NO328804B1 - Nye dihydropterinoner, fremgangsmate for deres fremstilling og deres anvendelse - Google Patents
Nye dihydropterinoner, fremgangsmate for deres fremstilling og deres anvendelse Download PDFInfo
- Publication number
- NO328804B1 NO328804B1 NO20040680A NO20040680A NO328804B1 NO 328804 B1 NO328804 B1 NO 328804B1 NO 20040680 A NO20040680 A NO 20040680A NO 20040680 A NO20040680 A NO 20040680A NO 328804 B1 NO328804 B1 NO 328804B1
- Authority
- NO
- Norway
- Prior art keywords
- alkyl
- optionally substituted
- group
- cycloalkyl
- heteroaryl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 17
- 238000002360 preparation method Methods 0.000 title claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 90
- 239000001257 hydrogen Substances 0.000 claims description 45
- 229910052739 hydrogen Inorganic materials 0.000 claims description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 38
- 125000001424 substituent group Chemical group 0.000 claims description 38
- -1 -OCHF2 Chemical group 0.000 claims description 35
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
- 125000001072 heteroaryl group Chemical group 0.000 claims description 30
- 239000000460 chlorine Substances 0.000 claims description 26
- 229910052801 chlorine Inorganic materials 0.000 claims description 26
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 25
- 125000003118 aryl group Chemical group 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 20
- 229910052731 fluorine Inorganic materials 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 239000011737 fluorine Substances 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 19
- 229920006395 saturated elastomer Polymers 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 17
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 150000002431 hydrogen Chemical group 0.000 claims description 13
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 8
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 8
- 125000003107 substituted aryl group Chemical group 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 239000000969 carrier Substances 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- 239000005864 Sulphur Chemical group 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 4
- 230000001028 anti-proliverative effect Effects 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 3
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 208000015181 infectious disease Diseases 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 230000002757 inflammatory effect Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 1
- 101100134927 Gallus gallus COR8 gene Proteins 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 108
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- 210000004027 cell Anatomy 0.000 description 34
- 239000013078 crystal Substances 0.000 description 30
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 125000000217 alkyl group Chemical group 0.000 description 20
- 239000013543 active substance Substances 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000003208 petroleum Substances 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000003085 diluting agent Substances 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 235000011181 potassium carbonates Nutrition 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 108091000080 Phosphotransferase Proteins 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000012362 glacial acetic acid Substances 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- 102000020233 phosphotransferase Human genes 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- 230000004668 G2/M phase Effects 0.000 description 7
- 239000005909 Kieselgur Substances 0.000 description 7
- 230000022131 cell cycle Effects 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 229920002261 Corn starch Polymers 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000012317 TBTU Substances 0.000 description 5
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- 229940099112 cornstarch Drugs 0.000 description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 150000002828 nitro derivatives Chemical class 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 239000000454 talc Substances 0.000 description 5
- 235000012222 talc Nutrition 0.000 description 5
- 229910052623 talc Inorganic materials 0.000 description 5
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- INUSQTPGSHFGHM-UHFFFAOYSA-N 2,4-dichloro-5-nitropyrimidine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1Cl INUSQTPGSHFGHM-UHFFFAOYSA-N 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 4
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- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 238000005576 amination reaction Methods 0.000 description 4
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- 239000008346 aqueous phase Substances 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
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- 239000007924 injection Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
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- 229910052742 iron Inorganic materials 0.000 description 4
- 239000002480 mineral oil Substances 0.000 description 4
- 235000010446 mineral oil Nutrition 0.000 description 4
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- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 4
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- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 4
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 4
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- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 3
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- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10143272 | 2001-09-04 | ||
| PCT/EP2002/009728 WO2003020722A1 (de) | 2001-09-04 | 2002-08-30 | Neue dihydropteridinone, verfahren zu deren herstellung und deren verwendung als arzneimittel |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20040680L NO20040680L (no) | 2004-02-16 |
| NO20040680D0 NO20040680D0 (no) | 2004-02-16 |
| NO328804B1 true NO328804B1 (no) | 2010-05-18 |
Family
ID=7697637
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20040680A NO328804B1 (no) | 2001-09-04 | 2004-02-16 | Nye dihydropterinoner, fremgangsmate for deres fremstilling og deres anvendelse |
Country Status (30)
| Country | Link |
|---|---|
| EP (1) | EP1427730B1 (es) |
| JP (1) | JP3876254B2 (es) |
| KR (1) | KR100955589B1 (es) |
| CN (1) | CN1551881A (es) |
| AR (1) | AR036586A1 (es) |
| AT (1) | ATE332898T1 (es) |
| AU (1) | AU2002337047B2 (es) |
| BR (1) | BRPI0212137A2 (es) |
| CA (1) | CA2458699C (es) |
| CO (1) | CO5560575A2 (es) |
| CY (1) | CY1105337T1 (es) |
| DE (1) | DE50207522D1 (es) |
| DK (1) | DK1427730T3 (es) |
| EA (1) | EA007062B1 (es) |
| EC (1) | ECSP045003A (es) |
| ES (1) | ES2268093T3 (es) |
| HR (1) | HRP20040213A2 (es) |
| HU (1) | HUP0401293A3 (es) |
| IL (2) | IL160440A0 (es) |
| MX (1) | MXPA04002067A (es) |
| MY (1) | MY129751A (es) |
| NO (1) | NO328804B1 (es) |
| NZ (1) | NZ531928A (es) |
| PL (1) | PL369740A1 (es) |
| PT (1) | PT1427730E (es) |
| RS (1) | RS51012B (es) |
| UA (1) | UA76512C2 (es) |
| UY (1) | UY27427A1 (es) |
| WO (1) | WO2003020722A1 (es) |
| ZA (1) | ZA200401365B (es) |
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| NZ516610A (en) | 1999-08-04 | 2004-05-28 | Icagen Inc | Benzanilides as potassium channel openers |
| US6495550B2 (en) * | 1999-08-04 | 2002-12-17 | Icagen, Inc. | Pyridine-substituted benzanilides as potassium ion channel openers |
| MXPA05009068A (es) * | 2003-02-26 | 2005-10-19 | Boehringer Ingelheim Pharma | Dihidro-pteridinonas, metodo para la produccion y uso del mismo en la forma de farmacos. |
| US6861422B2 (en) | 2003-02-26 | 2005-03-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Dihydropteridinones, processes for preparing them and their use as pharmaceutical compositions |
| DE102004029784A1 (de) * | 2004-06-21 | 2006-01-05 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue 2-Benzylaminodihydropteridinone, Verfahren zur deren Herstellung und deren Verwendung als Arzneimittel |
| DE102004033670A1 (de) | 2004-07-09 | 2006-02-02 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Pyridodihydropyrazinone, Verfahren zu Ihrer Herstellung und Ihre Verwendung als Arzneimittel |
| US20060058311A1 (en) | 2004-08-14 | 2006-03-16 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation |
| US7728134B2 (en) | 2004-08-14 | 2010-06-01 | Boehringer Ingelheim International Gmbh | Hydrates and polymorphs of 4[[(7R)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-pteridinyl]amino]-3-methoxy-N-(1-methyl-4-piperidinyl)-benzamide, process for their manufacture and their use as medicament |
| US20060035903A1 (en) * | 2004-08-14 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Storage stable perfusion solution for dihydropteridinones |
| US20060074088A1 (en) | 2004-08-14 | 2006-04-06 | Boehringer Ingelheim International Gmbh | Dihydropteridinones for the treatment of cancer diseases |
| US7759485B2 (en) * | 2004-08-14 | 2010-07-20 | Boehringer Ingelheim International Gmbh | Process for the manufacture of dihydropteridinones |
| EP1632493A1 (de) | 2004-08-25 | 2006-03-08 | Boehringer Ingelheim Pharma GmbH & Co.KG | Dihydropteridinonderivative, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
| EP1630163A1 (de) | 2004-08-25 | 2006-03-01 | Boehringer Ingelheim Pharma GmbH & Co.KG | Dihydropteridinonderivative, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
| EP1784406A1 (de) | 2004-08-27 | 2007-05-16 | Boehringer Ingelheim International GmbH | Dihydropteridinone, verfahren zu deren herstellung und deren verwendung als arzneimittel |
| DE102004058337A1 (de) | 2004-12-02 | 2006-06-14 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung von annelierten Piperazin-2-on Derivaten |
| WO2007014838A1 (en) * | 2005-08-03 | 2007-02-08 | Boehringer Ingelheim International Gmbh | Dihydropteridinones in the treatment of respiratory diseases |
| US7439358B2 (en) * | 2006-02-08 | 2008-10-21 | Boehringer Ingelheim International Gmbh | Specific salt, anhydrous and crystalline form of a dihydropteridione derivative |
| KR20080095902A (ko) | 2006-02-14 | 2008-10-29 | 버텍스 파마슈티칼스 인코포레이티드 | 단백질 키나제의 억제제로서 유용한 디하이드로디아제핀 |
| EP2029599A1 (en) * | 2006-05-19 | 2009-03-04 | Astra Zeneca AB | Dihydropteridine compounds as anti proliferative agents |
| TW200808325A (en) | 2006-07-06 | 2008-02-16 | Astrazeneca Ab | Novel compounds |
| WO2008009909A1 (en) * | 2006-07-17 | 2008-01-24 | Astrazeneca Ab | Pteridimones as modulators of polo-like kinase |
| WO2008040951A1 (en) * | 2006-10-03 | 2008-04-10 | Astrazeneca Ab | Compounds |
| MX337906B (es) * | 2006-10-19 | 2016-03-28 | Signal Pharm Llc | Compuestos de heteroarilo, composiciones de los mismos, y su uso como inhibidores de proteina cinasas. |
| EP1953163A1 (en) * | 2007-02-01 | 2008-08-06 | Boehringer Ingelheim Pharma GmbH & Co. KG | Pteridinone derivatives as PI3-kinases inhibitors |
| ATE524472T1 (de) * | 2007-03-22 | 2011-09-15 | Takeda Pharmaceutical | Als plk1-inhibitoren geeignete substituierte pyrimidodiazepine |
| WO2008157235A1 (en) * | 2007-06-13 | 2008-12-24 | University Of Virginia Patent Foundation | Rsk inhibitors as anti-septicemia agents |
| WO2009019205A1 (en) | 2007-08-03 | 2009-02-12 | Boehringer Ingelheim International Gmbh | Crystalline form of a dihydropteridione derivative |
| EP2190849B1 (en) * | 2007-08-15 | 2013-11-20 | Vertex Pharmceuticals Incorporated | 4-(9-(3,3-difluorocyclopentyl)-5,7,7-trimethyl-6-oxo-6,7,8,9-tetrahydro-5h-pyrimido[4,5-b[1,4]diazepin-2-ylamino)-3-methoxybenzamide derivatives as inhibitors of the human protein kinases plk1 to plk4 for the treatment of proliferative diseases |
| CN101917995A (zh) | 2007-09-25 | 2010-12-15 | 武田药品工业株式会社 | Polo样激酶抑制剂 |
| EP2215091B1 (en) * | 2007-12-04 | 2016-03-30 | Nerviano Medical Sciences S.r.l. | Substituted dihydropteridin-6-one derivatives, process for their preparation and their use as kinase inhibitors |
| WO2009111868A1 (en) | 2008-03-11 | 2009-09-17 | University Health Network | Method of treating cancer using a neuropeptide y 5r (np y5r) antagonist |
| EP2100894A1 (en) | 2008-03-12 | 2009-09-16 | 4Sc Ag | Pyridopyrimidines used as Plk1 (polo-like kinase) inhibitors |
| EP2112152A1 (en) | 2008-04-22 | 2009-10-28 | GPC Biotech AG | Dihydropteridinones as Plk Inhibitors |
| GB0807452D0 (en) * | 2008-04-24 | 2008-05-28 | Chroma Therapeutics Ltd | PLK inhibitors |
| US8093043B2 (en) | 2008-06-04 | 2012-01-10 | New York University | β-TrCP1, β-TrCP2 and RSK1 or RSK2 inhibitors and methods for sensitizing target cells to apoptosis |
| WO2009153197A1 (en) | 2008-06-18 | 2009-12-23 | F. Hoffmann-La Roche Ag | Halo-substituted pyrimidodiazepines as plkl inhibitors |
| US8110578B2 (en) | 2008-10-27 | 2012-02-07 | Signal Pharmaceuticals, Llc | Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway |
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| ES2661850T3 (es) | 2009-09-14 | 2018-04-04 | Gilead Sciences, Inc. | Moduladores de receptores del tipo toll |
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| RU2012116525A (ru) | 2009-09-25 | 2013-10-27 | Вертекс Фармасьютикалз Инкорпорейтед | Способы получения перемидиновых производных, пригодных в качестве ингибиторов протеинкиназ |
| RU2012116526A (ru) | 2009-09-25 | 2013-10-27 | Вертекс Фармасьютикалз Инкорпорейтед | Способы получения производных пиримидина, применимых в качестве ингибиторов протеинкиназы |
| SG10201500511TA (en) | 2009-10-26 | 2015-03-30 | Signal Pharm Llc | Methods Of Synthesis And Purification Of Heteroaryl Compounds |
| EP2325185A1 (en) | 2009-10-28 | 2011-05-25 | GPC Biotech AG | Plk inhibitor |
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| EP2536725B1 (en) | 2010-02-17 | 2015-10-28 | Boehringer Ingelheim International GmbH | Dihydropteridinones, method for production and use thereof |
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| US9358233B2 (en) | 2010-11-29 | 2016-06-07 | Boehringer Ingelheim International Gmbh | Method for treating acute myeloid leukemia |
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