PT1278735E - 2,4-di(hetero-)arilamino(-oxi)-pirimidinas substituídas na posição 5 como agentes antineoplásicos - Google Patents

Info

Publication number

PT1278735E

PT1278735E PT01906021T PT01906021T PT1278735E PT 1278735 E PT1278735 E PT 1278735E PT 01906021 T PT01906021 T PT 01906021T PT 01906021 T PT01906021 T PT 01906021T PT 1278735 E PT1278735 E PT 1278735E

Authority

PT

Portugal

Prior art keywords

alkyl

amino

optionally substituted

substituted

heterocyclic group

Prior art date

2000-03-01

Links

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• 150000003230 pyrimidines Chemical class 0.000 title claims abstract description 45
• 239000002246 antineoplastic agent Substances 0.000 title description 4
• 229940034982 antineoplastic agent Drugs 0.000 title description 2
• 125000001769 aryl amino group Chemical group 0.000 title 1
• 238000000034 method Methods 0.000 claims abstract description 104
• 150000003839 salts Chemical class 0.000 claims abstract description 46
• 150000002148 esters Chemical class 0.000 claims abstract description 40
• 238000001727 in vivo Methods 0.000 claims abstract description 38
• 230000008569 process Effects 0.000 claims abstract description 19
• 238000004519 manufacturing process Methods 0.000 claims abstract description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
• -1 amino, phenyl Chemical group 0.000 claims description 190
• 125000000217 alkyl group Chemical group 0.000 claims description 87
• 150000001875 compounds Chemical class 0.000 claims description 76
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 72
• 229910052757 nitrogen Inorganic materials 0.000 claims description 69
• 125000000623 heterocyclic group Chemical group 0.000 claims description 58
• 125000001424 substituent group Chemical group 0.000 claims description 42
• 229910052799 carbon Inorganic materials 0.000 claims description 39
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 39
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 38
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 36
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 28
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
• 125000005843 halogen group Chemical group 0.000 claims description 25
• 125000003545 alkoxy group Chemical group 0.000 claims description 23
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 23
• 125000000304 alkynyl group Chemical group 0.000 claims description 20
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 19
• 125000003342 alkenyl group Chemical group 0.000 claims description 18
• 230000002401 inhibitory effect Effects 0.000 claims description 18
• 125000003118 aryl group Chemical group 0.000 claims description 17
• 125000003282 alkyl amino group Chemical group 0.000 claims description 16
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 16
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 14
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 14
• 125000004429 atom Chemical group 0.000 claims description 13
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 12
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 10
• 241001465754 Metazoa Species 0.000 claims description 10
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 10
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
• 239000001257 hydrogen Substances 0.000 claims description 10
• 229910052739 hydrogen Inorganic materials 0.000 claims description 10
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 9
• 125000002619 bicyclic group Chemical group 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 9
• 125000002950 monocyclic group Chemical group 0.000 claims description 9
• 238000002360 preparation method Methods 0.000 claims description 9
• 125000004076 pyridyl group Chemical group 0.000 claims description 9
• 230000001093 anti-cancer Effects 0.000 claims description 8
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
• 125000001072 heteroaryl group Chemical group 0.000 claims description 8
• 229910052717 sulfur Inorganic materials 0.000 claims description 8
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 7
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
• 230000001028 anti-proliverative effect Effects 0.000 claims description 7
• 239000000460 chlorine Substances 0.000 claims description 7
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
• 239000011593 sulfur Substances 0.000 claims description 7
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 6
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
• 229910052760 oxygen Inorganic materials 0.000 claims description 6
• 239000001301 oxygen Substances 0.000 claims description 6
• 229920006395 saturated elastomer Polymers 0.000 claims description 6
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 5
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
• 229910052794 bromium Inorganic materials 0.000 claims description 5
• 229910052801 chlorine Inorganic materials 0.000 claims description 5
• 125000001153 fluoro group Chemical group F* 0.000 claims description 5
• 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 4
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 4
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 3
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 3
• 125000004423 acyloxy group Chemical group 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims description 3
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
• 229940123587 Cell cycle inhibitor Drugs 0.000 claims description 2
• 230000006882 induction of apoptosis Effects 0.000 claims description 2
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
• 229910052705 radium Inorganic materials 0.000 claims description 2
• 229910052702 rhenium Inorganic materials 0.000 claims description 2
• 229910052703 rhodium Inorganic materials 0.000 claims description 2
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims description 2
• 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims 4
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 3
• PIEMJWXGWDBCMN-UHFFFAOYSA-N 2-[4-[(4-anilino-5-bromopyrimidin-2-yl)amino]phenoxy]acetic acid Chemical compound C1=CC(OCC(=O)O)=CC=C1NC1=NC=C(Br)C(NC=2C=CC=CC=2)=N1 PIEMJWXGWDBCMN-UHFFFAOYSA-N 0.000 claims 1
• WOWFEFJKHWCYLY-UHFFFAOYSA-N 4-n-[5-bromo-4-(6-methylpyridin-2-yl)pyrimidin-2-yl]-1-n-(2-piperidin-1-ylethyl)benzene-1,4-diamine Chemical compound CC1=CC=CC(C=2C(=CN=C(NC=3C=CC(NCCN4CCCCC4)=CC=3)N=2)Br)=N1 WOWFEFJKHWCYLY-UHFFFAOYSA-N 0.000 claims 1
• DUPNQUDKGLFCEW-UHFFFAOYSA-N 5-bromo-2-n-[4-(1-methylpiperidin-4-yl)oxyphenyl]-4-n-phenylpyrimidine-2,4-diamine Chemical compound C1CN(C)CCC1OC(C=C1)=CC=C1NC1=NC=C(Br)C(NC=2C=CC=CC=2)=N1 DUPNQUDKGLFCEW-UHFFFAOYSA-N 0.000 claims 1
• FLYWDADPUYSEFG-UHFFFAOYSA-N 5-bromo-2-n-[4-[2-(dimethylamino)ethoxy]phenyl]-4-n-phenylpyrimidine-2,4-diamine Chemical compound C1=CC(OCCN(C)C)=CC=C1NC1=NC=C(Br)C(NC=2C=CC=CC=2)=N1 FLYWDADPUYSEFG-UHFFFAOYSA-N 0.000 claims 1
• ARBYNWNBIKVNNJ-UHFFFAOYSA-N 5-bromo-2-n-[4-[3-(methylamino)prop-1-ynyl]phenyl]-4-n-phenylpyrimidine-2,4-diamine Chemical compound C1=CC(C#CCNC)=CC=C1NC1=NC=C(Br)C(NC=2C=CC=CC=2)=N1 ARBYNWNBIKVNNJ-UHFFFAOYSA-N 0.000 claims 1
• VGDBUSCPHQFLTB-UHFFFAOYSA-N 5-bromo-4-n-phenyl-2-n-[4-[2-(propan-2-ylamino)ethylamino]phenyl]pyrimidine-2,4-diamine Chemical compound C1=CC(NCCNC(C)C)=CC=C1NC1=NC=C(Br)C(NC=2C=CC=CC=2)=N1 VGDBUSCPHQFLTB-UHFFFAOYSA-N 0.000 claims 1
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• 210000004027 cell Anatomy 0.000 description 36
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