RU98118380A - PYRAMIDO [5,4-D] PYRIMIDINES CONTAINING THESE COMPOUNDS MEDICINES, THEIR USE AND METHOD FOR PRODUCING THEM - Google Patents
PYRAMIDO [5,4-D] PYRIMIDINES CONTAINING THESE COMPOUNDS MEDICINES, THEIR USE AND METHOD FOR PRODUCING THEMInfo
- Publication number
- RU98118380A RU98118380A RU98118380A RU98118380A RU98118380A RU 98118380 A RU98118380 A RU 98118380A RU 98118380 A RU98118380 A RU 98118380A RU 98118380 A RU98118380 A RU 98118380A RU 98118380 A RU98118380 A RU 98118380A
- Authority
- RU
- Russia
- Prior art keywords
- group
- amino
- substituted
- pyrimido
- chloro
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims 23
- 239000003814 drug Substances 0.000 title claims 3
- 238000004519 manufacturing process Methods 0.000 title 1
- 150000003230 pyrimidines Chemical class 0.000 title 1
- -1 cyano - Chemical class 0.000 claims 366
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 22
- 125000003277 amino group Chemical group 0.000 claims 19
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 19
- 125000000217 alkyl group Chemical group 0.000 claims 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 16
- JOZPEVMCAKXSEY-UHFFFAOYSA-N pyrimido[5,4-d]pyrimidine Chemical class N1=CN=CC2=NC=NC=C21 JOZPEVMCAKXSEY-UHFFFAOYSA-N 0.000 claims 16
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims 15
- 125000003282 alkyl amino group Chemical group 0.000 claims 14
- 125000004432 carbon atom Chemical group C* 0.000 claims 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 11
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 11
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 11
- 150000003839 salts Chemical class 0.000 claims 11
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 10
- 125000004663 dialkyl amino group Chemical group 0.000 claims 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 10
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 10
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 10
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 9
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 8
- 125000001841 imino group Chemical group [H]N=* 0.000 claims 8
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 8
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 6
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 6
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims 5
- 229910052757 nitrogen Inorganic materials 0.000 claims 5
- 229910052760 oxygen Inorganic materials 0.000 claims 5
- 239000001301 oxygen Substances 0.000 claims 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 5
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 4
- 125000003545 alkoxy group Chemical group 0.000 claims 4
- 125000004429 atom Chemical group 0.000 claims 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 4
- 125000006626 methoxycarbonylamino group Chemical group 0.000 claims 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 4
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims 3
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims 3
- 125000005237 alkyleneamino group Chemical group 0.000 claims 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims 3
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 3
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims 3
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims 3
- 239000001257 hydrogen Substances 0.000 claims 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 3
- 229910052717 sulfur Inorganic materials 0.000 claims 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 2
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 2
- VYIISGRSCFDALJ-UHFFFAOYSA-N 4-n-(6-morpholin-4-ylpyrimido[5,4-d]pyrimidin-4-yl)-2-nitrobenzene-1,4-diamine Chemical compound C1=C([N+]([O-])=O)C(N)=CC=C1NC1=NC=NC2=CN=C(N3CCOCC3)N=C12 VYIISGRSCFDALJ-UHFFFAOYSA-N 0.000 claims 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 2
- HDBREMCJUIQJGV-HOMQSWHASA-N C1=C(Cl)C(N)=C(Cl)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](O)CC1 Chemical compound C1=C(Cl)C(N)=C(Cl)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](O)CC1 HDBREMCJUIQJGV-HOMQSWHASA-N 0.000 claims 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 2
- NJHIXVCSVBZKRX-UMSPYCQHSA-N ClC1=C(C=C(C=C1)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)O)[N+](=O)[O-] Chemical compound ClC1=C(C=C(C=C1)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)O)[N+](=O)[O-] NJHIXVCSVBZKRX-UMSPYCQHSA-N 0.000 claims 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- XWJDVVZLQSQCAV-UMSPYCQHSA-N Nc1ccc(Nc2ncnc3cnc(N[C@H]4CC[C@H](O)CC4)nc23)cc1[N+]([O-])=O Chemical compound Nc1ccc(Nc2ncnc3cnc(N[C@H]4CC[C@H](O)CC4)nc23)cc1[N+]([O-])=O XWJDVVZLQSQCAV-UMSPYCQHSA-N 0.000 claims 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 2
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 2
- 239000000969 carrier Substances 0.000 claims 2
- 239000000460 chlorine Substances 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 2
- 125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 2
- 239000011737 fluorine Substances 0.000 claims 2
- 229910052731 fluorine Inorganic materials 0.000 claims 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 2
- 230000003993 interaction Effects 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims 2
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims 2
- DTNQTMAGMDRICO-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-[4-(1-methylpiperidin-4-yl)piperidin-1-yl]pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1CN(C)CCC1C1CCN(C=2N=C3C(NC=4C=C(Cl)C(F)=CC=4)=NC=NC3=CN=2)CC1 DTNQTMAGMDRICO-UHFFFAOYSA-N 0.000 claims 2
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 2
- 125000004434 sulfur atom Chemical group 0.000 claims 2
- RPSYMAMREDJAES-NTSWFWBYSA-N (2r,5s)-2,5-dimethylmorpholine Chemical group C[C@H]1CO[C@H](C)CN1 RPSYMAMREDJAES-NTSWFWBYSA-N 0.000 claims 1
- NDZPCTMEAPKWLH-UHFFFAOYSA-N 1-[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]piperidin-4-ol Chemical compound C1CC(O)CCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 NDZPCTMEAPKWLH-UHFFFAOYSA-N 0.000 claims 1
- 125000004486 1-methylpiperidin-3-yl group Chemical group CN1CC(CCC1)* 0.000 claims 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- PXHFWPOPKVWXQT-UHFFFAOYSA-N 3-methyl-1h-imidazol-2-one Chemical compound CN1C=CN=C1O PXHFWPOPKVWXQT-UHFFFAOYSA-N 0.000 claims 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- BFTYQYYBQNXKDS-UHFFFAOYSA-N 4-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]-n,n-dimethylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)N(C)C)CCC1NC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 BFTYQYYBQNXKDS-UHFFFAOYSA-N 0.000 claims 1
- DSJNHTGFNMAKQS-UHFFFAOYSA-N 4-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]piperidine-1-carbonitrile Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NC1CCN(C#N)CC1 DSJNHTGFNMAKQS-UHFFFAOYSA-N 0.000 claims 1
- OSTDHUNARBLCPT-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-(1-methylpiperidin-3-yl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1N(C)CCCC1NC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 OSTDHUNARBLCPT-UHFFFAOYSA-N 0.000 claims 1
- DUIDQEZCITUJOU-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-(2-piperazin-1-ylethyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NCCN1CCNCC1 DUIDQEZCITUJOU-UHFFFAOYSA-N 0.000 claims 1
- YCKBKLQNSNOZCC-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-(3-morpholin-4-ylpropyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NCCCN1CCOCC1 YCKBKLQNSNOZCC-UHFFFAOYSA-N 0.000 claims 1
- YYHURUCEAOGAFA-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-(4-morpholin-4-ylcyclohexyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NC1CCC(N2CCOCC2)CC1 YYHURUCEAOGAFA-UHFFFAOYSA-N 0.000 claims 1
- ZDCCULNSINBBDM-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-(piperidin-4-ylmethyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NCC1CCNCC1 ZDCCULNSINBBDM-UHFFFAOYSA-N 0.000 claims 1
- UIYDNRPJDAKFEE-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-[(1-methylpiperidin-4-yl)methyl]pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1CN(C)CCC1CNC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 UIYDNRPJDAKFEE-UHFFFAOYSA-N 0.000 claims 1
- RVBKCXFOUAMDGX-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-[4-(4-methylpiperazin-1-yl)cyclohexyl]pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1CN(C)CCN1C1CCC(NC=2N=C3C(NC=4C=C(Cl)C(F)=CC=4)=NC=NC3=CN=2)CC1 RVBKCXFOUAMDGX-UHFFFAOYSA-N 0.000 claims 1
- SBRKZTRZGNOWNH-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-methyl-6-n-(1-methylpiperidin-4-yl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound N=1C=C2N=CN=C(NC=3C=C(Cl)C(F)=CC=3)C2=NC=1N(C)C1CCN(C)CC1 SBRKZTRZGNOWNH-UHFFFAOYSA-N 0.000 claims 1
- LHMSGUCCOMYASZ-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-6-n-piperidin-3-ylpyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NC1CNCCC1 LHMSGUCCOMYASZ-UHFFFAOYSA-N 0.000 claims 1
- IDURNBGPECAQTH-UHFFFAOYSA-N 6-(3-aminopiperidin-1-yl)-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1C(N)CCCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 IDURNBGPECAQTH-UHFFFAOYSA-N 0.000 claims 1
- LWAQHCQLCICHJH-UHFFFAOYSA-N 6-(3-aminopyrrolidin-1-yl)-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1C(N)CCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 LWAQHCQLCICHJH-UHFFFAOYSA-N 0.000 claims 1
- JKWQTABCEDZHMO-UHFFFAOYSA-N 6-(4-amino-4-methylpiperidin-1-yl)-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1CC(C)(N)CCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 JKWQTABCEDZHMO-UHFFFAOYSA-N 0.000 claims 1
- VORHRQJEKLYXKI-UHFFFAOYSA-N 6-(4-aminoazepan-1-yl)-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1CC(N)CCCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 VORHRQJEKLYXKI-UHFFFAOYSA-N 0.000 claims 1
- RYWBCODYRUCURN-UHFFFAOYSA-N 6-(4-aminopiperidin-1-yl)-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1CC(N)CCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 RYWBCODYRUCURN-UHFFFAOYSA-N 0.000 claims 1
- OULCPNGKXGXZIG-UHFFFAOYSA-N 6-[3-(aminomethyl)piperidin-1-yl]-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1C(CN)CCCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 OULCPNGKXGXZIG-UHFFFAOYSA-N 0.000 claims 1
- FPYLEGNPEQPDQD-UHFFFAOYSA-N 6-[4-(2-aminoethyl)piperazin-1-yl]-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1CN(CCN)CCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 FPYLEGNPEQPDQD-UHFFFAOYSA-N 0.000 claims 1
- XLGCTOXPKQVOOU-UHFFFAOYSA-N 6-[4-(aminomethyl)piperidin-1-yl]-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1CC(CN)CCN1C1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 XLGCTOXPKQVOOU-UHFFFAOYSA-N 0.000 claims 1
- REAQUNXUWXXIIU-UHFFFAOYSA-N 6-n-(1-azabicyclo[2.2.2]octan-3-yl)-4-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NC1C(CC2)CCN2C1 REAQUNXUWXXIIU-UHFFFAOYSA-N 0.000 claims 1
- LEUJFISHIOATTG-UHFFFAOYSA-N 6-n-(1-azabicyclo[2.2.2]octan-4-ylmethyl)-4-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NCC1(CC2)CCN2CC1 LEUJFISHIOATTG-UHFFFAOYSA-N 0.000 claims 1
- GJMXSLKSMVMHQM-UHFFFAOYSA-N 6-n-(2-amino-2-methylpropyl)-4-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C12=NC(NCC(C)(N)C)=NC=C2N=CN=C1NC1=CC=C(F)C(Cl)=C1 GJMXSLKSMVMHQM-UHFFFAOYSA-N 0.000 claims 1
- BQGLCJRNQGJBTC-UHFFFAOYSA-N 6-n-(3-aminopropyl)-4-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C12=NC(NCCCN)=NC=C2N=CN=C1NC1=CC=C(F)C(Cl)=C1 BQGLCJRNQGJBTC-UHFFFAOYSA-N 0.000 claims 1
- OWIRUOISYWMKMA-UHFFFAOYSA-N 6-n-[(4-aminophenyl)methyl]-4-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1=CC(N)=CC=C1CNC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 OWIRUOISYWMKMA-UHFFFAOYSA-N 0.000 claims 1
- KPZKEICOCNZRSE-UHFFFAOYSA-N 6-n-[[3-(aminomethyl)cyclohexyl]methyl]-4-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1C(CN)CCCC1CNC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 KPZKEICOCNZRSE-UHFFFAOYSA-N 0.000 claims 1
- PDCRNLOZPXMCER-UHFFFAOYSA-N 6-n-[[4-(aminomethyl)cyclohexyl]methyl]-4-n-(3-chloro-4-fluorophenyl)pyrimido[5,4-d]pyrimidine-4,6-diamine Chemical compound C1CC(CN)CCC1CNC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 PDCRNLOZPXMCER-UHFFFAOYSA-N 0.000 claims 1
- SHYIUIWRSJPFDA-HZCBDIJESA-N C(C1=CC=CC=C1)OC1=CC=C(C=C1)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)N(C)C Chemical compound C(C1=CC=CC=C1)OC1=CC=C(C=C1)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)N(C)C SHYIUIWRSJPFDA-HZCBDIJESA-N 0.000 claims 1
- XBARGVDOISHQKQ-HOMQSWHASA-N C1=C(Br)C(N)=C(Br)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](O)CC1 Chemical compound C1=C(Br)C(N)=C(Br)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](O)CC1 XBARGVDOISHQKQ-HOMQSWHASA-N 0.000 claims 1
- LZFHYLOIDMZADK-QAQDUYKDSA-N C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](CCC(=O)N2CCOCC2)CC1 Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](CCC(=O)N2CCOCC2)CC1 LZFHYLOIDMZADK-QAQDUYKDSA-N 0.000 claims 1
- GYJZOWPUMTUSEE-HDJSIYSDSA-N C1=C(Cl)C(N)=C(Cl)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](C(=O)N2CCOCC2)CC1 Chemical compound C1=C(Cl)C(N)=C(Cl)C=C1NC(C1=N2)=NC=NC1=CN=C2N[C@@H]1CC[C@@H](C(=O)N2CCOCC2)CC1 GYJZOWPUMTUSEE-HDJSIYSDSA-N 0.000 claims 1
- HGFKQQJZAJZDRG-HAQNSBGRSA-N ClC=1C=C(C=CC1F)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)CN Chemical compound ClC=1C=C(C=CC1F)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)CN HGFKQQJZAJZDRG-HAQNSBGRSA-N 0.000 claims 1
- 206010027476 Metastases Diseases 0.000 claims 1
- VFCBLKHHSOCJBA-HDJSIYSDSA-N NC1=C(C=C(C=C1Cl)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)C(=O)N2CCCC2)Cl Chemical compound NC1=C(C=C(C=C1Cl)NC=1C2=C(N=CN1)C=NC(=N2)N[C@@H]2CC[C@H](CC2)C(=O)N2CCCC2)Cl VFCBLKHHSOCJBA-HDJSIYSDSA-N 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 206010029113 Neovascularisation Diseases 0.000 claims 1
- KMHLXHOWFPMNMT-UHFFFAOYSA-N [4-[2-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]ethyl]piperazin-1-yl]-morpholin-4-ylmethanone Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2NCCN1CCN(C(=O)N2CCOCC2)CC1 KMHLXHOWFPMNMT-UHFFFAOYSA-N 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 claims 1
- 125000002252 acyl group Chemical group 0.000 claims 1
- 230000010933 acylation Effects 0.000 claims 1
- 238000005917 acylation reaction Methods 0.000 claims 1
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims 1
- 230000029936 alkylation Effects 0.000 claims 1
- 238000005804 alkylation reaction Methods 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 230000009435 amidation Effects 0.000 claims 1
- 238000007112 amidation reaction Methods 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 150000001728 carbonyl compounds Chemical class 0.000 claims 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 claims 1
- 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims 1
- 125000004188 dichlorophenyl group Chemical group 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 125000004185 ester group Chemical group 0.000 claims 1
- 230000032050 esterification Effects 0.000 claims 1
- 238000005886 esterification reaction Methods 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 230000009401 metastasis Effects 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- BJIQQSGPZKGUAE-UHFFFAOYSA-N methyl 4-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC)CCC1NC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 BJIQQSGPZKGUAE-UHFFFAOYSA-N 0.000 claims 1
- GFKYMYYJOGXQBW-UHFFFAOYSA-N methyl n-[3-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]propyl]carbamate Chemical compound C12=NC(NCCCNC(=O)OC)=NC=C2N=CN=C1NC1=CC=C(F)C(Cl)=C1 GFKYMYYJOGXQBW-UHFFFAOYSA-N 0.000 claims 1
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- ZJUBWLYEKZUHOB-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-(4-morpholin-4-ylpiperidin-1-yl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CN=C(N3CCC(CC3)N3CCOCC3)N=C12 ZJUBWLYEKZUHOB-UHFFFAOYSA-N 0.000 claims 1
- FPZZRINZZMYKHL-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-(4-piperidin-4-ylpiperidin-1-yl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CN=C(N3CCC(CC3)C3CCNCC3)N=C12 FPZZRINZZMYKHL-UHFFFAOYSA-N 0.000 claims 1
- DNMZGZNLNVVEHS-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-(4-pyrrolidin-1-ylpiperidin-1-yl)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CN=C(N3CCC(CC3)N3CCCC3)N=C12 DNMZGZNLNVVEHS-UHFFFAOYSA-N 0.000 claims 1
- OMVYAPIWXONNFV-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-(oxan-4-yloxy)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2OC1CCOCC1 OMVYAPIWXONNFV-UHFFFAOYSA-N 0.000 claims 1
- JGNKOJPHBUJTJZ-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-(oxolan-3-yloxy)pyrimido[5,4-d]pyrimidin-4-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=N2)=NC=NC1=CN=C2OC1COCC1 JGNKOJPHBUJTJZ-UHFFFAOYSA-N 0.000 claims 1
- BJEGBURCEKGQDB-UHFFFAOYSA-N n-[1-[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]piperidin-4-yl]formamide Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CN=C(N3CCC(CC3)NC=O)N=C12 BJEGBURCEKGQDB-UHFFFAOYSA-N 0.000 claims 1
- TWPVDIOCVXCQIV-UHFFFAOYSA-N n-[4-[[4-(3-chloro-4-fluoroanilino)pyrimido[5,4-d]pyrimidin-6-yl]amino]cyclohexyl]-n-methylacetamide Chemical compound C1CC(N(C)C(C)=O)CCC1NC1=NC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=N1 TWPVDIOCVXCQIV-UHFFFAOYSA-N 0.000 claims 1
- 125000004888 n-propyl amino group Chemical group [H]N(*)C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 235000005985 organic acids Nutrition 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 claims 1
- 230000035755 proliferation Effects 0.000 claims 1
- 125000006239 protecting group Chemical group 0.000 claims 1
- 238000005932 reductive alkylation reaction Methods 0.000 claims 1
- 239000010802 sludge Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 230000006103 sulfonylation Effects 0.000 claims 1
- 238000005694 sulfonylation reaction Methods 0.000 claims 1
- 230000009466 transformation Effects 0.000 claims 1
- 238000000844 transformation Methods 0.000 claims 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 210000003556 vascular endothelial cell Anatomy 0.000 claims 1
Claims (12)
где Ra означает атом водорода; Rb означает фенильную группу, замещенную остатками от R1 до R3, которые могут быть одинаковыми или разными, причем R1 означает атом водорода, фтора, хлора или брома, трифторметоксигруппу, метильную, гидроксиметильную, трифторметильную, этинильную группу, нитро-, циано-, феноксигруппу, фенильную группу, бензилоксигруппу, бензильную группу, 1,1,2,2-тетрафторэтокси- или метоксигруппу, R2 означает атом водорода, амино-, метиламино- или диметиламиногруппу и R3 означает атом водорода, фтора, хлора или брома; или Ra и Rb вместе с находящимся между ними атомом азота означают индолин-1-ильную или 1,2,3,4-тетрагидрохинолин-1-ильную группу; и Rc означает циклопентилоксигруппу, в которой метиленовая группа в положении 3 заменена атомом кислорода или N-алкилиминогруппой; циклогексилоксигруппу, в которой метиленовая группа в положении 4 заменена атомом кислорода или N-алкилиминогруппой; пирролидин-1-ильную группу, которая в положении 3 замещена амино-, алкиламино-, диалкиламиногруппой или 4-гидроксифенильной группой и возможно дополнительно метильной группой; пиперидин-1-ильную группу, которая может быть замещена аминометильной, алкиламинометильной, диалкиламинометильной, (пирролидин-1-ил)метильной, (пиперидин-1-ил)метильной, (пиперазин-1-ил)метильной, (4-метилпиперазин-1-ил)метильной, морфолинометильной, алкилкарбониламинометильной, алкилсульфониламинометильной, цианометильной, аминокарбонилметильной, аминокарбонильной, (пиперазин-1-ил)кар6онильной, (4-метилпиперазин-1-ил)карбонильной, 2-карбоксиэтильной, 2-алкоксикарбонилэтильной, 2-(морфолинокарбонил)-этильной, 2-аминоэтильной, 2-аминокарбонилэтильной, 2-алкиламинокарбонилэтильной, 2-диалкиламинокарбонилэтильной, 2-(пирролидин-1-илкар6онил)этильной группой, карбоксиметилоксигруппой, алкоксикарбонилметилоксигруппой, аминокарбонилметилоксигруппой, алкиламинокарбонилметилоксигруппой, диалкиламинокарбонилметилоксигруппой, морфолинокарбонилметилоксигруппой, (пирролидин-1-ил)карбонилметилоксигруппой, пиперидин-4-ильной или 1-метилпиперидин-4-ильной группой; пиперидинил-1-ильную группу, которая в положении 3 или 4 замещена аминогруппой и возможно дополнительно замещена одной или двумя метильными группами или гидроксильной, алкоксильной группой, формиламино-, алкиламино-, диалкиламино-, морфолинокарбониламино-, алкоксикарбониламино-, алкилкарбониламино-, морфолиногруппой, пирролидин-1-ильной, пиперидин-1-ильной, пиперазин-1-ильной, 4-метилпиперазин-1-ильной, 4-диметиламинопиперидин-1-ильной, 4-аминопиперидин-1-ильной, 2-оксопирролидин-1-ильной, 4-гидроксипиперидин-1-ильной, 4-метиламинопиперидин-1-ильной, 3-оксопиперазин-1-ильной, 4-метил-3-оксопиперазин-1-ильной группой, N-ацетил-N-метиламино-, N-метил-N-метилсульфониламиногруппой, 2-оксоимидазолидин-1-ильной или 3-метил-2-оксоимидазолидин-1-ильной группой; 1-азациклогептильную группу, незамещенную или замещенную в положении 3 или 4 аминогруппой, гидроксильной группой, алкоксильной группой, алкиламиногруппой, диалкиламиногруппой, алкоксикарбониламиногруппой или алкилкарбониламиногруппой; незамещенную или замещенную одной или двумя могильными группами морфолиногруппу; пиперазин-1-ильную группу, которая в положении 4 замещена 2-аминоэтильной, 2-алкиламиноэтильной, 2-диалкиламиноэтильной, морфолинокарбонильной или замещенной алкоксигруппой фенильной группой; незамещенную или замещенную в положении 4 алкильной группой гомопиперазин-1-ильную группу; замещенную в положении 3 амино-, алкиламино-, диалкиламино-, алкидкарбониламино- или алкоксикарбониламиногруппой 8-азабицикло[3.2.1]окт-8-ильную группу; или группу (R4NR5), в которой: R4 означает атом водорода или алкильную группу и R5 означает атом водорода, замещенную циклоалкильной группой с 5-6 атомами углерода метильную группу, в которой циклоалкильная часть в положении 3 или 4 замещена аминогруппой, аминометильной группой, алкиламинометильной группой или диалкиламинометильной группой или одна метиленовая группа в циклоалкильной части заменена атомом кислорода, имино-, N-алкилимино-, N-алкилкарбонилимино-, N-алкоксикарбонилимино-, (пирролидин-1-ил)карбонилимино- или морфолинокарбонилиминогруппой; циклогексилметильную группу, замещенную в положении 3 или 4 циклогексильной части алкоксикарбониламиногруппой или бензилоксикарбониламиногруппой; хинуклидин-4-илметильную группу; этильную группу, замещенную карбоксильной, алкоксикарбонильной, аминокарбонильной, алкиламинокарбонильной, диалкиламинокарбонильной, (пирролидин-1-ил)карбонильной или морфолинокарбонильной группой; этильную группу, которая в положении 2 замещена гидроксильной группой, аминогруппой, цианогруппой или 4-аминоциклогексильной группой; пиперидин-4-ильной группой, которая в положении 1 может быть замещена алкильной, алкилкарбонильной или алкоксикарбонильной группой; циклопентильной группой, в которой одна метиленовая группа заменена имино- или N-алкилиминогруппой; пиперазин-1-ильной группой, которая в положении 4 может быть замещена алкильной, алкоксикарбонильной, алкилкарбонильной, пирролидин-1-илкарбонильной или морфолинокарбонильной группой, 3-оксопиперазин-1-ильной группой, которая в положении 4 может быть замещена алкильной группой; или L 2-оксоимидазолидин-1-ильной группой, которая в положении 3 может быть замещена алкильной группой; 2,2-диалкоксиэтильную группу; алкильную группу с 3-5 атомами углерода, замещенную аминогруппой, при условии, что оба атома азота остатка Rc разделены по меньшей мере двумя атомами углерода; алкильную группу, замещенную пиперазин-1-илкарбонильной группой, которая в положении 4 может быть замещена алкильной, алкоксикарбонильной или алкилкарбонильной группой; алкильную группу с 3-4 атомами углерода, замещенную 4-аминофенильной группой, феноксигруппой, алкилениминогруппой с 5-6 атомами углерода, алкиламиногруппой, диалкиламиногруппой, морфолиногруппой, алкилкарбониламиногруппой, алкилсульфониламиногруппой, алкоксикарбониламиногруппой, пирролидин-1-илкарбониламиногруппой или морфолинокарбониламиногруппой, при условии, что оба атома азота остатка Rc разделены по меньшей мере двумя атомами углерода; фенильную группу, которая в положении 4 замещена алкилкарбониламиногруппой, группой (R8NR7-CO- или (R8NR7)-CO-NR6, причем R6, R7 и R8 могут быть одинаковыми или разными и каждый означает атом водорода или алкильную группу; циклогексильную группу, которая в положении 4 замещена гидроксильной группой, амино-, алкиламино-, диалкиламино-, алкоксикарбониламино-, алкилкарбониламино- или N-(алкил)-N-алкилкарбониламиногруппой; группой (R8NR7)-CO-NR6, причем R6, R7 и R8 имеют вышеуказанные значения, бензоиламино-, фенилсульфониламино-, фенилацетиламино- или 2-фенилпропиониламиногруппой; 5-6-членной алкилениминогруппой, причем в вышеупомянутых пиперидин-1-ильных группах метиленовая группа в положении 4 может быть заменена атомом кислорода, имино-, N-алкилимино-, N-алкилкарбонилимино-, N-алкоксикарбонилимино- или N-алкилсульфонилиминогруппой; или 3-оксопиперазин-1-ильной группой, которая в положении 4 может быть замещена алкильной группой, циано-, карбоксильной, алкоксикарбонильной группой или возможно замещенной одной или двумя алкильными группами с 1-2 атомами углерода (алкиленимино)карбонильной группой, соответственно, с 5-6 атомами в цикле алкилениминочасти, причем в вышеупомянутых пиперидин-1-ильных группах метиленовая группа в положении 4 может быть заменена атомом кислорода или серы, сульфинильной группой, сульфонильной группой, имино-, N-алкилимино-, N-алкилкарбонилимино-, N-алкоксикарбонилимино- или N-алкилсульфонилиминогруппой, (алкиленимино)алкильной группой с 1-2 атомами углерода в алкильнюй части и, соответственно, 5-6 атомами в цикле алкилениминочасти, причем в вышеупомянутых пиперидин-1-ильных группах метиленовая группа в положении 4 может быть заменена атомом кислорода, имино- или N-алкилиминогруппой, алкильной группой с 1-2 атомами углерода, которая замещена амино-, алкиламино-, диалкиламиногруппой, пирролидин-1-илкарбонильной, пиперидин-1-илкарбонильной или морфолинокарбонильной группой; циклогексильную группу, которая в положении 3 замещена амино-, алкиламино- или диалкиламиногруппой; циклогексильную группу, в которой метиленовая группа в положении 3 или 4 заменена имино- или N-алкилиминогруппой или метиленовая группа в положении 4 заменена атомом кислорода или серы, сульфинильной группой, сульфонильной группой, N-формилимино-, N-цианимино-, N-алкилкарбонилимино-, N-алкоксикарбонилимино-, N-(2-аминоэтил)имино-, N-аминокарбонилимино-, N-алкиламинокарбонилимино-, N-(диалкиламинокарбонил)имино-, Н-(морфолинокарбонил)-имино- или N-(пирролидин-1-илкарбонил)иминогруппой; 4-оксоциклогексильную группу; циклопентильную группу, которая в положении 3 замещена аминогруппой, алкиламиногруппой, диалкиламиногруппой, карбоксильной, алкоксикарбонильной, аминокарбонильной, алкиламинокарбонильной, диалкиламинокарбонильной, морфолинокарбонильной или пирролидин-1-илкарбонильной группой или в положении 1 также замещена гидроксиалкильной группой с 1-2 атомами углерода; пирролидин-3-ильную группу, которая в положении 1 замещена (алкиленимино)кар6онильной группой, соответственно, с 5-6 атомами в цикле алкилениминочасти, причем в вышеупомянутых пиперидин-1-ильных группах метиленовая группа в положении 4 может быть заменена атомом кислорода или имино-, N-алкилимино-, N-алкоксикарбонилимино- или N-алкилкарбонилиминогруппой; бензильную группу, замещенную в положении 4 амино-, алкиламино- или диалкиламиногруппой; циклогептильную группу, в которой метиленовая группа в положении 4 заменена имино-, N-бензилимино-, N-алкилимино-, N-алкилкарбонилимино-, N-алкоксикарбонилимино- или N-алкилсульфонилиминогруппой, или хинуклидин-3-ильную группу; причем, если не указано ничего другого, упомянутые выше алкильные, алкиленовые и алкоксильные части содержат, соответственно, 1-4 атома углерода, при условии, что (i) группа RaNRb не является (3-хлор-4-фторфенил)аминогруппой, если Rc одновременно означает замещенную в положении 4 амино- или диметиламиногруппой пиперидин-1-ильную группу; 1-метилпиперидин-1-илоксигруппу, транс-4-гидроксициклогексиламино-, морфолино-, N-(4-гидроксициклогексил)-N-метиламино- или тетрагидрофурфуриламиногруппу; (ii) группа RaNRb не является (3-метилфенил)аминогруппой, если Rc одновременно означает пиперидин-1-ильную группу, незамещенную или замещенную в положении 3 или 4 гидроксильной группой или в положении 4 аминокарбонильной группой, амино-, ацетиламино-, метоксикарбониламино- или формиламиногруппой, аминогруппу, алкиламиногруппу с 1-4 атомами углерода, цис-2,5-диметилморфолино-, хинуклидин-3-иламино-, 2-гидроксиэтиламино-, тетрагидропиран-4-иламино-, N-4-гидроксициклогексил)-N-метиламино-, 4-оксоциклогексиламино- или цис-4-гидроксициклогексиламиногруппу; пиперидин-4-иламиногруппу, незамещенную или замещенную в положении 1 метильной, ацетильной, метоксикарбонильной или этоксикарбонильной группой; циклогексиламиногруппу, замещенную в положении 4 в трансконфигурации карбоксильной, метоксикарбонильной, (пирролидин-1-ил)кар6онильной, морфолинокарбонильной группой, амино-, диметиламино-, ацетиламино-, 4-трет.-бутилоксикарбониламиногруппой или гидроксильной группой; (iii) группа RaNRb не является фениламино-, (3-метилфенил)амино-, (3-бромфенил)амино-, (3-хлорфенил)амино- или (3-фторфенил)аминогруппой, если Rc одновременно означает морфолиногруппу; (iv) группа RaNRb, не является (3-фторфенил)амино-, (3-хлорфенил)амино- или (3-бромфенил)аминогруппой, если Rc одновременно означает изопропиламиногруппу; или (v) группа RaNRb не является (3-фторфенил)амино-, (3-хлор-4-метоксифенил)-амино-, (4-хлор-3-нитрофенил)амино-, (4-амино-3-нитрофенил)амино-, (4-амино-3,5-дихлорфенил)амино-, (4-амино-3-цианофенил)амино-, (4-амино-3,5-дибромфенил)амино-, (3,4-дихлорфенил)амино-, (3-хлорфенил)амино- или (3-бромфенил)аминогруппой, если Rc одновременно означает транс-4-гядроксициклогексиламиногруппу;
их таутомеры, стереоизомеры и соли.1. Pyrimido [5,4-d] pyrimidines of the general formula (I)
where R a means a hydrogen atom; R b means a phenyl group substituted by residues from R 1 to R 3 , which may be the same or different, and R 1 means a hydrogen, fluorine, chlorine or bromine atom, trifluoromethoxy group, methyl, hydroxymethyl, trifluoromethyl, ethynyl group, nitro, cyano -, phenoxy group, phenyl group, benzyloxy group, benzyl group, 1,1,2,2-tetrafluoroethoxy or methoxy group, R 2 means a hydrogen atom, amino, methylamino or dimethylamino group and R 3 means a hydrogen, fluorine, chlorine or bromine atom ; or R a and R b together with the nitrogen atom between them mean an indolin-1-yl or 1,2,3,4-tetrahydroquinolin-1-yl group; and R c is a cyclopentyloxy group in which the methylene group at position 3 is replaced by an oxygen atom or an N-alkylimino group; a cyclohexyloxy group in which the methylene group at position 4 is replaced by an oxygen atom or an N-alkylimino group; a pyrrolidin-1-yl group which at position 3 is substituted with an amino, alkylamino, dialkylamino group or a 4-hydroxyphenyl group and optionally an additional methyl group; piperidin-1-yl group which may be substituted by aminomethyl, alkylaminomethyl, dialkylaminomethyl, (pyrrolidin-1-yl) methyl, (piperidin-1-yl) methyl, (piperazin-1-yl) methyl, (4-methylpiperazin-1 -yl) methyl, morpholinomethyl, alkylcarbonylaminomethyl, alkylsulphonylaminomethyl, cyanomethyl, aminocarbonylmethyl, aminocarbonyl, (piperazin-1-yl) car6onyl, (4-methylpiperazin-1-yl) carbonyl, 2-carboxyethyl-2-carboxyethyl-2-carboxyethyl-2-carboxyethyl -ethyl, 2-aminoethyl, 2-aminocarbonyl threshing, alkilaminokarboniletilnoy-2, 2-dialkilaminokarboniletilnoy, 2- (pyrrolidin-1-ilkar6onil) ethyl group, karboksimetiloksigruppoy, alkoksikarbonilmetiloksigruppoy, aminokarbonilmetiloksigruppoy, alkilaminokarbonilmetiloksigruppoy, dialkilaminokarbonilmetiloksigruppoy, morfolinokarbonilmetiloksigruppoy (pyrrolidin-1-yl) karbonilmetiloksigruppoy, piperidin-4-yl or 1 a methylpiperidin-4-yl group; a piperidinyl-1-yl group which is substituted at the 3 or 4 position by an amino group and is optionally further substituted by one or two methyl groups or a hydroxyl, alkoxy group, formylamino, alkylamino, dialkylamino, morpholinocarbonylamino, alkoxycarbonylamino, alkylcarbonylamino, morpholinogroup, pyrrolidin-1-yl, piperidin-1-yl, piperazin-1-yl, 4-methylpiperazin-1-yl, 4-dimethylaminopiperidin-1-yl, 4-aminopiperidin-1-yl, 2-oxopyrrolidin-1-yl, 4-hydroxypiperidin-1-yl, 4-methylaminopiperidin-1-yl oh, 3-oxopiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl group, N-acetyl-N-methylamino, N-methyl-N-methylsulfonylamino, 2-oxoimidazolidin-1-yl or 3- methyl-2-oxoimidazolidin-1-yl group; A 1-azacycloheptyl group unsubstituted or substituted at position 3 or 4 by an amino group, a hydroxyl group, an alkoxy group, an alkylamino group, a dialkylamino group, an alkoxycarbonylamino group or an alkylcarbonylamino group; unsubstituted or substituted by one or two grave groups morpholino group; a piperazin-1-yl group which at position 4 is substituted with a 2-aminoethyl, 2-alkylaminoethyl, 2-dialkylaminoethyl, morpholinocarbonyl or alkoxy substituted phenyl group; an unsubstituted or substituted at position 4 alkyl group of a homopiperazin-1-yl group; the 8-azabicyclo [3.2.1] oct-8-octyl group substituted at the 3-position by an amino, alkylamino, dialkylamino, alkydcarbonylamino or alkoxycarbonylamino group; or a group (R 4 NR 5 ) in which: R 4 means a hydrogen atom or an alkyl group and R 5 means a hydrogen atom substituted by a cycloalkyl group with 5-6 carbon atoms, a methyl group in which the cycloalkyl part in position 3 or 4 is substituted by an amino group , an aminomethyl group, an alkylaminomethyl group or a dialkylaminomethyl group, or one methylene group in the cycloalkyl part is replaced by an oxygen atom, imino, N-alkylimino, N-alkylcarbonylimino, N-alkoxycarbonylimino, (pyrrolidin-1-yl) carbonylimino or morpholinocarbonylimino group; a cyclohexylmethyl group substituted at the 3 or 4 position of the cyclohexyl moiety with an alkoxycarbonylamino group or a benzyloxycarbonylamino group; quinuclidin-4-ylmethyl group; an ethyl group substituted with a carboxyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, (pyrrolidin-1-yl) carbonyl or morpholinocarbonyl group; an ethyl group which at position 2 is substituted with a hydroxyl group, an amino group, a cyano group or a 4-aminocyclohexyl group; a piperidin-4-yl group which at position 1 may be substituted with an alkyl, alkylcarbonyl or alkoxycarbonyl group; a cyclopentyl group in which one methylene group is replaced by an imino or N-alkylimino group; a piperazin-1-yl group which at position 4 may be substituted by an alkyl, alkoxycarbonyl, alkylcarbonyl, pyrrolidin-1-ylcarbonyl or morpholinocarbonyl group, a 3-oxopiperazin-1-yl group which at position 4 may be substituted by an alkyl group; or an L 2-oxoimidazolidin-1-yl group, which at position 3 may be substituted with an alkyl group; 2,2-dialkoxyethyl group; an alkyl group with 3-5 carbon atoms substituted by an amino group, provided that both nitrogen atoms of the residue R c are separated by at least two carbon atoms; an alkyl group substituted by a piperazin-1-ylcarbonyl group which at position 4 may be substituted by an alkyl, alkoxycarbonyl or alkylcarbonyl group; alkyl group with 3-4 carbon atoms, a substituted 4-aminophenyl group, a phenoxy group, alkileniminogruppoy with 5-6 carbon atoms, alkylamino, dialkylamino, morpholino, alkylcarbonylamino, alkylsulfonylamino, alkoxycarbonylamino, pyrrolidin-1-ilkarbonilaminogruppoy or morfolinokarbonilaminogruppoy, provided that both the nitrogen atoms of the residue R c are separated by at least two carbon atoms; a phenyl group which at position 4 is substituted with an alkylcarbonylamino group, a group (R 8 NR 7 —CO— or (R 8 NR 7 ) —CO — NR 6 , wherein R 6 , R 7 and R 8 may be the same or different and each represents an atom hydrogen or an alkyl group; a cyclohexyl group which at position 4 is substituted with a hydroxyl group, amino, alkylamino, dialkylamino, alkoxycarbonylamino, alkylcarbonylamino or N- (alkyl) -N-alkylcarbonylamino; group (R 8 NR 7 ) -CO -NR 6 , with R 6 , R 7 and R 8 having the above meanings, benzoylamino, phenylsulfonylamino, phenylacetylamino or 2-pheni lpropionylamino group; a 5-6-membered alkyleneimino group, wherein in the above piperidin-1-yl groups, the methylene group at position 4 can be replaced by an oxygen atom, imino, N-alkylimino, N-alkylcarbonylimino, N-alkoxycarbonylimino or N-alkylsulfonylimino ; or a 3-oxopiperazin-1-yl group, which at position 4 may be substituted by an alkyl group, a cyano, carboxyl, alkoxycarbonyl group or optionally substituted by one or two alkyl groups with 1-2 carbon atoms (alkyleneimino) carbonyl groups correspondingly, with 5-6 atoms in the alkylene-amino group cycle, and in the above piperidin-1-yl groups, the methylene group in position 4 can be replaced by an oxygen or sulfur atom, a sulfinyl group, a sulfonyl group, imino, N-alkylimino, N -alkylcarbonylimino-, N-alkoxycarbonylimino- or N-alkylsulfonylimino group, (alkylenimino) alkyl group with 1-2 carbon atoms in the alkyl part and, correspondingly, 5-6 atoms in the alkylene-amino group cycle, and in the above piperidin-1-yl groups the methylene group in position line 4 can be replaced by an oxygen atom, an imino- or N-alkylimino group, an alkyl group with 1-2 carbon atoms, which is substituted by an amino, alkylamino, dialkylamino group, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl or morpholinocarbonyl group; a cyclohexyl group which at position 3 is substituted with an amino, alkylamino or dialkylamino group; cyclohexyl group in which the methylene group at position 3 or 4 is replaced by an imino or N-alkylimino group or the methylene group at position 4 is replaced by an oxygen or sulfur atom, a sulfinyl group, a sulfonyl group, N-formylimino, N-cyanimino, N-alkylcarbonylimino -, N-alkoxycarbonylimino, N- (2-aminoethyl) imino, N-aminocarbonylimino, N-alkylaminocarbonylimino, N- (dialkylaminocarbonyl) imino, N- (morpholinocarbonyl) imino or N- (pyrrolidin-1 -alkylcarbonyl) imino group; 4-oxocyclohexyl group; a cyclopentyl group which at position 3 is substituted by an amino group, an alkylamino group, a dialkylamino group, a carboxyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, morpholinocarbonyl or pyrrolidin-1-ylcarbonyl group or at position 1 is also substituted by a hydroxyalkyl group; a pyrrolidin-3-yl group which is substituted at the 1-position with an (alkylenimino) car6onyl group, respectively, with 5-6 atoms in the alkylene-amino cycle, and in the above piperidin-1-yl groups, the methylene group at the 4-position can be replaced by an oxygen or imino atom -, N-alkylimino-, N-alkoxycarbonylimino- or N-alkylcarbonylimino; a benzyl group substituted at position 4 with an amino, alkylamino or dialkylamino group; a cycloheptyl group in which the methylene group at position 4 is replaced by an imino, N-benzylimino, N-alkylimino, N-alkylcarbonylimino, N-alkoxycarbonylimino or N-alkylsulfonylimino group, or a quinuclidin-3-yl group; moreover, if nothing else is indicated, the above-mentioned alkyl, alkylene and alkoxyl parts contain, respectively, 1-4 carbon atoms, provided that (i) the group R a NR b is not a (3-chloro-4-fluorophenyl) amino group if R c simultaneously means a piperidin-1-yl group substituted at the 4-position with an amino or dimethylamino group; 1-methylpiperidin-1-yloxy group, trans-4-hydroxycyclohexylamino, morpholino-, N- (4-hydroxycyclohexyl) -N-methylamino or tetrahydrofurfurylamino group; (ii) the group R a NR b is not a (3-methylphenyl) amino group if R c simultaneously means a piperidin-1-yl group unsubstituted or substituted at position 3 or 4 with a hydroxyl group or at position 4 with an aminocarbonyl group, amino, acetylamino -, methoxycarbonylamino or formylamino group, amino group, alkylamino group with 1-4 carbon atoms, cis-2,5-dimethylmorpholino-, quinuclidin-3-ylamino-, 2-hydroxyethylamino, tetrahydropyran-4-ylamino-, N-4-hydroxycyclohexyl ) -N-methylamino, 4-oxocyclohexylamino or cis-4-hydroxycyclohexylamino; piperidin-4-ylamino group unsubstituted or substituted at position 1 by a methyl, acetyl, methoxycarbonyl or ethoxycarbonyl group; a cyclohexylamino group substituted at position 4 in the trans configuration of a carboxyl, methoxycarbonyl, (pyrrolidin-1-yl) car6onyl, morpholinocarbonyl group, amino, dimethylamino, acetylamino, 4-tert-butyloxycarbonylamino group or hydroxyl group; (iii) the group R a NR b is not phenylamino, (3-methylphenyl) amino, (3-bromophenyl) amino, (3-chlorophenyl) amino, or (3-fluorophenyl) amino, if R c simultaneously means a morpholino group ; (iv) a group R a NR b , is not a (3-fluorophenyl) amino, (3-chlorophenyl) amino or (3-bromophenyl) amino group, if R c simultaneously means an isopropylamino group; or (v) the group R a NR b is not (3-fluorophenyl) amino, (3-chloro-4-methoxyphenyl) amino, (4-chloro-3-nitrophenyl) amino, (4-amino-3 nitrophenyl) amino, (4-amino-3,5-dichlorophenyl) amino, (4-amino-3-cyanophenyl) amino, (4-amino-3,5-dibromophenyl) amino, (3,4 a dichlorophenyl) amino, (3-chlorophenyl) amino or (3-bromophenyl) amino group, if R c simultaneously means a trans-4-hydroxycyclohexylamino group;
their tautomers, stereoisomers and salts.
их таутомеры, стереоизомеры и соли.2. Pyrimido [5,4-d] pyrimidines of the general formula (I) according to claim 1, provided that (i) the group R a NR b is not a (3-chloro-4-fluorophenyl) amino group if R c is simultaneously means a piperidin-1-yl group substituted at position 3 with an amino, dimethylamino, acetylamino or methoxycarbonylamino group or at position 4 with an amino or dimethylamino group; an unsubstituted or substituted at position 1 methyl group with a piperidin-3-ylamino group; a pyrrolidin-1-yl group substituted at the 3-position with an amino or dimethylamino group; a piperazin-1-yl group substituted at the 4-position with a 2-aminoethyl group; a cyclohexylamino group substituted at position 4 with a carboxyl, (pyrrolidin-1-yl) carbonyl, morpholinocarbonyl, 2- (morpholinocarbonyl) ethyl group, amino, dimethylamino, acetylamino group, hydroxyl group, N-acetyl-N-methylamino group, pyrrolidin-1- a yl group or morpholino group; An N- (4-hydroxycyclohexyl) -N-methylamino group; a methoxycarbonylamino or morpholino group substituted at position 3 with an n-propylamino group; A 2- (piperazin-1-yl) ethylamino group unsubstituted or substituted at the 4-position of the piperazinyl moiety by a methyl, acetyl or methoxycarbonyl group; 1-hydroxymethylcyclopentylamino, N- (2-hydroxyethyl) -N-ethylamino, 2- (acetylamino) ethylamino, tetrahydrofurfurylamino, tetrahydropyran-4-ylamino, 4-oxocyclohexylamino, morpholino-, piperidin-4-ylamino , 1-methylpiperidin-4-ylamino, tert.-butylamino, isopropylamino, tetrahydrofuran-3-yloxy, tetrahydropyran-4-yloxy, 1-methylpiperidin-4-yloxy or 1-methylpyrrolidin-3-yloxy; (ii) the group R a NR b is not a (3-methylphenyl) amino group if R c simultaneously means a piperidin-1-yl group unsubstituted or substituted at position 3 or 4 with a hydroxyl group or at position 4 with an aminocarbonyl group, amino, acetylamino -, methoxycarbonylamino or formylamino; a cyclohexylamino group substituted at position 4 with a carboxyl, methoxycarbonyl, (pyrrolidin-1-yl) carbonyl, morpholinocarbonyl group, amino, dimethylamino, acetylamino, tert-butyloxycarbonylamino group or hydroxyl group; piperidin-4-ylamino group unsubstituted or substituted at position 1 by methyl, acetyl, methoxycarbonyl, N-methylaminocarbonyl, N, N-dimethylaminocarbonyl, formyl group, cyano group, aminocarbonyl or ethoxycarbonyl group; an amino group, an alkylamino group with 1-4 carbon atoms, 2-hydroxyethylamino, 4-oxocyclohexylamino, N- (4-hydroxycyclohexyl) -N-methylamino, tetrahydrofurfurylamino, tetrahydropyran-4-ylamino, 3-methylmorpholino- or quinuclidine- 3-ylamino group; 3,3-, 3,5-, cis-2,5- or trans-2,5-dimethylmorpholine group; (iii) the group R a NR b is not phenylamino, (3-methylphenyl) amino, (3-bromophenyl) amino, (3-chlorophenyl) amino, (3-fluorophenyl) amino, (4-amino 3-nitrophenyl) amino, (3,4-dichlorophenyl) amino, (3-nitrophenyl) amino, or (3-ethynylphenyl) amino group, if R c simultaneously means a morpholino group; (iv) the group R a NR b is not a (3,4-dichlorophenyl) amino, (3-chlorophenyl) amino, (3-bromophenyl) amino, (3-nitrophenyl) amino or (3-ethynylphenyl) amino if R c simultaneously means a cyclohexylamino group substituted at position 4 with a carboxyl, (pyrrolidin-1-yl) carbonyl, morpholinocarbonyl group, amino, dimethylamino, acetylamino group or hydroxyl group; tert-butylamino, isopropylamino, N- (4-hydroxycyclohexyl) -N-methyl-amino, tetrahydropyran-4-ylamino, tetrahydrofurfurylamino, 4-oxocyclohexylamino, piperidin-4-ylamino or 1-methylpiperidine 4-ylamino group; (v) the group R a NR b is not a (3-fluorophenyl) amino group, if R c simultaneously means an isopropylamino group; or (vi) the group R a NR b is not (3-fluorophenyl) amino, (3-chloro-4-methoxyphenyl) amino, (4-chloro-3-nitrophenyl) amino, (4-amino-3 -nitrophenyl) amino-, (4-amino-3,5-dichlorophenyl) amino, (4-amino-3-cyanophenyl) amino, (4-amino-3,5-di6romophenyl) amino, (4-amino -3-chloro-5-bromophenyl) amino or (3,5-dichloro-4-dimethylaminophenyl) amino group, if R c simultaneously means 4-hydroxycyclohexylamino group;
their tautomers, stereoisomers and salts.
за исключением следующих соединений: 4-[(4-амино-3,5-дибромфенил)амино] -6-[(транс-4-гидроксициклогексил)амино] -пиримидо[5,4] пиримидин; 4-[(3-хлор-4-фторфенил)амино] -6-[4-аминoпипepидин-1-ил]пиpимидo[5,4-d]-пиримидин; 4-[(3-хлор-4-фторфенил)амино] -6-[3-аминопирролидин-1-ил] пиримидо[5,4-d] -пиримидин; 4-[(3-хлор-4-фторфенил)амино]-6-[4-(2-аминоэтил)пиперазин-1-ил] пиримидо-[5,4-d] пиримидин; 4-[(3-хлор-4-фторфенил)амино]-6-[3-аминопиперидин-1-ил] пиримидо[5,4-d] -пиримидин; 4-[(3-хлор-4-фторфенил)амино] -6-[пиперидин-3-иламино]пиримидо[5,4-d]пиримидин; 4-[(3-хлор-4-фторфенил)амино] -6-[1-метилпиперидин-3-иламино] пиримидо-[5,4-d] пиримидин; 4-[(3-хлор-4-фторфенил)амино] -6-[4-(N-ацетил-N-метиламино)циклогексил-амино] пиримидо[5,4-d] пиримидин; 4-[(3-хлор-4-фторфенил)амино] -6-[4-(пирролидин-1-ил)циклогексиламино] пиимидо[5,4-d] пиримидин; 4-[(3-хлор-4-фторфенил)амино] -6-[4-(морфолино)циклогексиламино] пиримидо[5,4-d] пиримидин; 4-[(3-хлор-4-фторфенил)амино] -6-[транс-4-(2-(морфолинокарбонил)этил)циклогексиламино] пиримидо[5,4-d] пиримидин; 4-[(4-амино-3-нитрофенил)амино]-6-[(транс-4-гидроксициклогексил)амино] пиримидо[5,4-d] пиримидин; 4-[(4-хлор-3-нитрофенил)амино] -6-[(транс-4-гидроксициклогексил)амино] пиримидо[5,4-d]пиримидин; 4-[(4-амино-3,5-дихлорфенил)амино] -6-[(транс-4-гидроксициклогексил)амино] пиримидо[5,4-d]пиримидин; 4-[(3-хлор-4-фторфенил)амино]-6-[1-(гидроксиметил)циклопентиламино] пиримидо[5,4-d)пиримидин; 4-[(3-хлор-4-фторфенил)амино]-6-[N-метил-N-(2-гидроксиэтил)амино]пиримидо[5,4-d)пиримидин; 4-[(3-хлор-4-фторфенил)амино]-6-[3-(метоксикарбониламино)проп-1-иламино] пиримидо[5,4-d]пиримидин; ^ 4-[(3-хлор-4-фторфенил)амино] -6-[3-(морфолино)проп-1-иламино] пиримидо[5,4-d]пиримидин; 4-[(3-хлор-4-фторфенил)амино]-6-[2-(пиперазин-1-ил)-1-этиламино]пиримидо[5,4-d] пиpимидин; 4-[(3-хлор-4-фторфенил)амино]-6-[2-(1-ацетилпиперазин-4-ил)этиламино] пиримидо[5,4-d)пиримидин; 4-[(4-амино-3-нитрофенил)амино]-6-(морфолино)пиримидо[5,4-d] пиримидин; 4-[(3-хлор-4-фторфенил)амино] -6-(тетрагидропиран-4-илокси)пиримидо[5,4-d] пиримидин; 4-[(3-хлор-4-фторфенил)амино]-6-(тетрагидрофуран-3-илокси)пиримидо[5,4-d]пиримидин;
а также соединений, в которых группа RaNRb означает 3-хлорфениламино-, (3-хлор-4-фторфенил)амино-, (3-нитрофенил)амино- или (3-этинилфенил)аминогруппу, если Rc одновременно означает тетрагидропиран-4-иламино-, тетрагидрофурфуриламино-, 4-оксоциклогексиламино-, циклогексиламино-, морфолино-, пиперидин-4-иламино-, изопропиламино-, 1-метилпиперидин-4-иламино-, трет. -бутиламино-, N-(4-гидроксициклогексил)-N-метиламино-, 4-гидроксициклогексиламино-, 4-аминоциклогексиламино-, 4-диметиламиноциклогексиламино-, транс-4-карбоксициклогексиламино-, транс-4-(пирролидин-1-ил)карбонилциклогексиламино- или транс-4-морфолинокарбонилциклогексиламиногруппу;
их таугомеры, стереоизомеры и соли.3. Pyrimido [5,4-d] pyrimidines of the general formula (I) according to claim 1, wherein R a is a hydrogen atom; R b means 3-chlorophenyl, 3-chloro-4-fluorophenyl, 3- (1,1,2,2-tetrafluoroethoxy) phenyl, 4-amino-3,5-dibromophenyl, 4-amino-3,5-dichlorophenyl, 4- (benzyloxy) phenyl, 3- (benzyloxy) phenyl, 4- (benzyloxy) phenyl, 4- (benzyloxy) -3-chlorophenyl, 3- (hydroxymethyl) phenyl, biphenyl-4-yl, 3-phenoxyphenyl, 4- phenoxyphenyl, 3-chloro-4-phenoxyphenyl, 3-cyanophenyl, 3-trifluoromethoxyphenyl, 3-trifluoromethylphenyl, 3,4-difluorophenyl, 3-nitrophenyl, 3-ethynylphenyl, 4-amino-3-nitrophenyl, 4-chloro-3- nitrophenyl, 3-chloro-4-cyanophenyl or 4- chloro-3-cyanophenyl group; or R a and R b together with the nitrogen atom between them mean an indolin-1-yl or 1,2,3,4-tetrahydroquinolin-1-yl group; and R c is tetrahydrofuran-3-yloxy or tetrahydropyran-4-yloxy; a pyrrolidin-1-yl group substituted at the 3-position with an amino, methylamino or ethylamino group; substituted at position 4 with a 4-hydroxyphenyl group and optionally at position 2 with a methyl group, a pyrrolidin-1-yl group; a piperidin-1-yl group substituted at position 2 with an aminomethyl, (pyrrolidin-1-yl) methyl or dimethylaminomethyl group; a piperidin-1-yl group substituted at position 3 by an amino group, an aminomethyl, aminocarbonyl, aminocarbonylmethyl, acetylaminomethyl or methylsulfonylaminomethyl group; a piperidin-1-yl group unsubstituted or substituted at position 4 by an amino group, a hydroxyl group, formylamino, methoxy, methylamino, ethylamino, morpholinocarbonylamino, methoxycarbonylamino, acetylamino, aminomethyl, methylaminomethyl, ethylaminomethyl, 2-carboxyethyl methoxycarbonylethyl, 2- (morpholinocarbonyl) ethyl, 2-aminoethyl, 2-aminocarbonylethyl, 2-methylaminocarbonylethyl, 2-dimethylaminocarbonylethyl, 2- (pyrrolidinocarbonyl) ethyl group, carboxymethyloxy, methoxycarbonylmethyl loxy-, aminocarbonylmethyloxy-, methylaminocarbonylmethyloxy-, dimethylaminocarbonylmethyloxy-, morpholinocarbonylmethyloxy-, (pyrrolidin-1-yl) -carbonylmethyloxy-, morpholino-group, pyrrolidin-1-yl, piperidin-1-piperidyl-1-piperidinyl-1-piperidinyl-1-piperidinyl-1-piperidinyl 4-yl, piperazin-1-yl, 4-methylpiperazin-1-yl, 4-dimethylaminopiperidin-piperidin-1-yl, 4-aminopiperidin-1-yl, 2-hydroxypyrrolidin-1-yl, 4-hydroxypiperidin-1- a 4-methylaminopiperidin-1-yl, 3-oxo-piperazin-1-yl, 4-methyl-3-oxo-piperazin-1-yl group, N-acetyl-N-methyl amino, N-methyl-N-methylsulfonylamino, (piperidin-1-yl) methyl, (piperazin-1-yl) methyl, (4-methylpiperazin-1-yl) methyl, morpholinomethyl, (pyrrolidin-1-yl) methyl , dimethylaminomethyl, acetylaminomethyl, methylsulfonylaminomethyl, cyanomethyl, (piperazin-1-yl) -carbonyl, (4-methylpiperazin-1-yl) car6onyl, 2-oxoimidazolidin-1-yl or 3-methyl-2-oxo-imidazole ; a piperidin-1-yl group substituted with a methyl group and optionally at position 4 with an amino group; A 1-azacycloheptyl or 4-amino-1-azacycloheptyl group; morpholino or 2,6-dimethylmorpholinogroup; a piperazin-1-yl group substituted at the 4-position with a 2-aminoethyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl or morpholinocarbonyl group; homopiperazin-1-yl or 4-methyl homopiperazin-1-yl group; An 8-aza-6-cyclo [3.2.1] oct-8-yl group substituted at the 3-position by an amino, methylamino, dimethylamino or acetylamino group, or a group (R 4 NR 5 ) in which: R 4 represents a hydrogen atom, methyl or ethyl group; R 5 means a hydrogen atom, an isopropyl or tert.-butyl group; methyl group substituted with piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, 1-methylpiperidin-4-yl, 1-tert-butyloxycarbonylpiperidin-4-yl, 1-acetylpiperidin-4-yl, 1 - (morpholinocarbonyl) piperidin-4-yl, 1-ethylpyrrolidin-2-yl, 1-ethylpyrrolidin-3-yl, 3-aminomethylcyclopentyl, tetrahydrofur-3-yl, quinuclidin-4-yl, piperazin-1-yl-carbonyl 4 methylpiperazin-1-ylcarbonyl or 4-acetylpiperazin-1-ylcarbonyl group; an ethyl group substituted at position 1 with a carboxyl, methoxycarbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, pyrrolidin-1-ylcarbonyl, morpholinocarbonyl, piperazin-1-ylcarbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-acetyl at position 2 with a hydroxyl group, an amino group, a cyano group, piperidin-4-yl, 1-acetylpiperidin-4-yl, 1-methoxycarbonylpiperidin-4-yl, 1-methylpyrrolidin-2-yl, piperazin-1-yl, 3-oxopiperazin- 1-yl, 4-methyl-3-oxopy perazin-1-yl, 4-tert. -butyloxycarbonylpiperazin-1-yl, 4-acetylpiperazin-1-yl, 4- (morpholinocarbonyl) piperazin-1-yl, 2-oxoimidazolidin-1-yl, 3-methyl-2-oxoimidazolidin-1-yl or 4-aminocycle ; 2,2-dimethoxyethyl group; a prop-1-yl group which at position 2 is substituted with an amino group and can additionally be substituted at position 2 with a methyl group; a prop-1-yl group which at position 3 is substituted with an amino, morpholino, acetylamino, methylsulfonylamino, methoxycarbonylamino or morpholinocarbonylamino group; a prop-2-yl group which at position 1 is substituted with an amino group, phenoxy group, 4-aminophenyl, piperidin-1-yl or diethylamino group; a prop-2-yl group which is substituted at position 1 by an amino group and additionally at position 2 by a methyl group; a prop-2-yl group which at position 2 is substituted with a (piperazin-1-yl) carbonyl, (4-methylpiperazin-1-yl) -carbonyl or (4-acetylpiperazin-1-yl) carbonyl group; A 4-aminobutyl or 5-aminopentyl group, a phenyl group which at position 4 is substituted with acetylamino, dimethylaminocarbonyl, dimethylaminocarbonidamino, ethylaminocarbonylamino or N- (dimethylaminocarbonyl) -N-methylamino; the cyclohexyl group which at position 4 is substituted with a hydroxyl group, amino, methylamino, ethylamino, dimethylamino, methoxycarbonylamino, N-acetyl-N-methylamino, dimethylaminocarbonylamino, ethylaminocarbonylamino, benzoylamino, phenylsulfonylamino, phenylacetyl 2-phenylpropionylamino, morpholino, pyrrolidin-1-yl, piperidin-1-yl, 4-aminopiperidin-1-yl, 4-dimethylaminopiperidin-1-yl, piperazin-1-yl, 1-methylpiperazin-4-yl, 3 -oxopiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, 4-acetylpiperazin-1-yl th group, cyano group, carboxyl, morpholinocarbonyl, (pyrrolidin-1-yl) -carbonyl, methoxycarbonyl, (4-methylpiperazin-1-yl) carbonyl, (piperazin-1-yl) carbonyl, (2,6-dimethylmorpholino) carbonyl, thiomorpholinocarbonyl, S-oxidothiomorpholinocarbonyl, S, S-dioxidothiomorpholino carbonyl, (4-acetylpiperazin-1-yl) carbonyl, aminomethyl, methylaminomethyl, ethylaminomethyl, dimethylaminomethyl, piperidin-1-methylmethyl-1-pyrol of ethyl ethyl 4-methylpiper yn-1-ylmethyl, 2-aminoethyl, 2- (morpholinocarbonyl) ethyl or 2- (pyrrolidin-1-ylcarbonyl) ethyl group; 3-aminocyclohexyl or 3-dimethylaminocyclohexyl group; 4-oxocyclohexyl group; a cyclohexylmethyl group which at the cyclohexyl part is substituted at position 4 by an amino group, an aminomethyl group or a benzyloxycarbonylamino group or at position 3 by an aminomethyl group; unsubstituted or substituted at position 1 with a methyl or ethyl group, a piperidin-3-yl group; a piperidin-4-yl group unsubstituted or substituted at position 4 with a formyl group, cyano group, methyl, tert.-butyloxycarbonyl, methoxycarbonyl, 2-aminoethyl, morpholinocarbonyl or (N, N-dimethylamino) carbonyl group; a cyclopentyl group which is substituted at position 1 with a hydroxymethyl group or at position 3 with an amino, carboxyl, methoxycarbonyl or morpholinocarbonyl group; 4-aminobenzyl group; tetrahydropyran-4-yl group, S-oxide-tetrahydrothiopyran-4-yl group or 8,3-dioxidotetrahydrothiopyran-4-yl group; quinuclidin-3-yl, 1-benzyl-4- (azacycloheptyl) -, 1-tert. -butyloxycarbonyl-4- (azacycloheptyl) -, 4- (azacycloheptyl) - or 1- (morpholinocarbonyl) pyrrolidin-3-yl group;
with the exception of the following compounds: 4 - [(4-amino-3,5-dibromophenyl) amino] -6 - [(trans-4-hydroxycyclohexyl) amino] pyrimido [5,4] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4-aminopiperidin-1-yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [3-aminopyrrolidin-1-yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- (2-aminoethyl) piperazin-1-yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [3-aminopiperidin-1-yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [piperidin-3-ylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [1-methylpiperidin-3-ylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- (N-acetyl-N-methylamino) cyclohexyl-amino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- (pyrrolidin-1-yl) cyclohexylamino] pyimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- (morpholino) cyclohexylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [trans-4- (2- (morpholinocarbonyl) ethyl) cyclohexylamino] pyrimido [5,4-d] pyrimidine; 4 - [(4-amino-3-nitrophenyl) amino] -6 - [(trans-4-hydroxycyclohexyl) amino] pyrimido [5,4-d] pyrimidine; 4 - [(4-chloro-3-nitrophenyl) amino] -6 - [(trans-4-hydroxycyclohexyl) amino] pyrimido [5,4-d] pyrimidine; 4 - [(4-amino-3,5-dichlorophenyl) amino] -6 - [(trans-4-hydroxycyclohexyl) amino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [1- (hydroxymethyl) cyclopentylamino] pyrimido [5,4-d) pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [N-methyl-N- (2-hydroxyethyl) amino] pyrimido [5,4-d) pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [3- (methoxycarbonylamino) prop-1-ylamino] pyrimido [5,4-d] pyrimidine; ^ 4 - [(3-chloro-4-fluorophenyl) amino] -6- [3- (morpholino) prop-1-ylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [2- (piperazin-1-yl) -1-ethylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [2- (1-acetylpiperazin-4-yl) ethylamino] pyrimido [5,4-d) pyrimidine; 4 - [(4-amino-3-nitrophenyl) amino] -6- (morpholino) pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- (tetrahydropyran-4-yloxy) pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- (tetrahydrofuran-3-yloxy) pyrimido [5,4-d] pyrimidine;
as well as compounds in which the group R a NR b means 3-chlorophenylamino, (3-chloro-4-fluorophenyl) amino, (3-nitrophenyl) amino or (3-ethynylphenyl) amino, if R c simultaneously means tetrahydropyran -4-ylamino, tetrahydrofurfurylamino, 4-oxocyclohexylamino, cyclohexylamino, morpholino, piperidin-4-ylamino, isopropylamino, 1-methylpiperidin-4-ylamino, tert. -butylamino, N- (4-hydroxycyclohexyl) -N-methylamino, 4-hydroxycyclohexylamino, 4-aminocyclohexylamino, 4-dimethylaminocyclohexylamino, trans-4-carboxycyclohexylamino, trans-4- (pyrrolidin-1-yl) carbonylcyclohexylamino or trans-4-morpholinocarbonylcyclohexylamino group;
their taugomers, stereoisomers and salts.
за исключением следующих соединений: 4-[(4-амино-3,5-дибромфенил)амино] -6-[(транс-4-гидроксициклогексил)амино] пиримидо[5,4-d] пиримидин; 4 -[(4-амино-3,5-дихлорфенил)амино] -6-[(транс-4-гидроксициклогексил)амино] пиримидо[5,4-d] пиримидин; 4-[(4-амино-3-нитрофенил)амино]-6-[(транс-4-гидроксициклогексил)амино] пиримидо[5,4-d]пиримидин; 4-[(4-амино-3-нитрофенил)амино] -6-(мopфoлинo)пиpимидo[5,4-d] пиpимидин; 4-[(4-хлор-3-нитрофенил)амино]-6-[(транс-4-гидроксициклогексил)амино]пиримидо[5,4-d]пиримидин;
а также соединений, в которых группа RaNRb означает (3-хлорфенил)амино-, (3-нитрофенил)амино- или (3-этинилфенил)аминогруппу, если Rc одновременно означает тетрагидрофурфуриламино-, морфолино-, 1-метилпиперидин-4-иламино-, N-(4-гидроксициклогексил)-N-метиламино-, 4-гидроксицикдогексиламино-, 4-диметиламиноциклогексиламино-, транс-4-карбоксициклогексиламино-, транс-4-(пирролидин-1-ил)карбонилциклогексиламино- или транс-4-морфолинокарбонилциклогексиламиногруппу;
и соединений, в которых группа RaNRb означает (3-хлор-4-фторфенил)аминогруппу, если Rc одновременно означает 1-метилпиперидин-3-иламино-, тетрагидрофупфуриламино-, 3-(метоксикар6ониламино)проп-1-иламино-, N-метил-N-(2-гидроксиэтил)-амино-, 4-аминопиперидин-1-ильную, морфолино-, 1-метилпиперидин-4-иламино-, 4-гидроксициклогексиламино-, 4-диметиламиноциклогексиламино-, N-(4-гидроксициклогексил)-N-метиламино-, транс-4-карбоксициклогексиламино-, транс-4-(2-(морфолинокар6онил)этил)циклогексиламино-, транс-4-(пирролидин-1-ил)карбонилциклогексиламино- или транс-4-морфолинокарбонилциклогексиламиногруппу;
их таутомеры, стереоизомеры и соли.4. Pyrimido [5,4-d] pyrimidines of the general formula (I) according to claim 1, wherein R a is a hydrogen atom; R b means 3-chlorophenyl, 3-chloro-4-fluorophenyl, 3- (1,1,2,2-tetrafluoroethoxy) phenyl, 4-amino-3,5-di6romphenyl, 4-amino-3,5-dichlorophenyl, 4- (benzyl) phenyl, 3- (benzyloxy) phenyl, 4- (benzyloxy) phenyl, 3- (hydroxymethyl) phenyl, biphenyl-4-yl, 3-phenoxyphenyl, 4-phenoxyphenyl, 3-trifluoromethoxyphenyl, 3-cyanophenyl, 3-trifluoromethylphenyl, 3,4-difluorophenyl, 3-nitrophenyl, 3-ethynylphenyl, 4-amino-3-nitrophenyl, 4-chloro-3-nitrophenyl, 4- (benzyloxy) -3-chlorophenyl, 3-chloro-4- phenoxyphenyl, 3-chloro-4-cyanophenyl or 4- ENT-3-cyanophenyl group; or R a and R b together with the nitrogen atom between them mean an indolin-1-yl or 1,2,3,4-tetrahydroquinolin-1-yl group; R c means a substituted at position 4 4-hydroxyphenyl group and additionally at position 2 with a methyl group, a pyrrolidin-1-ilen group; piperidin-1-yl group unsubstituted or substituted at position 4 of amino, methylamino, hydroxyl, formylamino, methoxycarbonylamino, N-methyl-N-methylsulfonylamino, aminomethyl, morpholino, pyrrolidin-1-yl, piperazin-1 methyl, 1-methylpiperazin-4-yl, (1-methylpiperazin-4-yl) methyl, 4-dimethylaminopiperidin-1-yl, piperidin-4-yl or 1-methylpiperidin-4-yl group, 4-amino-3 an ethylpiperidin-1-yl group; 4-amino-4-methylpiperidin-1-yl group; a piperidin-1-yl group substituted at position 3 with an aminomethyl, aminocarbonyl or aminocarbonylmethyl group; A 1-azacycloheptyl or 4-amino-1-azacycloheptyl group; morpholino group; a piperazin-1-yl group substituted at the 4-position with a 2-methoxyphenyl, 3-methoxyphenyl or 4-methoxyphenyl group; homopiperazin-1-yl or 4-methyl homopiperazin-1-yl group; an 8-aza-bicyclo [3.2.1] oct-8-octyl group substituted at the 3-position by an amino or acetylamino group; or a group (R 4 NR 5 ) in which: R 4 is a hydrogen atom, a methyl or ethyl group; R 5 means a hydrogen atom; methyl group substituted with tetrahydrofur-3-yl, piperidin-4-yl, 1-methylpiperidin-4-yl, 1-tert. a butyloxycarbonylpiperidin-4-yl or quinuclidin-4-yl group; an ethyl group substituted at position 2 with a hydroxyl, amino, 4-tert.-butyloxycarbonylpiperazin-1-yl or 4- (morpholinocarbonyl) piperazin-1-yl group; 2,2-dimethoxyethyl group; a prop-1-yl group which is substituted at position 2 by an amino group and may be further substituted at position 2 by a methyl group; a prop-1-yl group substituted at position 3 with an amino group; a prop-2-yl group substituted at position 1 with a phenoxy group, 4-aminophenyl group, piperidin-1-yl group or diethylamino group; a prop-2-yl group which is substituted at position 1 by an amino group and additionally at position 2 by a methyl group; 4-aminobutyl or 5-aminopentyl group; a cyclohexyl group substituted at the 4-position with hydroxyl, dimethylamino, 1-methylpiperazin-4-yl, piperazin-1-yl-carbonyl, 1-methylpiperazin-4-yl-carbonyl, 4-dimethylaminopiperidin-1-yl, carboxyl, morpholinocarbonyl, (pyrrolidin-1-yl) carbonyl, methoxycarbonyl, aminomethyl, methylamino, methoxycarbonylamino, 2- (morpholinocarbonyl) ethyl or 2- (pyrrolidin-1-ylcarbonyl) ethyl group; a cyclohexylmethyl group substituted in the cyclohexyl part at position 4 with an amino, aminomethyl or benzyloxycarbonylamino group or at position 3 with an aminomethyl group; 1-methylpiperidin-3-yl group; a piperidin-4-yl group substituted at the 1-position with a cyano, methyl, tert.-butyloxycarbonyl, (N, N-dimethylamino) carbonyl or methoxycarbonyl group; 4-aminobenzyl group; quinuclidin-3-yl, 1-benzyl-4- (azacycloheptyl) -, 1-tert. a butyloxycarbonyl-4- (azacycloheptyl) - or 4- (azacycloheptyl) group;
with the exception of the following compounds: 4 - [(4-amino-3,5-dibromophenyl) amino] -6 - [(trans-4-hydroxycyclohexyl) amino] pyrimido [5,4-d] pyrimidine; 4 - [(4-amino-3,5-dichlorophenyl) amino] -6 - [(trans-4-hydroxycyclohexyl) amino] pyrimido [5,4-d] pyrimidine; 4 - [(4-amino-3-nitrophenyl) amino] -6 - [(trans-4-hydroxycyclohexyl) amino] pyrimido [5,4-d] pyrimidine; 4 - [(4-amino-3-nitrophenyl) amino] -6- (morpholino) pyrimido [5,4-d] pyrimidine; 4 - [(4-chloro-3-nitrophenyl) amino] -6 - [(trans-4-hydroxycyclohexyl) amino] pyrimido [5,4-d] pyrimidine;
as well as compounds in which the group R a NR b means (3-chlorophenyl) amino, (3-nitrophenyl) amino or (3-ethynylphenyl) amino group, if R c simultaneously means tetrahydrofurfurylamino, morpholino, 1-methylpiperidine 4-ylamino, N- (4-hydroxycyclohexyl) -N-methylamino, 4-hydroxycyclohexylamino, 4-dimethylaminocyclohexylamino, trans-4-carboxycyclohexylamino, trans-4- (pyrrolidin-1-yl) carbonylcyclohexylamino or trans A -4-morpholinocarbonylcyclohexylamino group;
and compounds in which the group R a NR b means a (3-chloro-4-fluorophenyl) amino group if R c simultaneously means 1-methylpiperidin-3-ylamino, tetrahydrofupfurylamino, 3- (methoxycar6onylamino) prop-1-ylamino , N-methyl-N- (2-hydroxyethyl) -amino, 4-aminopiperidin-1-yl, morpholino, 1-methylpiperidin-4-ylamino, 4-hydroxycyclohexylamino, 4-dimethylaminocyclohexylamino, N- (4 -hydroxycyclohexyl) -N-methylamino-, trans-4-carboxycyclohexylamino, trans-4- (2- (morpholinocar6onyl) ethyl) cyclohexylamino, trans-4- (pyrrolidin-1-yl) carbonylcyclohexylamino or trans-4-mor folinocarbonylcyclohexylamino group;
their tautomers, stereoisomers and salts.
и их соли.5. Pyrimido [5,4-d] pyrimidines of the general formula (I) according to claim 1, which are the following compounds: 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4-methoxycar6onylaminopiperidin-1- yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6 - [(quinuclidin-3-yl) amino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4-formylaminopiperidin-1-yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- (aminomethyl) piperidin-1-yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [1-methoxycarbonylpiperidin-4-ylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [3-aminopropylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4-aminobenzylamino] pyrimido [5,4-d] pyrimidine; 4 - [(4-amino-3,5-dichlorophenyl) amino] -6- [trans-4- (morpholinocarbonyl) cyclohexylamino] pyrimido [5,4-d] pyrimidine; 4 - [(4-amino-3,5-dichlorophenyl) amino] -6- [trans-4- (pyrrolidinocarbonyl) cyclohexylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- (piperidin-4-yl) piperidin-1-yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- (aminomethyl) cyclohexylmethylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [quinuclidin-4-ylmethylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [2-amino-2-methylprop-1-ylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [N-methyl-N- (1-methylpiperidin-4-yl) amino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [piperidin-4-ylmethylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- (morpholino) piperidin-1-yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- (pyrrolidin-1-yl) piperidin-1-yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [3- (aminomethyl) cyclohexylmethylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- (1-methylpiperidin-4-yl) piperidin-1-yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- (1-methylpiperazin-4-yl) cyclohexylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4-hydroxypiperidin-1-yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6 - [(1-cyanopiperidin-4-yl) amino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6 - [(1-methylpiperidin-4-yl) methylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [2- (4- (morpholinocarbonyl) piperazin-1-yl) ethylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4-amino-1-azacycloheptyl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- (azacycloheptyl) amino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [trans-4-aminomethylcyclohexylamino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [3-aminomethylpiperidin-1-yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- (1-methylpiperidin-4-yl) piperidin-1-yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4-amino-4-methylpiperidin-1-yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [endo-3-acetylamino-8-azabicyclo [3.2.1] oct-8-yl] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [4- (4-aminopiperidin-1-yl) methylpiperidin-1-yl] pyrimido [5,4-d] pyrimidine; 4 - [(4-benzyloxyphenyl) amino] -6- [trans-4-dimethylaminocyclohexylamino] pyrimido [5,4-d] pyrimidine; (3'S) -4- [3-chlorophenylamino] -6 - [(quinuclidin-3'-yl) amino] pyrimido [5,4-d] pyrimidine; 4 - [(3-chloro-4-fluorophenyl) amino] -6- [1-dimethylaminocarbonylpiperidin-4-yl-amino] pyrimido [5,4-d] pyrimidine; (3'S) -4 - [(3-chloro-4-fluorophenyl) amino] -6 - [(quinuclidin-3'-yl) amino] pyrimido [5,4-d] pyrimidine; (3'R) -4 - [(3-chloro-4-fluorophenyl) amino] -6 - [(quinuclidin-3'-yl) amino] pyrimido [5,4-d] pyrimidine;
and their salts.
а) соединение общей формулы II
в которой Rc имеет указанные в пп. 1-7 значения и Z1 означает удаляемую группу,
вводят во взаимодействие с амином общей формулы III
H-(RaNRb)
в которой Ra и Rb имеют указанные в пп. 1-7 значения,
или
б) для получения соединений общей формулы (I), в которой Rc означает один из указанных в пп. 1-7 для Rc остатков, связанных через атом кислорода или азота с пиримидо[5,4-d]пиримидином, соединение общей формулы IV
в которой Ra и Rb имеют указанные в пп. 1-7 значения и Z2 означает удаляемую группу,
вводят во взаимодействие с соединением общей формулы V
H-Rc
в которой Rc означает один из указанных в пп. 1-7 для Rc остатков, связанных через атом кислорода или азота с пиримидо[5,4-d]пиримидином; и, в желательном случае, таким образом полученное соединение общей формулы (I), которое содержит амино-, алкиламино- или иминогруппу, путем ацилирования или сульфонилирования переводят в соответствующее ацильное или сульфонильное соединение общей формулы (I) и/или таким образом полученное соединение общей формулы (I), которое содержит амино-, алкиламино- или иминогруппу, путем алкилирования или восстановительного алкилирования переводят в соответствующее алкильное соединение общей формулы (I) и/или таким образом полученное соединение общей формулы (I), которое содержит карбоксильную группу, путем этерификации переводят в соответствующий сложный эфир общей формулы (I) и/или таким образом полученное соединение общей формулы (I), которое содержит карбоксильную или сложноэфирную группу, путем амидирования переводят в соответствующий амид общей формулы (I) и/или таким образом полученное соединение общей формулы (I), которое содержит первичную или вторичную гидроксильную группу, путем окисления переводят в соответствующее карбонильное соединение общей формулы (I) и/или, в случае необходимости, отщепляют используемую при вышеописанных превращениях защитную группу и/или, в желательном случае, таким образом полученное соединение общей формулы (I) разделяют на его стереоизомеры и/или таким образом полученное соединение общей формулы (I) переводят в его соли, в особенности для фармацевтического применения в его физиологически приемлемые соли.12. The method of obtaining compounds of General formula (I) according to PP. 1-8, characterized in that
a) a compound of General formula II
in which R c has specified in paragraphs. 1-7 values and Z 1 means a deleted group,
enter into interaction with an amine of General formula III
H- (R a NR b )
in which R a and R b are specified in paragraphs. 1-7 values
or
b) to obtain compounds of General formula (I), in which R c means one of those specified in paragraphs. 1-7 for R c residues linked via an oxygen or nitrogen atom to pyrimido [5,4-d] pyrimidine, a compound of general formula IV
in which R a and R b are specified in paragraphs. 1-7 values and Z 2 means a deleted group,
enter into interaction with the compound of General formula V
HR c
in which R c means one of those specified in paragraphs. 1-7 for R c residues linked through an oxygen or nitrogen atom to pyrimido [5,4-d] pyrimidine; and, if desired, the thus obtained compound of general formula (I), which contains an amino, alkylamino or imino group, is converted by acylation or sulfonylation to the corresponding acyl or sulfonyl compound of general formula (I) and / or the thus obtained compound of general of formula (I), which contains an amino, alkylamino or imino group, by alkylation or reductive alkylation, is converted to the corresponding alkyl compound of the general formula (I) and / or the thus obtained compound generally of the formula (I), which contains a carboxyl group, is converted by esterification to the corresponding ester of the general formula (I) and / or the thus obtained compound of the general formula (I), which contains a carboxyl or ester group, is converted by amidation to the corresponding amide of the general formula (I) and / or the thus obtained compound of general formula (I), which contains a primary or secondary hydroxyl group, is converted by oxidation to the corresponding carbonyl compound of general formula (I) and / or, if not convergence, the protective group used in the above transformations is cleaved and / or, if desired, the thus obtained compound of the general formula (I) is separated into its stereoisomers and / or the thus obtained compound of the general formula (I) is converted into its salts, especially for pharmaceutical use in its physiologically acceptable salts.
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| DE19608588.8 | 1996-03-06 |
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| US6028183A (en) | 1997-11-07 | 2000-02-22 | Gilead Sciences, Inc. | Pyrimidine derivatives and oligonucleotides containing same |
| JP3270834B2 (en) * | 1999-01-27 | 2002-04-02 | ファイザー・プロダクツ・インク | Heteroaromatic bicyclic derivatives useful as anticancer agents |
| HK1049664B (en) | 1999-11-05 | 2006-11-10 | Genzyme Corporation | Quinazoline derivatives as vegf inhibitors |
| EP1170011A1 (en) * | 2000-07-06 | 2002-01-09 | Boehringer Ingelheim International GmbH | Novel use of inhibitors of the epidermal growth factor receptor |
| DE10115921A1 (en) | 2001-03-30 | 2002-10-02 | Boehringer Ingelheim Pharma | Process for the preparation of 4,6-diaminopyrimido [5,4-d] pyrimidines |
| EP1300146A1 (en) * | 2001-10-03 | 2003-04-09 | Boehringer Ingelheim International GmbH | Pharmaceutical composition for the treatment of animal mammary tumors |
| JPWO2003055858A1 (en) * | 2001-12-27 | 2005-05-12 | 東レ・ファインケミカル株式会社 | Method for producing 1-alkoxycarbonyl-containing saturated heterocyclic derivative |
| WO2004087707A1 (en) * | 2003-03-31 | 2004-10-14 | Vernalis (Cambridge) Limited | Pyrazolopyrimidine compounds and their use in medicine |
| BRPI0415395A (en) * | 2003-10-15 | 2006-12-12 | Osi Pharm Inc | compound, methods for inhibiting protein kinase activity and treating a patient who has a condition that is mediated by protein kinase activity, and, |
| ES2305887T3 (en) * | 2003-12-18 | 2008-11-01 | Janssen Pharmaceutica Nv | DERIVATIVES OF PIRIDO AND PYRIMIDOPIRIMIDINAS AS ANTIPROLIFERATIVE AGENTS. |
| JO3088B1 (en) * | 2004-12-08 | 2017-03-15 | Janssen Pharmaceutica Nv | Macrocyclic Quinazoline derivatives and their use as MTKI |
| NI200700147A (en) | 2004-12-08 | 2019-05-10 | Janssen Pharmaceutica Nv | QUINAZOLINE DERIVATIVES KINE INHIBITORS TARGETING MULTIP |
| KR101139038B1 (en) | 2005-06-28 | 2012-05-02 | 삼성전자주식회사 | Pyrimidopyrimidine Derivatives and Organic Thin Film Transistor Using The Same |
| EA014779B1 (en) | 2006-07-13 | 2011-02-28 | Янссен Фармацевтика Н.В. | Mtki quinazoline derivatives |
| CA2687909C (en) * | 2007-06-21 | 2015-09-15 | Janssen Pharmaceutica Nv | Indolin-2-ones and aza-indolin-2-ones |
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| DE3049207A1 (en) * | 1980-12-27 | 1982-07-29 | Dr. Karl Thomae Gmbh, 7950 Biberach | NEW TRISUBSTITUTED PYRIMIDO (5,4-D) PYRIMIDINE, THEIR PRODUCTION AND USE AS A MEDICINAL PRODUCT |
| DE4325900A1 (en) * | 1993-08-02 | 1995-02-09 | Thomae Gmbh Dr K | Trisubstituted pyrimido [5,4-d] pyrimidines for the modulation of multidrug resistance, pharmaceutical compositions containing them and methods for their preparation |
| DE4431867A1 (en) * | 1994-09-07 | 1996-03-14 | Thomae Gmbh Dr K | Pyrimido [5,4-d] pyrimidines, medicaments containing these compounds, their use and processes for their preparation |
| TW414798B (en) * | 1994-09-07 | 2000-12-11 | Thomae Gmbh Dr K | Pyrimido (5,4-d) pyrimidines, medicaments comprising these compounds, their use and processes for their preparation |
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1996
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1997
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- 1997-03-03 JP JP9531440A patent/JP2000506151A/en not_active Ceased
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- 1997-03-03 RU RU98118380/04A patent/RU2195461C2/en not_active IP Right Cessation
- 1997-03-03 TR TR1998/01755T patent/TR199801755T2/en unknown
- 1997-03-03 KR KR1019980706935A patent/KR19990087504A/en not_active Ceased
- 1997-03-03 EE EE9800278A patent/EE9800278A/en unknown
- 1997-03-03 WO PCT/EP1997/001047 patent/WO1997032880A1/en not_active Ceased
- 1997-03-03 BR BR9707839A patent/BR9707839A/en not_active Application Discontinuation
- 1997-03-03 CN CN97192784A patent/CN1064362C/en not_active Expired - Fee Related
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- 1997-03-05 AR ARP970100873A patent/AR006108A1/en unknown
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