BG106491A - Хиназолинови съединения и фармацевтични състави които ги съдържат - Google Patents

Info

Publication number

BG106491A

BG106491A BG106491A BG10649102A BG106491A BG 106491 A BG106491 A BG 106491A BG 106491 A BG106491 A BG 106491A BG 10649102 A BG10649102 A BG 10649102A BG 106491 A BG106491 A BG 106491A

Authority

BG

Bulgaria

Prior art keywords

alkyl

group

hydrogen

optionally substituted

independently

Prior art date

1999-09-21

Links

• Espacenet
• Global Dossier
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• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 8
• 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 210
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 193
• 239000001257 hydrogen Substances 0.000 claims abstract description 192
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 66
• 238000002360 preparation method Methods 0.000 claims abstract description 63
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 62
• 108090000461 Aurora Kinase A Proteins 0.000 claims abstract description 42
• 150000002148 esters Chemical class 0.000 claims abstract description 42
• 150000003839 salts Chemical class 0.000 claims abstract description 36
• 102100032311 Aurora kinase A Human genes 0.000 claims abstract description 35
• 150000001408 amides Chemical class 0.000 claims abstract description 34
• 239000003814 drug Substances 0.000 claims abstract description 18
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
• 125000000217 alkyl group Chemical group 0.000 claims description 361
• 125000000623 heterocyclic group Chemical group 0.000 claims description 126
• 150000002431 hydrogen Chemical class 0.000 claims description 113
• -1 carbamoyl-sulfonyl Chemical group 0.000 claims description 98
• 229910052736 halogen Inorganic materials 0.000 claims description 95
• 150000002367 halogens Chemical class 0.000 claims description 94
• 125000003545 alkoxy group Chemical group 0.000 claims description 91
• 229910052757 nitrogen Inorganic materials 0.000 claims description 90
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 73
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 72
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 70
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 70
• 125000000524 functional group Chemical group 0.000 claims description 66
• 125000001424 substituent group Chemical group 0.000 claims description 59
• 125000001183 hydrocarbyl group Chemical group 0.000 claims description 53
• 125000005842 heteroatom Chemical group 0.000 claims description 51
• 125000003118 aryl group Chemical group 0.000 claims description 47
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 47
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 44
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 44
• 229910052799 carbon Inorganic materials 0.000 claims description 41
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 31
• 125000003277 amino group Chemical group 0.000 claims description 31
• 125000004122 cyclic group Chemical group 0.000 claims description 28
• 125000000304 alkynyl group Chemical group 0.000 claims description 27
• 125000004043 oxo group Chemical group O=* 0.000 claims description 27
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
• 239000000651 prodrug Substances 0.000 claims description 23
• 229940002612 prodrug Drugs 0.000 claims description 23
• 229920006395 saturated elastomer Polymers 0.000 claims description 23
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 19
• 125000003342 alkenyl group Chemical group 0.000 claims description 18
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 18
• 238000000034 method Methods 0.000 claims description 18
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 17
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 17
• 239000001301 oxygen Substances 0.000 claims description 17
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 15
• 125000002947 alkylene group Chemical group 0.000 claims description 15
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 15
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
• 125000001589 carboacyl group Chemical group 0.000 claims description 15
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
• 125000004432 carbon atom Chemical group C* 0.000 claims description 14
• 239000011593 sulfur Substances 0.000 claims description 14
• 125000004423 acyloxy group Chemical group 0.000 claims description 13
• 125000003282 alkyl amino group Chemical group 0.000 claims description 12
• 125000004414 alkyl thio group Chemical group 0.000 claims description 12
• 150000001721 carbon Chemical group 0.000 claims description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
• 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 11
• 229910052731 fluorine Inorganic materials 0.000 claims description 11
• 239000011737 fluorine Substances 0.000 claims description 11
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 10
• 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 description 10
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 10
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 9
• 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 8
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
• 241001465754 Metazoa Species 0.000 claims description 8
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 8
• 125000004849 alkoxymethyl group Chemical group 0.000 claims description 8
• 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 8
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 8
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
• 125000001153 fluoro group Chemical group F* 0.000 claims description 7
• 125000004193 piperazinyl group Chemical group 0.000 claims description 7
• 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 7
• 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 6
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 6
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 6
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
• 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 5
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
• 230000002401 inhibitory effect Effects 0.000 claims description 5
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
• HFFXLYHRNRKAPM-UHFFFAOYSA-N 2,4,5-trichloro-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C(=CC(Cl)=C(Cl)C=2)Cl)=N1 HFFXLYHRNRKAPM-UHFFFAOYSA-N 0.000 claims description 4
• 125000004450 alkenylene group Chemical group 0.000 claims description 4
• 125000004419 alkynylene group Chemical group 0.000 claims description 4
• 125000000751 azo group Chemical group [*]N=N[*] 0.000 claims description 4
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 3
• 230000029936 alkylation Effects 0.000 claims description 3
• 238000005804 alkylation reaction Methods 0.000 claims description 3
• 125000001072 heteroaryl group Chemical group 0.000 claims description 3
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 2
• 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 2
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
• 125000004104 aryloxy group Chemical group 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
• 125000006413 ring segment Chemical group 0.000 claims description 2
• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• 125000003396 thiol group Chemical class [H]S* 0.000 claims description 2
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 3
• 150000001336 alkenes Chemical class 0.000 claims 1
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
• 125000005505 thiomorpholino group Chemical group 0.000 claims 1
• 206010028980 Neoplasm Diseases 0.000 abstract description 17
• 201000011510 cancer Diseases 0.000 abstract description 11
• 230000005764 inhibitory process Effects 0.000 abstract description 7
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 4
• 239000007787 solid Substances 0.000 description 109
• 238000006243 chemical reaction Methods 0.000 description 100
• 238000005160 1H NMR spectroscopy Methods 0.000 description 65
• 239000007858 starting material Substances 0.000 description 58
• 239000000243 solution Substances 0.000 description 57
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
• 210000004027 cell Anatomy 0.000 description 41
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
• 239000000203 mixture Substances 0.000 description 31
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• 239000002904 solvent Substances 0.000 description 16
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
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• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
• 238000000746 purification Methods 0.000 description 14
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