 or 8) Rf value: 0.39 (silica gel, me 111 ene / me tano chloride 1 = 95: 5) Mass spectrum (El): m / z = 578, 580 [M] + (2) 4- [ (3-chloro-4-fluorophenyl) amine] -6-. { [trans-4-. { [(2- (2 - { [(Methoxycarbonyl) methyl] amino ethyl) sulfonyl] amino.}. -cyclohex-1-yl] amino] -pyrimido [5, -d] pyrimidine Melting point: 178- 182 ° C Mass spectrum (ESI +): m / z = 567, 569 [M + H] + The following compounds can also be obtained analogously to the preceding examples and other methods known from the literature: (1) 4- [ (3-methylphenyl) amino] -6- [(methoxycarbonyl) -methyl] -piperidin-4-yl} amino) -pyrimido [5, -d] pyrimidine 2) 4- [(3-chlorophenyl) amino] - 6- ( { L- [(methoxycarbonyl) -methyl] -piperidin-4-yl.}. Amino) -pyrimido [5, 4-d] pyrimidine 3) 4 - [(3-ethynylphenyl) amino] -6 - ( { 1- [(Methoxycarbonyl) -methyl] -piperidin-4-yl.}. Amino) -pyrimido [5, 4-d] pyrimidine (4) 4- [(3-trif luoromethylphenyl) amino] -6- ( { 1 - [(methoxycarbonyl) ethyl] -piperidin-4-yl.}. amino pyrimido [5, 4-d] pyrimidine (5) 4- [(3-bromofenyl) amino] -6- ( { 1 [(methoxycarbonyl) -methyl] -piperidin-4-yl} amino pyrimido [5, -d] pyrimidine (6) 4- [(4-amino-3,5-dibromo-f-enyl) amino] -6 - (. {1- [(methoxycarbonyl) methyl] -piperidin-4] -yl.}. amino pi imi do [5, 4-d] pir imi di na (7) 4 - [(4-amino-3,5-dichloro-phenyl) aminF] -6 (. {1- 1- [ (methoxycarbonyl) methyl] -piperidin-4-ylamino) -pyrimido [5, 4 - d] pyrazole ^^^ á ^^^^^^^^^^^^^^^^^^^ ti ^^^^^^^^^^^^ (8) 4 - [(indol-5-yl) ammo] -6- ( { L- [(methoxycarbonyl) -methyl] -piperidin-4-yl} amine) -pyrimido - [5, 4 -d] pyrimidine (9) 4 - [(3-bromophenyl) amino] -6- (N- { 1 - [(methoxycarbonyl) methyl] -piperidin-4-yl.} - N -methylamino) - pyrimid [5, 4-d] pyrimidi (10) 4 - [(3-bromophenyl) amino] -6- (. {l- [(methoxycarbonyl) -ethyl] -piperidin-4-yl} amino) -pyrimido- [5, 4-d] pir imi di na (11) 4- [(3-chlorofenyl) amino] -6- (. {1- [(ijieto-xicarbonyl) -ethyl] -piperidin-4-yl.}. amino) -pyrimidp- [5, -d] pyrimidine (12) 4 - [(3-chloro-4-fluoro-phenyl) amin] -6 (. {1- [( methoxycarbonyl) ethyl] -piperidin-4-yl.}. amino pyrimid [5, 4-d] pyrimidine (13) 4 - [(3-methylphenyl) amino] -6- ( { [(methoxy carbonyl) -ethyl] -piperidin-4-yl.}. amino) -pyrimido [5, 4 -d] pyrimidine (14) 4 - [(3-ethynylphenyl) amino] -6- (. {l - [(methoxycarbonyl) ethyl] -piperidin-4-yl} amino) -pyrimido [5, 4 -d] pyrimidine (15) 4- [(3-chlorophenyl) amino] -6- ( { l- [ 1,2 bis (methoxycarbonyl) -ethyl] -piperidin-4-yl} amino) pyrimido [5, 4-d] pyrimidine (16) 4 - [(3-chlorophenyl) amino] -6- [(1- (1-l- [(methoxycarbonyl) methyl] -2- (methoxycarbonyl) -ethyl); -piperidin-4-yl) amino] -pyrimido [5, 4-d] pyrimidine (17) 4 - [(3-chlorophenyl) amino] -6- [(1- {1- [(etho-xicarbonyl)] methyl] -2- (ethoxycarbonyl) -ethyl.}. -pipen din-4-yl) amino] -pyrimido [5, 4-d] pyrimidine (18) 4- [(3-chlorophenyl) amino] -6 - ( { l- [l, 2-bis (ethoxycarbonyl) -ethyl] -piperidin-4-yl.}. amino) -pyrimido [5, 4-d] pyrimidine (19) 4 - [(3 chloro-enyl) amino] -6- ( { 1- [(diethoxyphosphoryl) methyl] -piperidin-4-yl} amino) -pyrimido- [5, 4-d] pyrazine (20 ) A - [(3-chlorophenyl) amino] -6- (. {1- (dimethyl o-xiphosphoryl) -methyl] -piperidin-4-yl} amino) -pyrimido- [5, 4-d] -pyr imi di na (21) 4 - [(3-chlorophenyl) amino] -6- [(1- {[[(tieto-xi) (methyl) -phosphoryl] methyl} - piperidin-4-yl ) Not me! pyrimido [5, 4-d] pyrimidine (22) 4- [(3-chlorophenyl) amino] -6- [(1- {[[(eto-xi) (me ti 1) - phosph or i] ti 1.}. -pipe ri din-4-i 1) amino-pyrimido [5, -d] pyrimidine (23) 4 - [(3-chlorophenyl) amino] -6- (. {l- [(Jiexi loxycarbonyl) methyl] -piperidin-4-yl.}. amino) -pyrimido [5, 4-d] pyrimidine , ._: _i4 ¿. "_.... c [(methoxy pyrimido [(methoxy pyrimido [(methoxycarbonyl) methyl] -N-methylamino] butylamino) -pyrimido [5, -d] -pyrimidine (27) 4- [(3-chlorofenyl) amino] -6- (3- { N, N-bis [(methoxycarbonyl) -methyl] amino.}. Propylamino) -pyrido [5,4-d] pyrimidine (28) 4 - [(3-chlorophenyl) amino] -6- (. { l- [(methoxycarbonyl) -methyl] -piperidin-3-yl} amino) -pyrimido- [5, 4 -d] pi rimidine (29) 4 - [(3-bromophenyl) amino] - 6- ( { L- [(methoxycarbonyl) -methyl] -piperidin-3-yl.}. Amino) -pyrimigo- [5, 4-d] pyrimidine (30) 4 - [(3-methylphenyl) amino] ] -6- ( { L- [(grandson xicarbonyl) -methyl] -piperidin-3-yl.}. Amino) -pyrimido- [5, 4-d] pyrimidine (31) 4 - [(3-ethynylphenyl ) amino] -6- ( { l- [(methoxycarbonyl) methyl] -piperidin-3-yl.}. amino) -pyrimid © [5, 4-d] pyrimidine j ^ j ^^^ Aí ^^^^ 4 (37) 4- [(3-chlorophenyl) amino] -6- (4- { N [(methoxycarbonyl) methyl] -N-methylamino.}. -piperidine -1 il) -pyrimido [5, -d] -pyrimidine (38) 4- [(3-chlorophenyl) amino] -6- (4- [(methoxy carbonyl) -methyl] -amino-piperidin-1-yl) -pyrimido [5, 4-d] pyrimidine (39) 4 - [(3-chlorophenyl) amino] -6- (4- { N, N-bis [(methoxycarbonyl) -methyl] amino) -piperidin-1 -yl) -pyrimido [5, -d] -pyrimidine (40) 4- [(3-chlorophenyl) amino] -6- (4. {Nr (dimethoxyphosphoryl) methyl] -N-methylamino}. -piperidin-1-yl) -pyrimido [5, -d] -pyrimidine (41) 4- [(3-chlorophenyl) amino] -6- [4- (N- { [(ethoxy) - (methyl) phosphoryl ] met? l.). N -methylamino) -p? peridin-1-yl] -pyrimido- [5, 4-d] pyrimidine (42) 4- [(3-chlorophenyl) amino] -6- [4 - ( { N- [(methoxycarbonyl) methyl] -N-methylamino.} Methyl) -piperidin-1-yl] -pyrimido- [5,4-d] pyrimidine (43) 4- [(3-bromof enyl) amino] -6- [4 - ( {N- [(methoxycarbonyl) methyl] -N-methylamino] methyl) -piperidin-1-yl] -pyrimido- [5, 4-d] pyrimidine (44) 4- [(3-methylphenyl) amino] -6- [4- (. { N- [(methoxycarbonyl) methyl] -N-methylamino} met l) -p? peridin-1-? l] -pyrimido- [5, 4-d] pyrimidine (45) 4- [(3-ethynylphenyl) amino] -6- [4- ( {N [( methoxycarbonyl) methyl] -N-methylamino.} me ti 1) - piper? din-1-? l] -pyrimido- [5, 4-d] pyrimidine (46) 4- [(3-chlorophenyl) amino] - 6- [4 ( {N [(ethoxycarbonyl) methyl] -N-methylamino.} Met? L) -piperidin-1-yl] -pyrimido- [5,4-d] p? Rimi-dine (47) 4 - [(3-chlorophenyl) amino] -6- [4- (. {[[(Xicarbonyl) -methyl] -amino] methyl) -piperidin-1-yl] j 48) 4- [(3-chlorophenyl) amino] -6- [4- ( {N, N-bis [(ethoxycarbonyl) -methyl] amino] methyl) -piperidin-1-yl] -pyrimido [ 5, 4-d] -pyrimidine (49) 4- [(3-chlorophenyl) amino] -6- [4- (. {N- [(dimethoxy-phosphoryl) methyl] -N-methylamino] methyl) -piperidin-1-yl] -pyrimido- [5, 4-d] irimidine 50) 4- [(3-chlorophenyl) amino] -6- [4- ( { N [(diethoxy-phosphoryl) methyl] - N-methylamino.} Methyl) -piperidin-1-yl] -pyrimido- [5, 4-d] pyrimidine (51) 4- [(3-chlorofenyl) amino [-6- [4- (N . { [(ethoxy) - (me ti 1) phosphoryl] methyl} -N-methylamino) methyl] -piperidin-1-yl] -pyrimido- [5, 4 ~ d] pyrimidine (52) 4- [(3-chlorophenyl) amino] -6- (2- {1 [(methoxycarbonyl ) methyl] -piperidin-4-yl.}. ethylamin F-pyrimido [5, 4-d] -pyrimidine (53) 4- [(3-bromophenyl) amino] -6- (2. {1 l [(methoxycarbonyl) methyl] -piperidin-4-yl.} ethylamino) -pyrimido [5, -d] -pyrimidine (54) 4 - [(3-methylphenyl) amino] -6 (-. {1 [(methoxycarbonyl) methyl] -piperidin-4-yl} ethylamino F) -pyrimido [5, -d] -pyrimidine (55) 4- [(3-ethynylphenyl) amino] -6- (2- { [(methoxycarbonyl) methyl] -piperidin-4-yl} ethylamin) -pyrimid [5, 4-d] -pi rimide (56) 4- [(3-chlorophenyl) amino] -6- ([(methoxycarbonyl) methyl] -piperazin-1-yl .}. ethylamin pir imi do [5, 4-d] -pyrimidione (57) 4- [(3-bromophenyl) amino] -6- (- { 4 [(methoxycarbonyl) methyl] - piperazm-1-yl.] et.lamin) -pyrimido [5, 4-d] -pyrimidine (58) 4- [(3-ethynylphenyl) amino] -6- (-. {4 ([(methoxycarbonyl) methyl] ] -piperazin-1-yl) ethylamino) -pyrimido [5, 4-d] -pyrimidine (59) 4- [(3-methylphenyl) amino] -6- (-. {4 [(methoxycarbonyl) methyl] -piperazin-1-yl} ethylamine pyrimido [5, 4-d] -pyrimidine (60) 4- [(3-chlorophenyl) amino] -6- [(dimethoxy-phosphoryl) methyl] -piperazin-1-yl} ethylamino) -pyrimido [5, 4-d] -pipmidine (61) 4- [(3-chlorophenyl) amino] -6- (2- {1 [(dimethoxy-phosphoryl) ethyl] -piperidin-4-yl} .}. ethylamino) -pyrimido [5, 4-d] -pyrimidine (62) 4- [(3-chlorophenyl) amino] -6- [2- (4. {[[(Ethoxy) - (methyl) phosphoryl] methyl.}. -piperazin-1 -yl) ethylamino] -pyrimido [5, 4-d] -pyrimidine (63) 4- [(3-chlorophenyl) amino] -6- [? . { [(ethoxy) - (methyl) phosphoryl] methyl} -piperidin-4-yl) ethylamino] -pyrimido [5, 4-d] -pyrimidine (64) 4- [(3-chlorophenyl) amino] -6- (3. {l [(methoxycarbonyl) methyl] - piperidin-4-yl-Jpropylamino) -pyrimido [5, 4-d] -pyrimidine (65) 4- [(3-chlorophenyl) amino] -6-C_-. { 4- [(methoxycarbonyl) methyl] -piperazin-1-yl-Jpropylamino) -pyrimido [5, 4-d] -pyrimidine (66) 4- [(3-bromophenyl) amino] -6- (3-. {4 [(methoxycarbonyl) ethyl] -piperazin-1-yl-Jpropylamino) -pyrimido [5, 4-d] -pyrimidine (67) 4- [(3-methylphenyl) amino] -6- (3-. {4- [(methoxycarbonyl) methyl] -piperazin-1-yl-Jpropylamino) -pyrimido [5, 4-d] -pyrimidine (68) 4- [(3-ethynylphenyl) amino] -6- (3 [(methoxycarbonyl) methyl] - piperazin-1-yl-propylamino) -pyrimido [5, 4-d] -pyrimidine (69) 4- [(3-chloro-4-fluoro-phenyl) aminq] -6- (3 -. {4 - [(methoxycarbonyl ) methyl] -piperazin-l-yl-propylamino) -pyrimido- [5, 4-d] pyrimidine (70) 4 - [(3-chlorophenyl) amino] -6- (. {l- [(ethoxy carbonyl) -methyl] -piperidin-4-yl Jmethylamino) -pyrimido [5, 4-d] pyrimidine (71) 4 - [(3-bromophenyl) amino] -6 - ((l- [(ethoxy carbonyl) -methyl] - piperidin-4-yl.}. methylamino) -pyrimido [5, 4-d] pyrimidine (72) 4- [(3-methylphenyl) amino] -6- (. {1 l [(ethoxycarbonyl) -methyl] - piperidin-4-ylmethylamino pyrimido [5, 4-d] pir imidine (73) 4- [(3-ethynylphenyl) amino] -6-r (. { l- [(Ethoxycarbonyl) -methyl] -piperidin-4-yl} methylamino pyrimido [5, 4-d] pyrimidine (74) 4- [(3-chlorophenyl) amino] -6-. { [4- ( { N- [(ethoxycarbonyl) methyl] -N-methylamino] methyl) -ciclfhex-1-yl] methylamino} -pyrimido [5, 4-d] pyrimidine (75) 4- [(3-chlorofenyl) amino] -6- [(4- {N- [(ethoxycarbonyl) methyl] -N-methylamino] -cyclohex-1 il) ethylamino] -pyrimido [5, 4-d] pyrimidine (76) 4- [(3-chlorophenyl) amino] -6- [(4 0) 4- [(3-ethynylphenyl) amino] -6 - [(4 [(ethoxycarbonyl) methyl] -amino]. -cyclohex-1-yl) amino] -pyrimido [5, 4-d] -pyrimidine 1 ) 4- [(3-chlorophenyl) amino] -6-. { [4- ( { N- [(ethoxycarbonyl) methyl] -N-methylamino] methyl) cyclichex-1-yl] amino} -pyrimido- [5, 4-d] pyrimidine (82) 4- [(3-chlorophenyl) amino] -6- (. {4- [3- ({N-ethoxycarbonyl) methyl] -N-methylamino] .}. propyl) aminc car-bonyl] -cyclohex-l-yl-amino} pyrimidine [5, 4 d] pyrimidine 83) 4- [(3-chlorophenyl) amino] -6-. { [4- ( { L- [(methoxycarbonyl) methyl] -piperidin-4-yl.}. Aminocarbonyl) -cyclohex-1-yl] -aminoj-pyrimido [5, 4-d] pyrim :. dyne 84) 4- [(3-chlorophenyl) amino] -6-. { [4- ( { 4 [(methoxycarbonyl) methyl] -piperazin-1-yl}. Carbonyl) cyclohex-1-yl] amino} -pyrimido [5, -d] pyrimidine (85) 4- [(3-chlorophenyl) amino] -6- [4- (2- { N [(ethoxycarbonyl) methyl] -N-methylamino} ethyl) -piperazin-1-yl] -pyrimido- [5, 4-d] pyrimidine (86) 4 - [(3-chlorofenyl) amino] -6- (4 -. {1- (methoxycarbonyl) methyl] -piperidine -4-yl.}. -piperidin-1-yl) -pyrimido [5, 4-d] pyrimidine (87) 4 - [(3-chlorophenyl) amino] -6-. { 7- [(methoxycarbonyl) -methyl] -2,7-diaza-spiro [4.4] non-2-yl} -p i rimido [5, 4 - d] p i r imi di II¡ii? __ & _ ^ ______________ or __ ^^ (88) 4- [(3-chlorophenyl) amino] -6- [C -. { 1 [(methoxycarbonyl) methyl] -piperidin-4-yl} -piperidin 4-yl) amino] -pyrimido- [5, 4-d] pyrimidine (89) 4- [(3-chlorophenyl) amino] -6- (. {1 l [(methoxycarbonyl) -methyl] -piperidine- 4-yl.}. Amino) -pyrido [3,4-d] pyrimidine (90) 4 - [(3-bromophenyl) amino] -6- (. {1 l- [(methoxycarbonyl) -methyl] -piperidine- 4-yl.}. Amino) -pyrido [3,4-d] pyrimidine (91) 4 - [(3-methylphenyl) amino] -β- (. {1 l- [(methoxycarbonyl) -methyl] -piperidine- 4-yl.}. Amino) -pyrido- [3,4-d] pyrimidine (92) 4 - [(3-et inyl-enyl) amino] -6. { 1- [(methoxycarbonyl) ethyl] -piperidin-4-yl} amino) -pyrido [3,4-d] pyrimidine (93) 4 - [(3-chloro-4-fluoro-phenyl) aminF] -6 ( { 1- [(methoxycarbonyl) methyl] -piperidin-4-) il.}. amino pyrido [3,4-d] -pyrimidine (94) 4 - [(3-chlorophenyl) amino] -6- (. {l- [(? -tetoxycarbonyl) -methyl] -piperidin-4 -yl.}. amino) -pyrido [3,2-d] pyrimidine (95) 4 - [(3-bromofenyl) amino] -6- (X- [(methoxycarbonyl) -methyl] -piperidin-4-) il.}. amino) -pyrido [3,2-d] pyrimidine ____u (96) 4- [(3-methylphenyl) amino] -6- (. {l- [(methoxycarbonyl) -methyl] -piperidin-4-yl} amino) -pyrido [3, 2-d] pyrimidine (97) 4 - [(3-ethynylphenyl) amino] -6- (. {l- [(methoxycarbonyl) methyl] -piperidin-4-yl} amino) -pyrido [, 2 d] pyrimidine ( 98) 4 - [(3-chlorophenyl) amino] -7- ( { 1 - [(methoxycarbonyl) -methyl] -piperidin-4-yl} amino) -pyrido [4, 3-d] pyrimidine ( 99) 4 - [(3-chloro-enyl) amino] -7 - ( { 1- [(methoxycarbonyl) -methyl] -piperidin-4-yl] -amino) -pyrimido [4,5-d] pyrimidine (100) 4 - [(3-chlorophenyl) amino] -7- (. {1 l- [(grand-xicarbonyl) -methyl] -piperidin-4-yl} amino) -pyrido- [2, 3 - d] pir imi di na (101) 4- [(3-chlorophenyl) amino] -6- [4-amino-4 (methoxycarbonyl) -piperidin-1-l] -pyrimido [5, 4-d] pyrimidine (102) 4- [(3-bromophenyl) amino] -6- [4-amino-4 (methoxycarbonyl) -piperidin-1-yl] -pyrimido [5, 4 -d] pyrimidine (103) 4- [(3 -methylphenyl) amino] -6- [4-amino-4 (methoxycarbonyl) -piperidin-1-yl] -pyrimido [5, 4 -d] pyrim d i n a _i ________ Bi _? __ a _? ______ i (104) 4 - [(3-ethynylphenol) amino] -6- [4-aryne-4- (methoxycarbonyl) -piperidin-1-yl] -pyrimido [5, A -d ] pyrimidine (105) 4- [(3-chloro-4-fluoro-phenyl) amino] -6 [4-amino-4- (methoxycarbonyl) -p] peridin-1-yl] -pipramido [5, 4-d] ] pyrimidine (106) 4- [(1-Phenylethyl) amino] -6- (. {l- [(methoxycarbonyl) -methyl] -piperidin-4-yl} -amino) -pyrimido [5, 4- d] pyrimidine (107) 4 - [(3-chlorophenyl) amino] -6-. { [4 - (2-oxo-morpholin-4-yl) -cyclohex-1-yl] amino) -pyrimido [5, 4 -d] pyrimidine (108) 4- [(3-chlorophenyl) amino] -6- . { 4 - [(2-oxo-morpholin-4-yl) -methyl] -piperidin-1-yl} - pyrimidine [5, 4 d] pyrimidine (109) 4 - [(3-chlorophenyl) amino] -6-. { [2- (2? Oxo morph olin-4-yl) -ethyl] amino} -pyrimido [5, 4 -d] pyrimidine E j en lo 9 Coated tablets containing 75 mg of active substance 1 tablet core containing: Active substance 75.0 mg Calcium phosphate 93.0 mg _____ ^^^^^^ &? ^^^^^^^ Me ^^ aa ^^^^^^^^^^ M k ^ ^^^^ Cornstarch 35.5 mg Po 11 lp saw or IRRO 1 i donates 10.0 mg H i dr ox i p r opi lme ti 1 ce 1 u 1 osa 15.0 mg Magnesium stearate 1.5 mg 230.0 mg Preparation: The active substance is mixed with calcium phosphate, corn starch, polyvinylpyrrolidone, hydrox ipr op i lme ti 1 ce 1 u 1 osa, and half of the specified amount of magnesium stearate. In a tableting machine tablets of 13 mm diameter are produced, they are crushed through a sieve with a mesh size of 1.5 mm using a suitable machine-and mixed with the remaining amount of estearatp magnesium. This granulate is compressed in a tabletting machine to form tablets with the desired shape. Core weight: 230 mg Punch: 9 mm, convex The tablet cores thus prepared are coated with a film consisting essentially of hydroxypropylmethylcellulose. The finished coated tablets are polished with beeswax.

Weight of the coated tablet: 245 mg T h e 10 Tablets containing 100 mg of active substance Comp i s i c t ion: 1 tablet contains: Active substance 100.0 mg Lactose 80.0 mg Corn starch 34.0 mg Polyvinyl pyrrolidone 4.0 mg Magnesium stearate 2.0 mg 220.0 mg Method of preparation: The active substance, the lactose and the starch are mixed together and uniformly moistened with an aqueous solution of the product. After the moist composition has been tami Zada (mesh size 2.0 mm) and dried at 50 ° C in a drying tray type, it is again sieved (mesh size 1.5 mm) and the lubricant is added The finished mixture is compressed to form tablets. Weight of the tablet: 220 mg Diameter: 10 mm, biplanar, with facets on both sides and partial notch on one side.

E j p lo 11 Tablets containing 150 mg of active substance C ompo sition: 1 tablet contains: Active substance 50.0 mg Lactose powder 89.0 mg Corn starch 40.0 mg colloidal silica 10.0 mg Polyvinylpyrrolidone 10.0 mg Magnesium stearate 1.0 mg 300.0 mg Preparation: The active substance mixed with the lactose, corn starch and silica, is wetted with a 20% aqueous solution of polyvinylpyrrolidone, and is passed through a sieve with a mesh size of 1.5 mm. The granulate, dried at 45 ° C, was made again through the same sieve again, and metered with the specified amount of magnesium stearate. The tablets are compressed through the mixture. Tablet weight: 300 mg Punch: 10 mm, flat , ...._ *. »,«. . ,. "- ** ._. - - "- * * * - - ^^ ^^ _ ^ ^^^^ j E emp as 12 Hard gelatin capsules containing 150 mg of active substance 1 capsule contains: active substance 50.0 mg Cornstarch ( dry) approx 80.0 mg Lactose in (powder) approx 87.0 mg Magnesium stearate 3.0 mg approx 420.0 mg Preparation: the active substance with the excipients are mixed, passed through a sieve with mesh size of 0.75 mm and homogeneously mixed using a apropiad apparatus The final mixture is packed into hard gelatin capsule size 1. Capsule filling: approx. 320 mg Capsule shell: hard gelatin capsule size 1.

Th e 13 Suppositories containing 150 mg of active substance 1 suppository contains Active substance 150.0 mg Polyethylene glycol 1500 550.0 mg Po 11 eti 1 e ngl ico 1 6000 460.0 mg Polyoxyethylene sorbitan monostearate 40.0 mg 2,000.0 mg Preparation: After melting the table for suppositories The active substance is distributed homogeneously within it, and the melt is poured into previously cooled molds.

E xployment 14 Suspension containing 50 mg of active substance 100 ml of suspension contains: Active substance 1.00 Na salt of carboxymethylcellulose 0.10 g methyl p-Hydroxybenzoate 0.05 gp - Propylene carbonate H 0.01 g Glucose 10.00 g Glycerol 5.00 g Sorbitol solution 70% 20.00 q Flavor 0.30 g Distilled water up to 100 ml Preparation: Distilled water is heated to 70 ° C. Dissolve in it with agitation, the P 'h i dr ox ib en z o a t o s of methyl and propyl together with the glycerol and sodium salt of carboxymethyl cellulose. The solution is cooled to room temperature and the active substance is added, with stirring, and dispersed homogeneously. After adding and dissolving the sugar, the sorbitol solution and the flavoring, the suspension is evacuated with agitation, to remove the air. 5 ml of suspension containing 50 mg of active substance.

E x p ply 15 Ampoules with 10 mg of active substance C ompo s i c ons: Active substance 10.0 mg Hydrochloric acid 0.01 N, sufficient amount Double-distilled water up to 2.0 ml Preparation: The active substance is dissolved in the required amount of O.OIN HCl, isotried with common salt, sterile filtered and transferred into 2 ml ampoules.

E n g it s 16 Ampoules containing 50 mg of active substance C omp o s ss: Active substance 50.0 mg Hydrochloric acid O.OIN, sufficient amount Double-distilled water up to 10.0 ml Preparation: The active substance is dissolved in the required amount of O.OIN HCl, made isotonic with common salt, sterile filtered and transferred into 10 ml ampoules.

E n g lish 17 Capsules for inhalation of powders containing 5 mg of active substance 1 capsule contains: Active substance 5.0 mg Lactose for inhalation 15.0 mg 20.0 mg hydrochloric acid ÍN the pH value of the solution is adjusted. The resulting solution is filtered and transferred into appropriate containers for manual nebulizers (cartridges). Container content: 4.5 g _-__ .. > ._- .. and.,. Jéy, .yír * .r. Y% _.

Claims (3)

RE IVIND I C,, A "£ C", I ONE S Bicyclic heterocycles of the formula r e R_ R. \ / wherein Ra means a hydrogen atom or an alkyl group of C? -, Rb means a phenyl, benzyl or 1-phenylethyl group in which the phenyl nucleus is substituted in each case by the groups Ri to R3, while Ri and R2, which may be the same or different, each meaning a hydrogen atom, fluorine, chlorine, bromine or iodine, an alkyl group of C? _, hydroxy, aleo): i of C? - , C3-C cycloalkyl, C4-6 cycloalkoxy, C2-5 alkenyl or C2-5 alkynyl, an aryl, aploxy, arylmethyl or arylmethoxy group, a C3-5 alkenyloxy group or C3- 5, while the more saturated portion may not be linked to the oxygen atom, ^^ g | ¿-CH = NC (-AB) = N-, where the left end of these bridges is linked to position 5 and the right end of these bridges is linked to position 6 of the pyrimidine ring, A means an -O-alkylene group of Ci 0 -cyclo 1 or - a 1 qu i 1 e of C4-7, -O-alkylene of C3-cycloalkylene of C3_7, -0-cy 1 or 1 qu 1 and not of C4-7 alkylene of C1-3 or -O-alkylene of C3-3-cycloalkylene of C3-7 - a 1 qu i 1 e not of C? _3, while the oxygen atom of the group before mentioned in each case is linked to the bicyclic aromatic ring, a - NR - a 1 qu i 1 ene of C? _8, rNR4"cycloalkylene of C3-7, - NR4 - a 1 qu i 1 ene of C1-3 cycloalkylene of C3_7, -NR4-cic 1 or to 1 qui 1 in o of 03.7-alkylene of C? _3 or -N R4 - to 1 qu i 1 ene of C? _3-cycloalkylene of C3 -7 - a 1 qu 1 ene of C1-3, while the portion -NR4- of the aforementioned groups in each case -is linked to the bicyclic heteroaromatic ring, and R 4 means a hydrogen atom cp an alkyl group of C 4 _4, an oxygen atom that is bonded to a carbon atom of group B, a group -NR-ci cl or a 1 qu i 1 ene of C4-7-NH -SO 2 -alkylene of C 4 -4 or -NR 4 -cyc 1 or 1 to 1 of C4-7 N (C alquilo _4 alkyl) -S 02- to 1 qu of C C _4, that the portion -NR4- of the aforementioned groups in each case is linked to the bicyclic heteroaromatic ring, and R4 is as defined above, a group -NR, where the latter is linked to a carbon atom of group B and R4 is as defined above, an azeti di ni 1 ene, pyrro 1 idini 1 ene, piperi di ni 1 enoohexahi dr oaz ep ini 1 ene group optionally substituted by one or two methyl groups, while in each case the cyclic nitrogen atom of the aforementioned groups is bonded to the bicyclic heteroaromatic ring, an azeti di ni 1 en - a 1 qu i 1 group C1-3 ene, pyrro 1 i di ni 1 en - a 1 qu i 1 ene of C1-3, piperidinylene-alkylene of C? _3 or he xahi dr oaz ep ini 1 en - a 1 qu i 1 ene de C1 -3, while in each case the cyclic nitrogen atom of the aforementioned groups is linked to the bicyclic heteroaromatic ring, a group 1, 4 -p ip erazini 1 e no or 1.4 h omop iperazini 1 e no, these groups each being linked to a carbon atom of group B, carbonyl is bonded to a nitrogen atom of group B, a group -NR4-cic 1 or a 1 qu 11 enca rb oni 1 ami no of C3-7, while the -NR4- portion is linked to the bicyclic omatic heteroa ring, and the nitrogen atom of the carbonylamino portion, which may be further substituted by an alkyl group of C? _4, is bonded to a carbon atom of group B, a group -NR4 - cic 1 or 1 qui 1 enea rb on i 1 ami no de C3-7-alkylene of C? -3, while the -NR4-portion is linked to the bicyclic heteroaromatic ring and the nitrogen atom of the carbonylamino portion can be further substituted by a C? -4 alkyl group, an azeti group di nor 1 in charge? i 1, pyrro 1 i di ni 1 encar bon i 1 o, p ipe ri di ni 1 in ca rb on i 1 oohexahidroazepini 1 en - ca rb on i 1 o, while in each case the cyclic nitrogen atom of the aforementioned groups are linked to the bicyclic heteroaromatic ring and the carbonyl group in each case is bonded to a nitrogen atom of group B, an azetidinylenecarbonyl group, pyrro 11 dini 1 enca rb on i 1 ami no, pi pe ri di ni 1 en # ^^^^ RgO-CO or a group RgO-CO- a 1 qu i 1 o of C? -2, while Rs means a hydrogen atom, an alkyl group of C? -4, which can? star substituted by a hydroxy group, C? -4 alkoxy, R60-CO, (R70-PO-OR8), (R7O-PO-R9), amino, C1-4 alkylamino or di- (C? ) - arrimo, or by an alkyleneimino group of 4 to 7 members, while in the aforementioned 6 to 7-membered alkyleneimino groups in each case a methylene group in the 4-position can be replaced by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, imino or N- (C? _4) alkyl group, a C3-7 cycloalkyl group or C3_7 cycloalkyl-C alquilo3 alkyl group, Rg, R7 and Re, which may be the same or different, in each case a hydrogen atom, an alkyl group of C? .8, which may be substituted by a hydroxy group, C? -4 alkoxy, amino, C? -4 alkylamino or di- (alkyl) C amino, or by an alkyleneimino group of 4 to 7 members, while the aforementioned 6 to 7 membered alkyleneimino groups in each case a methylene group in the 4 position can be replaced by an oxygen atom or sulfur, for "MYI a piperazmo or homop ip erazi group that is not substituted in position 4 by the group R? O, and additionally in a cyclic carbon atom by a group R60-CO, (R70 - PO - 0R8) -, (R70 -PO-R9), R60-CO alkyl of C? _4-, bis- (R60-CO) -alkyl of C? -4, (R70-P0-0R8) -alkyl of C? -4 or (R70-PO) -R9) -alkyl of C? -4, wherein Rg to R9 are as defined above and Rio means a hydrogen atom, an alkyl group of C? _, Formyl, C? -4 alkylcarbonyl or alkylsulfonyl of C? _, A piperazino or homop ip erazi group that is substituted in each case in position 4 by a group RgO - CO - a 1 qu i 1 o de C? -, bis - (RgO-CO) -alkyl of C? _4, (R70-PO-fR alkyl of C1-4 or (R7O-PO-R9) -alkyl of C1-4 where Rg to Rg are as a pyrrolidinyl, piperidinyl hexahi dr oaz ep ini 1 o group, substituted in the 1-position by the group R10, were defined in the foregoing, while the aforementioned 5 to 7-membered rings are each substituted di l i ona l in a carbon atom by a group R60-CO, (R70-PO-OR8), (R7O-PO-R9), R60-CO-alkyl of C 1 _4, bis- (R60-CO) -alkyl of C1 -4, (R7O-PO-OR9) -alkyl of C 1 _ 4 or (R70-PO-R9) -alkyl or of c wherein R (Rio are as defined above defined as is mentioned above, a pyrrolidinyl, piperidinyl hexahi dr or z epmi 1 o, substituted in the 1-position by a group R60-CO- to 1 qui 1 or of C bis- (RgO-XO) -alkyl of C? _4, ( R7O-PO-OR9) -C1-4 alkyl or R70-PO-R9) -C1-4 alkyl-, wherein Rg to Rg are as defined above, a 2-ox group or-1-mole, which may be substituted by one or two methyl groups, a 2-oxo-mo-1-mo-1-o-group, which is substituted at the 4-position by a hydrogen atom, by a C-alkyl group; ? _4, RgO-CO alkyl of C? _4, (R70-PO-OR8) -alkyl of C? -4, or (R70 PO- Rg) - a 1 qu i 1 o of C? _4, while Rg a Rg are as defined above and the aforementioned 2-oxo-morpholinyl groups are in each case linked to a carbon atom of group A, a cycloalkyl group of C5-7, which is substituted by an amino group, alkylamino of C 1-4 or di- (C 1-4 alkyl) -amino, and by a group R 50 CO, while R g is as defined as above, (R 7 O -PO - R g) - a 1 qu i 1 enimi of C? _4, where Rg to R < they are as defined in the foregoing, a group 1-pyrr or i di ni 1 or, 1-pi pe ri di ni 1 oo 1-azacic 1 ohep t-1-i 1 or where the two hydrogen atoms of a Methylene group are replaced by a linear chain C.sub.6 -alkylene bridge, while in each case a methylene group in the alkylene bridge of C3_g is replaced by a group R60-CO- to 1 qui 1 in imi of C? _4 ), [b 1 s - (R gO - C 0) -alkylene of C? _4)] imino, (R70 - PO-OR8) to 1 qu i 1 eni mi no of C1-4 or (R70-PO-R9) -alkyleneimino of C? _4, in count Rg to R9 are as defined in the above, a group pyrrolidino, piperidino ohe xa hi dr oa z ep ino, which is substituted in each case by an amino group, C? -4 alkylammo or di- (C? 4) -amino alkyl, and by a group RgC-CO, while Rg is as defined as er. the above, a piperazino or omopperazino group which is substituted at the 4 position by the Rio group and additionally at a cyclic carbon atom by an RgO-CO group, (R70-PO-OR8), (R7O-PO-R9) , RgO-CO alkyl of C? -4, bis - (RgO-CO) - a 1 qu i 1 or of C? _4, R7O PO-OR8) -alkyl of C? -4 or (R7O-PO-R9) -alkyl of C 4 -4, di- (C

1.) -amino alkyl, 1 to 1 car bon i 1-amino of C 4 -4, N- (C 4 alkyl) a 1 q i 1 ca rbon i 1 - ami n 0 of C? -4, alkylsulfonylamino of C? -4, N- (alkyl of C4-4) -alkylsulfonylamino of C? -4, aminosulfor. ilo, C 1-4 alkylaminosulfonyl or di- (C 1-4 alkyl) -aminosulfonyl, or a carbonyl group which is substituted by an alkyleneimino group of 5 to 7 members, while in the alkylene imino groups of 6 to 7 aforementioned members in each cas or a methylene group in the 4-position can be replaced by an oxygen or sulfur atom, by a sulfinyl, sulfonyl, imino or N- (a 1 c) group; uo of C -4) -imino, and R12 signifies a fluorine, a gold, a bromine or an iodine atom, an alkyl group of C 1-4, trifluoromethyl or an alkoxy of C? _4, or two R? 2 groups, if they are joined to adjacent carbon atoms, together they mean a C3-5 alkylene oxide, methylenedioxy or 1,3-butadiene 1,4-ylene, their tautomers, their stereoisomers and their salts ^^^^ _ ^^^^^^^^

2. Bicyclic heterocycles of the general formula I according to claim 1, wherein Ra means a hydrogen atom, R means a phenyl, benzyl or 1-phenylethyl group, wherein the phenyl nucleus is substituted in each case with the groups Ri to R3, while Ri and R2, which may be equal. or different, each means a hydrogen atom, fluorine, chlorine or bromine, a methyl group, trifluoromethyl, ethinyl or ami not a phenyl group, phenoxy, benzylq benzyloxy, or Ri together with R2, if they are attached to carbon atoms adjacent, they mean a group - CE = CH -NH or -CH = N-NH and R means a hydrogen atom, f Jj or, chlorine or bromine, X and Y together signify a bridge -N = C (-AB) -CH = CH-, -CH = NC (-AB) = CH-, -CH = C (-AB) -N = CH-, -CH = CH-C (-AB) = N-, -N = C (-AB) -N = CH- or -CH = NC (-AB) = N-, while the left end of these bridges is linked to position 5 and the right end of these bridges is linked to position 6 of the pyrimidine ring, A means a group - N R4 - a 1 qu i 1 ene of C? -4, -NR4-cyclohexylene, -NR4-cyclohexylene-NH-S02 alkylene of C _. 3, -NR4 - a 1 qu i 1 of C? _3-cic 1 ohe xi 1 e not, -NR4 - cic 1 ohexi 1 en - a 1 qu i 1 e not of C_ | -3 or - NR4 - a 1 qu i 1 en o de C 1 - 3 - c 1 ohex 1 en - a 1 qu i 1 C1-3 ene, while the -NR - portion of the aforementioned groups in each case is linked to the bicyclic heteroaromatic ring and R4 means a hydrogen atom or a methyl group , a group -NR4, the latter being linked to a carbon atom of group B and R4 is as defined above, a group pyrro 1 i di ni 1 enoopi pe ri di ni 1 e not optionally substituted by one or two methyl groups, while in each case the cyclic nitrogen atom of the aforementioned groups is linked to the bicyclic heteroaromatic ring, h. i &h_í? h_i * _ s2 & _ jF_ ^ a pipe ridini group 1 in carb on i 1 ami • alkylene of C? _2, while the cyclic nitrogen atom of the aforementioned group is bonded to the bicyclic heteroaromatic ring, and B means a group RO - CO - a 1 qu i 1 in - N R5, (R70-PO-OR8) -alkylene-NR5 or (R70-PO-R9) - a 1 qu i 1 e-NR5 wherein in each case the alkylene portion, which is straight chain and contains 1 to 4 atoms! of carbon, can be further substituted by one or two alkyl groups of C? _2 or by a group RCO-CO or a group RgO-CO- to 1 qui 1 or of C? -2, while Rs means a hydrogen atom or an alkyl group of C? -4, which may be substituted by a group RgO-CO, R? , R? and Rs, which can be the same < = > or different, in each case, they mean a hydrogen atom, an alkyl group of C? -8, a cyclopentyl group, cyc 1 or enti 1 -methyl 1, cyclohexyl or 1 or hexyl, or a phenyl group optionally substituted by one or two methyl groups, a 5-indanyl group or an optionally substituted benzyl group eij the phenyl portion by one or two methyl groups, and Rg means a methyl or ethyl group, a pyrrolidino or piperidino group, which is substituted on each in the case of a group R60-CO or RgO-CO-alkyl of C? _4 where Rg is as d fine as in the above, a piperazino or homop iperazi group is not substituted in each case in position 4 by the group Rio and is further substituted on a cyclic carbon atom by a group R60-CO or RgO-CO-alkyl of C? _ Where Rg is as dqfine as in the above and Rio means a hydrogen atom, a methyl group or ethyl, a piperazino or homop ip erazi group, which is substituted in each case in the 4 position or a group R 60 - CO - a 1 qu i 1 or of C i _ 4, bis- (RdO-CO) -alkyl of C -4, (R70-PO-OR8) -alkyl of C? _4 or (R70-PO R < alkyl of C? -4 where Rg to Rg are come defined in the above, a pyrrolidinyl or piperidi nyl group substituted in position 1 by the group Rio, which is additionally substituted in each case in a carbon atom by a group RgO-CO or RgO-CO-alkyl of C? _4 where Rg is as defined above, a pyrrolidinyl group, piperidinyl hexahi dr oa ep ini 1 or substituted at position 1 by a group R60-CO- a 1 qu i 1 o of C _.- 4, bis - (RgO - CO) - a 1 q1 ui 1 o of C? _4, (R70- PO-OR8) -alkyl of C? -4 or (R70-PO-R9 alkyl of C? _4 where Rg to R9 are as defined above, a 2-oxo-mo-1-pho group, which may be substituted by one or two methyl groups, a 2-oxo-mo rfo 1 ini 1 o group, which is substituted at the 4-position by a hydrogen atom, by a methyl, ethyl or RgO-CO-C-alkyl group; 4, while Rg is as defined in the foregoing the 2-oxo-mo-1-in-1 or aforementioned groups in each case, are linked to a carbon atom of group A, a cycloalkyl group of Cs- which is substituted by an amino group, alkylamino or of C? -2- or di- alkyl of C? _2) -amino, and by a group RgQ-CO, while Rg is as defined as above, or A and B together mean a group 1 pyrro 1 i di ni 1 oo 1 - piperi di ni 1 or where the two hydrogen atoms of a methylene group are replaced by a straight chain C4-5 alkylene bridge, while each case a methylene group of the alkylene bridge of C4-5 is replaced by a group RgO-CO- a 1 qu i 1 ene of C1-4 imino, where Rg is as defined above, a pyrrolidino or piperidino group which in each case is substituted by a a.ino group, C? _2 alkyloxy or di- (C? -2) alkyl-amino, and by a group RgO-CO, while Rg is as defined above, a piperazino or homop i pe razi group which is substituted in the 4 position by the Rio group, and additionally in a cyclic carbon atom by a group RgO-CO or RgO-CO-a 1 qu i 1 or of C 1 _ where Rg and R? o are like they were defined in the foregoing, a piperazine or homop ip erazi group is not substituted in each case in position 4 by a group R gO-CO-a 1 qu i 1 or of C? _4, bis - (R gO-CO) - a 1 qui 1 o of Ci- 4, R70-PO-OR8) -alkyl of Cx-, R70-P0 R alkyl of C? .4 where Rg 5 R <; they are as defined in the foregoing, or a 2-oxo-mo r f or 1 i no group, which can be substituted by one or two methyl groups, their tautomers, their stereoisomers and their salts.

3. Bicyclic heterocycles of the general formula I according to claim 1, wherein R a is a hydrogen atom, R b means a phenyl, benzyl or 1-phenylethyl group in which the phenyl nucleus is substituted in each case with the groups R 1 to R 3 , while Rx and R2, which may be the same or different, each means a hydrogen, fluorine, chlorine or bromine atom, a methyl, trifluoromethyl, ethynyl or amino group, or Rx together with R2, if they are attached to carbon atoms. adjacent carbon, mean a group -CH = CH-NH and R3 means a hydrogen atom, fl uor, chloro ob romo, X and Y together signify a bridge of -N = C (-AB) -CH = CH-, -CH = NC (-AB) = CH-, -CH = C (-AB) -N = CH-, -CH = CH-C (-AB) = N-, -N = C (-AB) -N = CH - or -CH = NC (-AB) = N-, while ---, 1 a group 1, 4-piperazin-11-ene, this group being linked in each case to a carbon atom of group B, a 1,4-piperazine-1-en-a-1-c-11 ene group of C? 2, the cyclic nitrogen atom of the aforementioned group, being linked to the bicyclic heteroaromatic ring, a -NR4-piperidini 1 ene group, while the -NR4 portion of the aforementioned group is linked to the bicyclic heteroaromatic ring, and the The cyclic nitrogen of the aforementioned group is bonded to a carbon atom of group B, a group -NR4-cyclohexa 1 in car bon i 1 ami, while the -NR4- portion is linked to the bicyclic heteroaromatic ring, and the nitrogen atom of the carbonylamino portion is bonded to a carbon atom of the group a -N R 4 -cyclo 1 hexhex 1 group i 1 amy non-alkylene of C? _2, while the -NR -party is linked to the heteroaromatic ring bicyclic YB means a group R g0-CO-a 1 qu i 1 in -N R5, R70-PO-OR8) -alkylene-NR5 or (R70-PO-R9) - a 1 qu i 1 in -N R5 in where in each case the alkylene portion is «__« linear chain and contains 1 to 4 carbon atoms, while Rs means a hydrogen atom, an alkyl group of C? _2, which may be substituted by a group RgO-CO, Rg, means a hydrogen atom, an alkyl group of C? -8, a cyclopentyl group, cyclohexyl, ix, cyclohexyl, 111 ooci 1 ohe xylmethyl, a phenyl group optionally substituted by one or two methyl groups, a group 5-indanyl or a benzyl group optionally substituted on the phenyl portion by one or two methyl groups, and R7, R8 and R9, which may be the same or different, in each case mean a methyl or ethyl group, a pyrrolidino or piperidino group, which is substituted in each case by a group RgO-CO or RgO-CO-alkyl of C? _2, wherein R6 is as defined above, a piperazino group, which is substituted at position 4 by a group R gO - CO - a 1 qu i 1 o of C? _3, R70-PO-OR8) alkyl of C? _3, or (R7 O - PO - R9) - a 1oju i 1 o of C? -3, where e Rg to R9 are as defined above, and a pyrrolidinyl, piperidinyl oohe xa hydr or z ep ini 1 group or substituted at position 1 by a group R60-CO-alkyl of C _. 4, bis- (RgO -CO) -alkyl of C? -4, (R7O-PO-0R8) -alkyl of C? _4 or (R70-PO R9) -alkyl of C? -4, where Rg to Rg are comp defined in the above, a 2-oxo-morpholino group, which may be substituted by one or two methyl groups, or A and B together mean a group or 1-p 1 rro 1 i di ni 1 oo 1 -piperi di ni 1 or, where the two hydrogen atoms of a 1-methylene group are replaced by a straight-chain C 4 5 alkylene bridge, while each case a gr up or methylene in the alkylene bridge of C 4-5 is replaced by a group RgO-CO- a 1 qu i 1 en imi nod < ! Cl-2 wherein Rg is as defined above, a piperidino group which is substituted by an amino group and by a group RgO-CO, while Rg is as defined above, a piperazino group, which is substituted at position 4 by a group RgO-CO- at 1 qu 11 or C1-4, where Rg is as defined above, or a 2-oxo-mo-1-pho-1 group, which may be substituted by one or two methyl groups, R 3 signifies a hydrogen atom, fluorine, chlorine ob romo , X and Y together signify a bridge -N = Q (-AB) -N = CH-, while the left end of this bridge is linked to position 5, and the right end of this bridge is linked to position 6 of the pyrimidine ring, A means a group - NR4 - a 1 qu i 1 e not of C? _3, -NR4-cic 1 oh exi 1 ene or - N R4 - cic 1 hexhex 1 in - NHTS 02 - ethylene, while the portion -NR4- of the aforementioned groups in each case is linked to the bicyclic heteroaromatic ring, and R means a hydrogen atom 9 a methyl group, a group -NR, the latter being linked to a carbon atom of group B and R4 it is as defined in the foregoing, a group pyrro 1 i di ni 1 e not op ipe ri di ni 1 e not optionally substituted by a methyl group, m whereas in each case the cyclic nitrogen atom of the aforementioned groups is linked to the bicyclic heteroaromatic artillo, * __ "_, _..._. A group piperidini 1 e nme ti 1 ene, while the cyclic nitrogen atom is linked to the bicyclic heteroaromatic ring, a group 1, 4-p ipe razini 1 eno, this group is linked to a carbon atom of group B, and B means a group RgO-CO-a 1 qu i 1 en-1JJ R 5 -, wherein the alkylene portion is straight chain and contains 1 to 4 carbon atoms, while Rs means a hydrogen atom, an alkyl group of C? -2, which may be substituted by a group RgO-CO-, Rg signifies a hydrogen atom, an alkyl group of C 1-4, cyclohexyl, phenyl, benzyl or 5-indanyl, a pyrrolidino or piperidino group, which is substituted in each case by a group R60-CO or RgO-CO-C-2 alkyl, while Rg is comf is defined as in the above, a piperazino group , which is substituted at position 4 by a group RgO-CO -me ti 1 oo (R7O-PO-OR8) -methyl, where Rg is as defined as before above, and R7 and R8 in each case mean a methyl or ethyl group, _tf___l___ii____________? ____a___ a piperidinyl group substituted e? position 1 by a group RgO-CO- a 1 qui 1 or of C i _ 4, bis- RgO-CO) -alkyl of C? _4, (R70-PO-OR8) -methyl or (R70-PO-R8 ) -ethyl, (R7O-PO-R9) -methyl, wherein R6 to R1 are as defined in the above and R9 means a methyl or ethyl group, a 2-ox or -mo-1-ino-group, which can to be substituted by one or two methyl groups or A and B together mean a r up or piperidino which is substituted by an amino group and by a group R60-C0, while Rg is as defined above, a piperazino group , which is substituted in position 4 by a group RgO-CO- a 1 qu i 1 or of C 1 - 2, where Re is as defined as in the foregoing, its tautomers, its stereoisomers and its salts. 6. The following compounds of the form mu 1 to general I according to claim 1 (1) 4- [(3-chloro-4-fluoro-phenyl) amino] "6 (. {1- [(methoxycarbonyl)] methyl] -piperidin-4-? l.}. amin pyrimido [5, 4 d] pyrimidine, 2) 4 - [(3-chloro-4-fluoro-phenyl) amino [(trans-4- {N- [(methoxycarbonyl) methyl] -N-methylamino or -cyclohex-1-yl) amino] -pyrimido [5, 4-d] pyrimidine, and ^ s ^ r (3) 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4 ( { N - [(methoxycarbonyl) methyl] -N-methylamino] methyl) piperidine- 1-yl] -pyrimido- [5, 4-d] pyrimidine, (4) 4 - [(3-bromophenyl) amino] -6- | (. {L- [(methoxycarbonyl) methyl] -piperidin-4-) il.} amino) -pyrimido [5, 4-d] pyrimidine, (5) 4- [(3-chlorophenyl) amino] -6- (. {l- [(methoxycarbonyl) methyl] -piperidin-4-) il.} amino) -pyrimido [5, 4-d] pyrimidine, (6) 4- [(3-methylphenyl) amino] -6- (. {1 - [(methoxycarbonyl) methyl] -piperidin-4-) il.} amino) -pyrimido [5, -d] pyrimidine, (7) 4- [(4-Amino-3,5-dichlorofenyl) amino] -6 - (. {1- [(methoxycarbonyl) methyl] ] -piperidin-4-yl.}. amino) -pyrimid [5, 4-d] pyrimidin, (8) 4- [(4-amino-3,5-d? bromofenyl) amino] - 6 - ( { 1- [(Methoxycarbonyl) methyl] -piperidin-4-yl) amino) -pyrimido [5, -d] pyrimidine, (9) 4- [(Indol-5-yl) amino] - 6- ( { 1- [(methoxycarbonyl) methyl] -piperidin-4-yl} amino) -pyrimido [5, 4-d] pyrimidine, (10) 4- [(3-chloro-4 -fluorine ofenyl) amino] -6- [(trans-4-. { N, N-bis- [ethoxycarbonyl) ethyl] amino} cyclohex-1-yl) amino] -pyrimido [5, -d] pyrimidine, ^^^^ ^ ^^ 19) 4 - [(3-chloro-4-fluorophenyl) amin ©] -6-. { [trans-4- (2-oxo-morpholin-4-yl) -cyclohex-1-yl] -amino} -pyrimido [5, 4-d] pyrimidine and its salts. 7. Physiologically acceptable salts of the compounds according to claims 1 to 6 with inorganic or organic acids or bases. Pharmaceutical compositions containing a compound according to claims 1 to 6 or a physiologically acceptable salt according to claim 7, optionally, together with one or more inert carriers and / or diluents. 9. Use of a compound according to at least one of claims 1 to 7 for preparing pharmaceutical compositions that are suitable for the treatment of benign or malignant tumors, for the prevention and treatment of diseases of the respiratory tract and of the lungs, for the treatment of polyps, diseases of the gastrointestinal tract, bile ducts and gallbladder, as well as the kidneys and the skin. 10. Procedure for preparing a pharmaceutical composition in accordance with -i-Claim 8, characterized in that a compound according to at least one of the r e i vi nd i c a c 4- one s 1 to 7, is incorporated in one or more infrequent carriers and / or diluents by a non-chemical method. 11. Process for preparing the compounds of the general formula I according to claims 1 to 7, characterized in that a) a compound of the general formula R. wherein Ra and Rb are as defined in claims 1 to 6, X 'and Y' together denote a bridge -N = CZ? -CH = CH-, -CH = N-CZ? = CH-, -CH = CZ? -N = CH-, -CH = CH-CZ? = N-, -N = CZX-N = CH- or -CH = N-CZ? = N-, where Zi means an exchangeable group is reacted with a compound of the mu mu 1 to general H-A-B, (III) wherein A and B are as defined in rei indications 1 to 6, or b) to prepare a compound of the general mule form I where at least one of the groups R, Rg means a hydrogen atom: a compound of the general formula R * Rb wherein Ra and Rb are as defined in claims 1 to 6, X "and Y" together signify a bridge -N = C (-AB ') -CH = CH-, -CH = NC (-AB') = CH-, -CH = C (-AB ') -N = CH-, -CH = CH-C (-AB') = N-, -N = C (-AB ') -N = CH- or -CH = NC (-AB ') = N-, where i? zy &? JA -. ??,. - "_" «i -« _ £ «_ __a-ci_a __¡_É _______ li__ A is defined as in the claims is 1 to 6 and B 'has the meanings given for B in claims 1 to 6, with the condition that B 'contains a group RgO-CO, (R70-PO-OR8) or (R7Q -PO-Rg), where R9 is defined as in rei indications 1 to 6 and at least one of the groups Rg to Rs does not represent a hydrogen atom is converted by hydrolysis, acid treatment, thermolysis or hydrogenolysis, into a compound of the general formula I wherein at least one of the groups R6 to R8 means a hydrogen atom, or c) to prepare a compound of the general formula I wherein A means a NR4-cycloalkylene group of C4 -7-NH2-S2-CH2CH2 or TNR4 cyc1 or 1 to 1 in i of C4-7-N (alkyl of C? _4) - S 02 - CH2 Cf H2 and B means a group RgO-CO - a 1 qu i 1 e not of Ci- -NRs, while R4 to Rg are as defined in claims 1 to 6: a compound of the general formula wherein Ra and Rb are as defined in claims 1 to 6, X "'and Y"' together signify a bridge -N = C (-A '-H) -CH = CH-, -CH = NC (- A '-H) = CH-, -CH = C (-A' -H) -N = CH-, -CH = CH-C (-A '-H) = N-, -N = C (-A '-H) -N = CH- or -CH = NC (-A' -H) = N-, where A 'means a group - N R4 - cic 1 or 1 quinol of C? -7- NH-S02-CH = CH2 or - NR 4 - cyc 1 or 1 to 1 to C 4 -7 - N (a 1 qu i 1 or of C 1 _ 4) - S O2 - CH = CH 2, while 1 4 is as defined in claims 1 to 6 is reacted with a compound of the general formula R 6 O -CO-alkylene of C, .6-NHR 5, (VI) wherein R 5 and R 6 are as defined in claims 1 to 6, or d to prepare a compound of the general formula I, wherein B means a group R -C0-a 1 qu 11 in -NR5, wherein the alkylene portion, qu is straight chain and contains 1 to 6 carbon atoms, may be further substituted by one or two C1-2 alkyl groups or by a group for R60-CO or RgO-CO-a 1 qu i 1 or for C? -2, a piperazi nouh omop ip erazi group not substituted in position 4 by a group Rs0 - CO- a 1 qu i 1 of C ? - obis - (RgO- CO) - at 1 q of C1-4, or a pyrrolidinyl group, pi pe ri di ni JL oo he xah i dr or z ep ini 1 o substituted at position 1 by a group RgO - CO- to 1 qui 1 of C? _ Obis - (RgO-CO) -alkyl of C 1 _ 4, while in each case R5 and Rg are as defined in claims 1 to 6: a compound of the General Formula wherein Ra and Rb are as defined in claims 1 to 6, X "" e? p "together means a bridge - N = C (- A - B") - CH = CH -, - CH = NC - - AB ") = CH-, -CH = C (-AB") -N = CH-, -CH = CH-C (-AB ") = N-, -N = C (-AB") - N = CH - or -CH = NC (-AB ") = N-wherein A is defined as in the claims is 1 to 6 and B "means a group R5NH, wherein R 5 is defined as in claims 1 to 6, a piperazino or homopiperazi group not unsubstituted in position 4, a pyrro group 1 i di n 11 o, piperidinyl ohe xa hi dr oa z ep ini 1 o unsubstituted at position 1, is reacted with a compound of the general formula R60-CO-alkylene-Z2, (V 111) wherein the alkylene portion, which is straight chain and contains 1 to 6 carbon atoms, can be further substituted by one or two C? -2 alkyl groups or by a RgO-CO or RgO-CO-alkyl group of C? _2, while Rg in each case is as defined in claims 1 to 6, and Z2 signifies an exchangeable group, oe) to prepare a compound of general form I, where B means a group (R7) PO-OR8) -CH2-NR5 or (R70-PO-R9) -CH2-NR5, a piperazino or homopipera z 1 group unsubstituted in the 4 position by a group (R 70-PO-OR8) -CH2 or (R70-PO-R9) -CH2, or a pyrrolidir group. i 1, piperidinyl or hexahi dr oa z epi ni 1 or substituted at position 1 by a group (R70-PO-OR8) - CH2 or (R7 -PO-Rg) -CH2, while in each case R5 and R ? R are as defined in claims 1 to 6: a compound of the general formula wherein Ra and Rb are as defined in claims 1 to 6, X "" e? "together signify a bridge - N = C (-AB") -CH = CH-, -CH = NC (-AB ") = CH-, -CH = C (- A - B") -N = CH-, -CH = CH-C (-AB ") = N-, -N = C (-AB") - N = CH- or -CH = NC (-AB ") = N-, where A is defined as the claim is 1 to 6 and B "means a group R5NH, wherein F. 5 is defined as in claims 1 to 6, a? -r upo piperazino uh omop iperazi not unsubstituted and ñ the position 4, a pyrrolidinyl group , piperidini lo ohe xa hi dr oa z ep ini 1 or unsubstituted in position 1, is reacted with formaldehyde or one of its derivatives and a compound of the general formula H- (R7O) PO (OR8), (IX ) or C1.4-P alkoxy (R7O) (R9), (X) wherein R7 to Rg are as defined in claims 1 to 6, of) To prepare a compound of the form mu 1 to general I, wherein B means a group RgC -CO- CH2CH2-NR5, wherein the portion of -CH2CH2- may be substituted by one or two alkyl or C1-2 groups or by a group R60-CO or R60-CO- a 1 qu i 1 of Ci - 2 1 a piperazino or homopipera zi group not substituted at the 4 position by a group RgC -CO- CH2CH2, wherein the portion of -CH2CH2- can be further substituted in each case by a gr up or R60-C0 or RgO- CO- alkyl of C _._ 2, or Ri__É_Mk ___? Mi__á_li ___ ii_______riH ll_ £ li_ÜIIMlÉ ___ E__ a pyrrolidinyl, piperidinyl or hexahydride or z ep ini 1 o substituted in the 1-position by a group RgO-CO-CH2CH2, where the portion of -CH2CH2- can be substituted in each case by di ci ona It is defined by a group R60-CO or RgO-CO- a 1 qu i 1 or C? -2, and Rs and Rg in each case are defined as in claims 1 to 6: a compound of the general formula wherein Ra and Rb are as defined in claims 1 to 6, X "" and Y "" together signify a bridge -N = C (-AB ") -CH = CH-, -CH = NC (-AB" ) = CH-, -CH = C (-AB ") - N = CH-, -CH = CH-C (-AB") = N-, -N = C (-AB ") - N = CH- or -CH = NC (-AB ") = N-, where A is defined as in claim 6 and ___ t_á_ ^ ÍH¡_¡__MH_l__ B "means a group R5NH, wherein R5 is defined as in claims 1 to 6, a piperazino group uh omop iperazino without replacing at position 4, a piπrol idini 1 group, pipepdinilo or where xahi dr or z ep ini 1 or unsubstituted in position 1, is reacted with an acrylate of the general formula CH = CH-CO-OR,, (X ") where the vinyl portion can be substituted! by one or two alkyl groups of C? _2 or by a group RIgO-CO or RgO-CO-a 1 qui 1 or of C _.- 2, and Rg in each case are defined as in claims 1 to 6, or .) a compound of the general formula I where it means a piperidinyl group substituted at the 1-position by a group (R7 O-PO-OR8) - C H2 CH i: a corresponding compound of the pommu 1 a general I containing a piperidinyl group s 1 n substituting in the I position is reacted with a corresponding vinylphosphonic acid derivative, and subsequently, if desired, a compound of the general formula I thus obtained which contains a carboxy or hydroxyl group ifosphoric acid 1 or is converted by esterification into a corresponding ester of the general formula I and / or ____________ttl __ ^ a compound of the general formula l | thus obtained wherein B means an optionally substituted N- (2-hydroxyethyl) -glycine ester group; converted by cyclization to a compound 2-oxo morpholino co r r e s in t e y / o | if necessary, any pro-4-yy group used during the reactions described above is redoubled and / or if a compound of the general formula I thus obtained is resolved in its stereoisomer and / or a compound of the formula In general, I thus obtained becomes its salt, more particularly I, for pharmaceutical use in its physiologically acceptable salts. djÉiiii ^ u ^ _ ^ ^ k ____ to _____________________? ________?