KR100639772B1 - 6-치환된 피리도-피리미딘 - Google Patents
6-치환된 피리도-피리미딘 Download PDFInfo
- Publication number
- KR100639772B1 KR100639772B1 KR1020037010562A KR20037010562A KR100639772B1 KR 100639772 B1 KR100639772 B1 KR 100639772B1 KR 1020037010562 A KR1020037010562 A KR 1020037010562A KR 20037010562 A KR20037010562 A KR 20037010562A KR 100639772 B1 KR100639772 B1 KR 100639772B1
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- cycloalkyl
- hydrogen
- amino
- heteroalkyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
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- -1 6-substituted pyrido-pyrimidine Chemical class 0.000 title claims description 412
- 150000001875 compounds Chemical class 0.000 claims abstract description 202
- 238000000034 method Methods 0.000 claims abstract description 85
- 125000000217 alkyl group Chemical group 0.000 claims description 281
- 229910052739 hydrogen Inorganic materials 0.000 claims description 164
- 239000001257 hydrogen Substances 0.000 claims description 164
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 148
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 124
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 110
- 150000002431 hydrogen Chemical class 0.000 claims description 103
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 99
- 125000003118 aryl group Chemical group 0.000 claims description 91
- 150000001412 amines Chemical class 0.000 claims description 78
- 125000003545 alkoxy group Chemical group 0.000 claims description 72
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 61
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 57
- 125000001188 haloalkyl group Chemical group 0.000 claims description 54
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 53
- 125000000623 heterocyclic group Chemical group 0.000 claims description 52
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 49
- 125000002252 acyl group Chemical group 0.000 claims description 44
- 238000004519 manufacturing process Methods 0.000 claims description 41
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 39
- 125000001072 heteroaryl group Chemical group 0.000 claims description 39
- 150000003839 salts Chemical class 0.000 claims description 38
- 201000010099 disease Diseases 0.000 claims description 37
- 125000001424 substituent group Chemical group 0.000 claims description 34
- 229920006395 saturated elastomer Polymers 0.000 claims description 31
- 125000005843 halogen group Chemical group 0.000 claims description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 30
- 125000004432 carbon atom Chemical group C* 0.000 claims description 27
- 229910052717 sulfur Inorganic materials 0.000 claims description 27
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 23
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 21
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 21
- 125000002947 alkylene group Chemical group 0.000 claims description 20
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 19
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 18
- 125000006413 ring segment Chemical group 0.000 claims description 17
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 16
- 125000004104 aryloxy group Chemical group 0.000 claims description 16
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 15
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 15
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 12
- 239000004215 Carbon black (E152) Substances 0.000 claims description 12
- 229930195733 hydrocarbon Natural products 0.000 claims description 12
- MNLAVFKVRUQAKW-UHFFFAOYSA-N VR nerve agent Chemical compound CCN(CC)CCSP(C)(=O)OCC(C)C MNLAVFKVRUQAKW-UHFFFAOYSA-N 0.000 claims description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 125000001769 aryl amino group Chemical group 0.000 claims description 10
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 125000002950 monocyclic group Chemical group 0.000 claims description 10
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000004442 acylamino group Chemical group 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 8
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 8
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 7
- 230000001590 oxidative effect Effects 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 6
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 5
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 5
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 5
- 206010003246 arthritis Diseases 0.000 claims description 5
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 229910052707 ruthenium Inorganic materials 0.000 claims description 3
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims description 2
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 claims description 2
- CVJYZPWMZPFOBW-UHFFFAOYSA-N 6-(2,4-difluorophenoxy)-2-(oxan-4-ylamino)-8-propylpyrido[2,3-d]pyrimidin-7-one Chemical compound N=1C=C2C=C(OC=3C(=CC(F)=CC=3)F)C(=O)N(CCC)C2=NC=1NC1CCOCC1 CVJYZPWMZPFOBW-UHFFFAOYSA-N 0.000 claims 2
- CQBKXXDWVJIDMM-UHFFFAOYSA-N 6-(2,4-difluorophenoxy)-2-[(4-hydroxy-4-methylpentan-2-yl)amino]-8-methylpyrido[2,3-d]pyrimidin-7-one Chemical compound O=C1N(C)C2=NC(NC(CC(C)(C)O)C)=NC=C2C=C1OC1=CC=C(F)C=C1F CQBKXXDWVJIDMM-UHFFFAOYSA-N 0.000 claims 2
- KKKRKRMVJRHDMG-UHFFFAOYSA-N 6-(2,4-difluorophenoxy)-8-methyl-2-(oxan-4-ylamino)pyrido[2,3-d]pyrimidin-7-one Chemical compound N=1C=C2C=C(OC=3C(=CC(F)=CC=3)F)C(=O)N(C)C2=NC=1NC1CCOCC1 KKKRKRMVJRHDMG-UHFFFAOYSA-N 0.000 claims 2
- BJYSBGCEJCKTCI-UHFFFAOYSA-N 8-cyclopropyl-6-(2,4-difluorophenoxy)-2-(oxan-4-ylamino)pyrido[2,3-d]pyrimidin-7-one Chemical compound FC1=CC(F)=CC=C1OC(C(N(C1CC1)C1=N2)=O)=CC1=CN=C2NC1CCOCC1 BJYSBGCEJCKTCI-UHFFFAOYSA-N 0.000 claims 2
- 238000002360 preparation method Methods 0.000 abstract description 162
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 abstract description 19
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 abstract description 19
- 230000001404 mediated effect Effects 0.000 abstract description 12
- 239000000543 intermediate Substances 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 360
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 311
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 216
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 203
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 152
- 239000000243 solution Substances 0.000 description 143
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 142
- 239000000203 mixture Substances 0.000 description 129
- 150000003254 radicals Chemical class 0.000 description 129
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 123
- 235000019439 ethyl acetate Nutrition 0.000 description 113
- 238000001819 mass spectrum Methods 0.000 description 111
- 150000003457 sulfones Chemical class 0.000 description 107
- 239000007787 solid Substances 0.000 description 105
- 239000011541 reaction mixture Substances 0.000 description 92
- 239000000047 product Substances 0.000 description 78
- 238000006243 chemical reaction Methods 0.000 description 77
- 238000002844 melting Methods 0.000 description 70
- 230000008018 melting Effects 0.000 description 70
- 239000002904 solvent Substances 0.000 description 68
- 230000002829 reductive effect Effects 0.000 description 65
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 62
- 239000012267 brine Substances 0.000 description 61
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 59
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 50
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 50
- 238000001914 filtration Methods 0.000 description 49
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
- 239000002244 precipitate Substances 0.000 description 47
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 39
- 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 38
- 229910004298 SiO 2 Inorganic materials 0.000 description 33
- 238000003756 stirring Methods 0.000 description 33
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
- 238000004440 column chromatography Methods 0.000 description 32
- 238000001704 evaporation Methods 0.000 description 32
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 31
- 230000008020 evaporation Effects 0.000 description 30
- 239000000725 suspension Substances 0.000 description 30
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- WRWYGOVGIGCDLE-UHFFFAOYSA-N [O]c1ccccc1F Chemical group [O]c1ccccc1F WRWYGOVGIGCDLE-UHFFFAOYSA-N 0.000 description 27
- NLALOHVNOVPDGN-UHFFFAOYSA-N 3,3-diethoxy-2-formylpropanenitrile;potassium Chemical compound [K].CCOC(OCC)C(C=O)C#N NLALOHVNOVPDGN-UHFFFAOYSA-N 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 25
- 229910000027 potassium carbonate Inorganic materials 0.000 description 25
- 235000011181 potassium carbonates Nutrition 0.000 description 25
- 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
- 239000010410 layer Substances 0.000 description 22
- 239000012043 crude product Substances 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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 16
- 238000001035 drying Methods 0.000 description 16
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
- 235000019341 magnesium sulphate Nutrition 0.000 description 16
- 239000011734 sodium Substances 0.000 description 16
- 235000017557 sodium bicarbonate Nutrition 0.000 description 16
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 235000010265 sodium sulphite Nutrition 0.000 description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 11
- 102100040247 Tumor necrosis factor Human genes 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- 238000012746 preparative thin layer chromatography Methods 0.000 description 11
- 238000004809 thin layer chromatography Methods 0.000 description 11
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-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
- AHVQYHFYQWKUKB-UHFFFAOYSA-N oxan-4-amine Chemical compound NC1CCOCC1 AHVQYHFYQWKUKB-UHFFFAOYSA-N 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 8
- 102000004127 Cytokines Human genes 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 8
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 150000003462 sulfoxides Chemical class 0.000 description 8
- 108010002352 Interleukin-1 Proteins 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 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
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 239000003039 volatile agent Substances 0.000 description 7
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- 239000000825 pharmaceutical preparation Substances 0.000 description 6
- 239000000651 prodrug Substances 0.000 description 6
- 229940002612 prodrug Drugs 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 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 5
- 241000124008 Mammalia Species 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 5
- 150000001299 aldehydes Chemical group 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 125000001544 thienyl group Chemical group 0.000 description 5
- PDNZJLMPXLQDPL-UHFFFAOYSA-N (1-aminocyclopentyl)methanol Chemical compound OCC1(N)CCCC1 PDNZJLMPXLQDPL-UHFFFAOYSA-N 0.000 description 4
- YURXCUVDCIDDHM-WCCKRBBISA-N (3s)-3-amino-2-methylbutan-2-ol;hydrochloride Chemical compound Cl.C[C@H](N)C(C)(C)O YURXCUVDCIDDHM-WCCKRBBISA-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
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 4
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-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
- 208000030507 AIDS Diseases 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-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
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- 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
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- 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
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- 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]
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- 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
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- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Physical Education & Sports Medicine (AREA)
- Heart & Thoracic Surgery (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)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US26837501P | 2001-02-12 | 2001-02-12 | |
| US60/268,375 | 2001-02-12 | ||
| US33465401P | 2001-11-30 | 2001-11-30 | |
| US60/334,654 | 2001-11-30 | ||
| PCT/EP2002/001106 WO2002064594A2 (en) | 2001-02-12 | 2002-02-04 | 6-substituted pyrido-pyrimidines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20040018254A KR20040018254A (ko) | 2004-03-02 |
| KR100639772B1 true KR100639772B1 (ko) | 2006-10-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020037010562A Expired - Lifetime KR100639772B1 (ko) | 2001-02-12 | 2002-02-04 | 6-치환된 피리도-피리미딘 |
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| JP (1) | JP4064818B2 (https=) |
| KR (1) | KR100639772B1 (https=) |
| CN (1) | CN100376571C (https=) |
| AR (1) | AR035854A1 (https=) |
| AT (1) | ATE305303T1 (https=) |
| AU (1) | AU2002256615B2 (https=) |
| BR (1) | BRPI0207172B8 (https=) |
| CA (1) | CA2434834C (https=) |
| CZ (1) | CZ20032416A3 (https=) |
| DE (1) | DE60206363T2 (https=) |
| DK (1) | DK1361880T3 (https=) |
| ES (1) | ES2249574T3 (https=) |
| HR (1) | HRP20030624B1 (https=) |
| HU (1) | HU229604B1 (https=) |
| IL (2) | IL156872A0 (https=) |
| JO (1) | JO2410B1 (https=) |
| MA (1) | MA26993A1 (https=) |
| MX (1) | MXPA03007166A (https=) |
| MY (1) | MY131518A (https=) |
| NO (1) | NO326133B1 (https=) |
| NZ (1) | NZ526961A (https=) |
| PA (1) | PA8539201A1 (https=) |
| PE (1) | PE20020976A1 (https=) |
| PL (1) | PL366918A1 (https=) |
| RU (1) | RU2269527C2 (https=) |
| SK (1) | SK11322003A3 (https=) |
| WO (1) | WO2002064594A2 (https=) |
| YU (1) | YU63703A (https=) |
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Families Citing this family (42)
| 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 |
| DE60206363T2 (de) | 2001-02-12 | 2006-07-06 | F. Hoffmann-La Roche Ag | 6-substituierte pyridopyrimidine |
| ES2251677T3 (es) * | 2002-01-22 | 2006-05-01 | Warner-Lambert Company Llc | 2-(piridin-2-ilamino)-pirido(2,3-d)pirimidin-7-onas. |
| EP1492790A1 (en) | 2002-04-03 | 2005-01-05 | F. Hoffmann-La Roche Ag | Imidazo fused compounds |
| CA2492112A1 (en) * | 2002-08-06 | 2004-02-19 | F. Hoffmann-La Roche Ag | 6-alkoxy-pyrido-pyrimidines as p-38 map kinase inhibitors |
| EP2181704B1 (en) | 2002-12-30 | 2015-05-06 | Angiotech International Ag | Drug delivery from rapid gelling polymer composition |
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