NO326133B1 - 6-substituerte pyrido-pyrimidiner, fremgangsmate for fremstilling av slike, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom - Google Patents

6-substituerte pyrido-pyrimidiner, fremgangsmate for fremstilling av slike, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom Download PDF

Info

Publication number: NO326133B1
Authority: NO; Norway
Prior art keywords: alkyl; group; mmol; substituents selected; phenyl
Prior art date: 2001-02-12

Application number

NO20033540A

Other languages

English (en)

Norwegian (no)

Other versions

NO20033540D0 (no

NO20033540L (no

Inventor

James Patrick Dunn

David Michael Goldstein

Jeffrey Jian Chen

Christophe Martin Stahl

Original Assignee

Hoffmann La Roche

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2001-02-12

Filing date

2003-08-11

Publication date

2008-10-06

2003-08-11 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

2003-08-11 Publication of NO20033540D0 publication Critical patent/NO20033540D0/no

2003-08-11 Publication of NO20033540L publication Critical patent/NO20033540L/no

2008-10-06 Publication of NO326133B1 publication Critical patent/NO326133B1/no

Links

238000002360 preparation method Methods 0.000 title claims description 226
-1 6-substituted pyrido-pyrimidines Chemical class 0.000 title claims description 172
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 39
238000000034 method Methods 0.000 title claims description 33
238000004519 manufacturing process Methods 0.000 title claims description 16
239000003814 drug Substances 0.000 title claims description 14
201000010099 disease Diseases 0.000 title description 25
239000000825 pharmaceutical preparation Substances 0.000 title description 8
150000001875 compounds Chemical class 0.000 claims description 203
125000001424 substituent group Chemical group 0.000 claims description 88
150000001412 amines Chemical class 0.000 claims description 81
229910052739 hydrogen Inorganic materials 0.000 claims description 64
239000001257 hydrogen Substances 0.000 claims description 64
125000000217 alkyl group Chemical group 0.000 claims description 61
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 50
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 42
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 40
229910052736 halogen Inorganic materials 0.000 claims description 36
150000002367 halogens Chemical group 0.000 claims description 35
150000003839 salts Chemical class 0.000 claims description 35
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 31
102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 28
108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims description 28
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
150000002431 hydrogen Chemical class 0.000 claims description 26
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 24
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 21
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 15
230000001404 mediated effect Effects 0.000 claims description 14
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 13
125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 13
125000003545 alkoxy group Chemical group 0.000 claims description 12
125000001544 thienyl group Chemical group 0.000 claims description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 7
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 6
125000002541 furyl group Chemical group 0.000 claims description 6
125000000842 isoxazolyl group Chemical group 0.000 claims description 6
125000004076 pyridyl group Chemical group 0.000 claims description 6
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 5
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 5
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 5
239000000654 additive Substances 0.000 claims description 5
230000000996 additive effect Effects 0.000 claims description 5
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 5
125000002757 morpholinyl group Chemical group 0.000 claims description 5
125000004193 piperazinyl group Chemical group 0.000 claims description 5
125000003386 piperidinyl group Chemical group 0.000 claims description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
208000024827 Alzheimer disease Diseases 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
208000011231 Crohn disease Diseases 0.000 claims description 3
208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 3
201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 3
206010003246 arthritis Diseases 0.000 claims description 3
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 3
208000002551 irritable bowel syndrome Diseases 0.000 claims description 3
230000001590 oxidative effect Effects 0.000 claims description 3
229910052702 rhenium Inorganic materials 0.000 claims description 3
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
238000010534 nucleophilic substitution reaction Methods 0.000 claims description 2
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 462
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 329
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 260
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 218
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 161
239000000203 mixture Substances 0.000 description 156
239000000243 solution Substances 0.000 description 144
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 132
239000011541 reaction mixture Substances 0.000 description 130
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 123
235000019439 ethyl acetate Nutrition 0.000 description 121
239000007787 solid Substances 0.000 description 116
150000003457 sulfones Chemical class 0.000 description 116
239000000047 product Substances 0.000 description 87
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 83
238000004949 mass spectrometry Methods 0.000 description 77
238000001914 filtration Methods 0.000 description 73
230000002829 reductive effect Effects 0.000 description 68
239000002904 solvent Substances 0.000 description 66
238000001704 evaporation Methods 0.000 description 65
230000008020 evaporation Effects 0.000 description 64
239000012267 brine Substances 0.000 description 62
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 62
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
238000006243 chemical reaction Methods 0.000 description 59
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 58
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 58
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 56
238000001035 drying Methods 0.000 description 53
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 52
239000002244 precipitate Substances 0.000 description 48
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 47
238000003756 stirring Methods 0.000 description 46
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
239000000460 chlorine Substances 0.000 description 35
238000004440 column chromatography Methods 0.000 description 35
239000000725 suspension Substances 0.000 description 32
125000000753 cycloalkyl group Chemical group 0.000 description 31
238000002955 isolation Methods 0.000 description 30
229910052943 magnesium sulfate Inorganic materials 0.000 description 29
235000019341 magnesium sulphate Nutrition 0.000 description 29
229910000027 potassium carbonate Inorganic materials 0.000 description 29
235000011181 potassium carbonates Nutrition 0.000 description 28
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 26
229920006395 saturated elastomer Polymers 0.000 description 25
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
102100040247 Tumor necrosis factor Human genes 0.000 description 24
239000012044 organic layer Substances 0.000 description 23
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
239000012043 crude product Substances 0.000 description 22
239000010410 layer Substances 0.000 description 22
235000017557 sodium bicarbonate Nutrition 0.000 description 21
229910000030 sodium bicarbonate Inorganic materials 0.000 description 21
238000005406 washing Methods 0.000 description 21
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
238000004809 thin layer chromatography Methods 0.000 description 18
125000001316 cycloalkyl alkyl group Chemical group 0.000 description 17
KUABOYVOOBOICM-UHFFFAOYSA-N 2-methyl-4-(methylamino)pyrimidine-5-carbothialdehyde Chemical compound CNC1=NC(C)=NC=C1C=S KUABOYVOOBOICM-UHFFFAOYSA-N 0.000 description 15
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 15
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 14
229910004298 SiO 2 Inorganic materials 0.000 description 13
125000004663 dialkyl amino group Chemical group 0.000 description 13
AHVQYHFYQWKUKB-UHFFFAOYSA-N oxan-4-amine Chemical compound NC1CCOCC1 AHVQYHFYQWKUKB-UHFFFAOYSA-N 0.000 description 13
235000010265 sodium sulphite Nutrition 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
239000002253 acid Substances 0.000 description 12
125000000623 heterocyclic group Chemical group 0.000 description 12
230000003647 oxidation Effects 0.000 description 12
238000007254 oxidation reaction Methods 0.000 description 12
238000000746 purification Methods 0.000 description 12
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 11
125000001188 haloalkyl group Chemical group 0.000 description 11
125000004404 heteroalkyl group Chemical group 0.000 description 11
239000012071 phase Substances 0.000 description 11
238000010992 reflux Methods 0.000 description 11
150000003462 sulfoxides Chemical class 0.000 description 11
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
108060008682 Tumor Necrosis Factor Proteins 0.000 description 10
208000035475 disorder Diseases 0.000 description 10
229910052938 sodium sulfate Inorganic materials 0.000 description 10
235000011152 sodium sulphate Nutrition 0.000 description 10
MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 9
WDHAAJIGSXNPFO-UHFFFAOYSA-N 8h-pyrido[2,3-d]pyrimidin-7-one Chemical compound N1=CN=C2NC(=O)C=CC2=C1 WDHAAJIGSXNPFO-UHFFFAOYSA-N 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
150000002148 esters Chemical class 0.000 description 9
LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 9
125000006239 protecting group Chemical group 0.000 description 9
125000006413 ring segment Chemical group 0.000 description 9
239000002002 slurry Substances 0.000 description 9
ZBMSFARLXYLDRN-UHFFFAOYSA-N 6-amino-2-sulfanylidene-1h-pyrimidine-5-carbaldehyde Chemical compound NC1=NC(S)=NC=C1C=O ZBMSFARLXYLDRN-UHFFFAOYSA-N 0.000 description 8
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
102000004127 Cytokines Human genes 0.000 description 8
108090000695 Cytokines Proteins 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
125000002947 alkylene group Chemical group 0.000 description 8
239000007864 aqueous solution Substances 0.000 description 8
229940079593 drug Drugs 0.000 description 8
125000001072 heteroaryl group Chemical group 0.000 description 8
239000012299 nitrogen atmosphere Substances 0.000 description 8
239000012074 organic phase Substances 0.000 description 8
239000000843 powder Substances 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
239000011734 sodium Substances 0.000 description 8
108091003079 Bovine Serum Albumin Proteins 0.000 description 7
108010002352 Interleukin-1 Proteins 0.000 description 7
102000000589 Interleukin-1 Human genes 0.000 description 7
241000124008 Mammalia Species 0.000 description 7
239000007832 Na2SO4 Substances 0.000 description 7
239000002585 base Substances 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
239000012458 free base Substances 0.000 description 7
238000004128 high performance liquid chromatography Methods 0.000 description 7
125000002768 hydroxyalkyl group Chemical group 0.000 description 7
MCUICEQLBVRIIY-UHFFFAOYSA-N methyl 2-(2-fluorophenoxy)acetate Chemical compound COC(=O)COC1=CC=CC=C1F MCUICEQLBVRIIY-UHFFFAOYSA-N 0.000 description 7
238000012746 preparative thin layer chromatography Methods 0.000 description 7
239000000651 prodrug Substances 0.000 description 7
229940002612 prodrug Drugs 0.000 description 7
239000003039 volatile agent Substances 0.000 description 7
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
108091000080 Phosphotransferase Proteins 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
229940098773 bovine serum albumin Drugs 0.000 description 6
125000004432 carbon atom Chemical group C* 0.000 description 6
239000002158 endotoxin Substances 0.000 description 6
239000007788 liquid Substances 0.000 description 6
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
102000020233 phosphotransferase Human genes 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
125000002252 acyl group Chemical group 0.000 description 5
125000004442 acylamino group Chemical group 0.000 description 5
150000001299 aldehydes Chemical class 0.000 description 5
125000003118 aryl group Chemical group 0.000 description 5
229910052799 carbon Inorganic materials 0.000 description 5
239000000969 carrier Substances 0.000 description 5
210000004027 cell Anatomy 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
239000003112 inhibitor Substances 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
229920006008 lipopolysaccharide Polymers 0.000 description 5
239000012280 lithium aluminium hydride Substances 0.000 description 5
238000001819 mass spectrum Methods 0.000 description 5
230000004048 modification Effects 0.000 description 5
238000012986 modification Methods 0.000 description 5
239000003921 oil Substances 0.000 description 5
235000019198 oils Nutrition 0.000 description 5
239000003960 organic solvent Substances 0.000 description 5
229920005989 resin Polymers 0.000 description 5
239000011347 resin Substances 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
239000000126 substance Substances 0.000 description 5
OWYHAYAJHNQBGG-UHFFFAOYSA-N tert-butyl 3-oxospiro[2h-indene-1,4'-piperidine]-1'-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11C2=CC=CC=C2C(=O)C1 OWYHAYAJHNQBGG-UHFFFAOYSA-N 0.000 description 5
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
PDNZJLMPXLQDPL-UHFFFAOYSA-N (1-aminocyclopentyl)methanol Chemical compound OCC1(N)CCCC1 PDNZJLMPXLQDPL-UHFFFAOYSA-N 0.000 description 4
FLQSRSQNICPZIH-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-amine Chemical compound CS(=O)(=O)N1CCC(N)CC1 FLQSRSQNICPZIH-UHFFFAOYSA-N 0.000 description 4
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
IMLXLGZJLAOKJN-UHFFFAOYSA-N 4-aminocyclohexan-1-ol Chemical compound NC1CCC(O)CC1 IMLXLGZJLAOKJN-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
239000004215 Carbon black (E152) Substances 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 4
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 4
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CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
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LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
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JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000012546 transfer Methods 0.000 description 1
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125000004665 trialkylsilyl group Chemical group 0.000 description 1
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125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
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LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
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230000009385 viral infection Effects 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
238000005303 weighing Methods 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Immunology (AREA)
Dermatology (AREA)
Rheumatology (AREA)
Cardiology (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Heart & Thoracic Surgery (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Pulmonology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

NO20033540A 2001-02-12 2003-08-11 6-substituerte pyrido-pyrimidiner, fremgangsmate for fremstilling av slike, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom NO326133B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US26837501P	2001-02-12	2001-02-12
US33465401P	2001-11-30	2001-11-30
PCT/EP2002/001106 WO2002064594A2 (en)	2001-02-12	2002-02-04	6-substituted pyrido-pyrimidines

Publications (3)

Publication Number	Publication Date
NO20033540D0 NO20033540D0 (no)	2003-08-11
NO20033540L NO20033540L (no)	2003-08-11
NO326133B1 true NO326133B1 (no)	2008-10-06

Family

ID=26953040

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20033540A NO326133B1 (no)	2001-02-12	2003-08-11	6-substituerte pyrido-pyrimidiner, fremgangsmate for fremstilling av slike, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom

Country Status (32)

Country	Link
US (3)	US6696566B2 (es)
EP (1)	EP1361880B1 (es)
JP (1)	JP4064818B2 (es)
KR (1)	KR100639772B1 (es)
CN (1)	CN100376571C (es)
AR (1)	AR035854A1 (es)
AT (1)	ATE305303T1 (es)
AU (1)	AU2002256615B2 (es)
BR (1)	BRPI0207172B8 (es)
CA (1)	CA2434834C (es)
CZ (1)	CZ20032416A3 (es)
DE (1)	DE60206363T2 (es)
DK (1)	DK1361880T3 (es)
ES (1)	ES2249574T3 (es)
HK (1)	HK1066170A1 (es)
HR (1)	HRP20030624B1 (es)
HU (1)	HU229604B1 (es)
IL (2)	IL156872A0 (es)
JO (1)	JO2410B1 (es)
MA (1)	MA26993A1 (es)
MX (1)	MXPA03007166A (es)
MY (1)	MY131518A (es)
NO (1)	NO326133B1 (es)
NZ (1)	NZ526961A (es)
PA (1)	PA8539201A1 (es)
PE (1)	PE20020976A1 (es)
PL (1)	PL366918A1 (es)
RU (1)	RU2269527C2 (es)
SK (1)	SK11322003A3 (es)
WO (1)	WO2002064594A2 (es)
YU (1)	YU63703A (es)
ZA (1)	ZA200305938B (es)

Families Citing this family (40)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7053070B2 (en) *	2000-01-25	2006-05-30	Warner-Lambert Company	Pyrido[2,3-d]pyrimidine-2,7-diamine kinase inhibitors
ATE305303T1 (de)	2001-02-12	2005-10-15	Hoffmann La Roche	6-substituierte pyridopyrimidine
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US6696566B2 (en)	2004-02-24
HU229604B1 (en)	2014-02-28
RU2269527C2 (ru)	2006-02-10
HUP0303458A2 (hu)	2004-01-28
US7169794B2 (en)	2007-01-30
DK1361880T3 (da)	2006-01-23
EP1361880A2 (en)	2003-11-19
US20030171584A1 (en)	2003-09-11
NZ526961A (en)	2005-03-24
BR0207172A (pt)	2004-03-30
CA2434834C (en)	2010-09-14
HRP20030624B1 (en)	2007-03-31
US20070135458A1 (en)	2007-06-14
WO2002064594A2 (en)	2002-08-22
AU2002256615B2 (en)	2007-09-13
AR035854A1 (es)	2004-07-21
ATE305303T1 (de)	2005-10-15
IL156872A (en)	2009-07-20
NO20033540D0 (no)	2003-08-11
MY131518A (en)	2007-08-30
JP4064818B2 (ja)	2008-03-19
IL156872A0 (en)	2004-02-08
YU63703A (sh)	2006-05-25
CZ20032416A3 (cs)	2004-07-14
JP2004525896A (ja)	2004-08-26
CN1503672A (zh)	2004-06-09
DE60206363T2 (de)	2006-07-06
BRPI0207172B8 (pt)	2021-05-25
ZA200305938B (en)	2005-01-26
US7449581B2 (en)	2008-11-11
PL366918A1 (en)	2005-02-07
SK11322003A3 (en)	2004-10-05
ES2249574T3 (es)	2006-04-01
PA8539201A1 (es)	2004-08-31
DE60206363D1 (de)	2006-02-09
RU2003125887A (ru)	2005-03-20
HK1066170A1 (en)	2005-03-18
HUP0303458A3 (en)	2012-12-28
BRPI0207172B1 (pt)	2019-04-09
WO2002064594A3 (en)	2003-01-09
MA26993A1 (fr)	2004-12-20
PE20020976A1 (es)	2002-10-29
US20040116698A1 (en)	2004-06-17
CN100376571C (zh)	2008-03-26
NO20033540L (no)	2003-08-11
JO2410B1 (en)	2007-06-17
MXPA03007166A (es)	2003-11-18
HRP20030624A2 (en)	2005-06-30
KR100639772B1 (ko)	2006-10-30
KR20040018254A (ko)	2004-03-02
CA2434834A1 (en)	2002-08-22
EP1361880B1 (en)	2005-09-28

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Publication	Publication Date	Title
NO326133B1 (no)	2008-10-06	6-substituerte pyrido-pyrimidiner, fremgangsmate for fremstilling av slike, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom
EP1539755B1 (en)	2007-09-26	6-alkoxy-pyrido-pyrimidines as p-38 map kinase inhibitors
AU2001293784B2 (en)	2007-08-30	7-OXO pyridopyrimidines as inhibitors of a cellular proliferation
AU2002256615A1 (en)	2003-02-20	6-substituted pyrido-pyrimidines
AU2001293784A1 (en)	2002-06-06	7-OXO pyridopyrimidines as inhibitors of a cellular proliferation
EP1315727B1 (en)	2005-06-29	7-oxo pyridopyrimidines
AU2004289428B2 (en)	2010-06-03	Hydroxyalkyl substituted pyrido-7-pyrimidin-7-ones
US6506749B2 (en)	2003-01-14	7-oxo-pyridopyrimidines (I)
BG108085A (bg)	2004-12-30	6-заместени пиридо-пиримидини