SK8152001A3 - Il-5 inhibiting 6-azauracil derivatives - Google Patents
Il-5 inhibiting 6-azauracil derivatives Download PDFInfo
- Publication number
- SK8152001A3 SK8152001A3 SK815-2001A SK8152001A SK8152001A3 SK 8152001 A3 SK8152001 A3 SK 8152001A3 SK 8152001 A SK8152001 A SK 8152001A SK 8152001 A3 SK8152001 A3 SK 8152001A3
- Authority
- SK
- Slovakia
- Prior art keywords
- alkyl
- het
- formula
- optionally substituted
- thiazolyl
- Prior art date
Links
- SSPYSWLZOPCOLO-UHFFFAOYSA-N 6-azauracil Chemical class O=C1C=NNC(=O)N1 SSPYSWLZOPCOLO-UHFFFAOYSA-N 0.000 title claims description 6
- 230000002401 inhibitory effect Effects 0.000 title description 2
- 101150015560 IL5 gene Proteins 0.000 title 1
- -1 C1-6alkylO Chemical group 0.000 claims abstract description 186
- 150000001875 compounds Chemical class 0.000 claims abstract description 174
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 53
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 49
- 125000003118 aryl group Chemical group 0.000 claims abstract description 49
- 239000000203 mixture Substances 0.000 claims abstract description 46
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 33
- 238000000034 method Methods 0.000 claims abstract description 32
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 24
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 24
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims abstract description 21
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 18
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 12
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 7
- 230000008569 process Effects 0.000 claims abstract description 7
- 125000003277 amino group Chemical group 0.000 claims abstract description 5
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 314
- 125000000335 thiazolyl group Chemical group 0.000 claims description 88
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 83
- 125000001424 substituent group Chemical group 0.000 claims description 64
- 239000002904 solvent Substances 0.000 claims description 49
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 239000001257 hydrogen Substances 0.000 claims description 46
- 125000003545 alkoxy group Chemical group 0.000 claims description 42
- 238000006243 chemical reaction Methods 0.000 claims description 39
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 34
- 150000002431 hydrogen Chemical class 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 150000002367 halogens Chemical class 0.000 claims description 30
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 27
- 125000003386 piperidinyl group Chemical group 0.000 claims description 25
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 22
- 239000012442 inert solvent Substances 0.000 claims description 22
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 22
- 239000002585 base Substances 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 125000001544 thienyl group Chemical group 0.000 claims description 19
- 125000002541 furyl group Chemical group 0.000 claims description 18
- 125000002883 imidazolyl group Chemical group 0.000 claims description 18
- DXBWJLDFSICTIH-UHFFFAOYSA-N pyrazine-2-carbaldehyde Chemical compound O=CC1=CN=CC=N1 DXBWJLDFSICTIH-UHFFFAOYSA-N 0.000 claims description 18
- 125000001425 triazolyl group Chemical group 0.000 claims description 17
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 16
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 16
- 125000002971 oxazolyl group Chemical group 0.000 claims description 16
- 125000004193 piperazinyl group Chemical group 0.000 claims description 16
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 15
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 15
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 14
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 14
- 125000002757 morpholinyl group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 125000004682 aminothiocarbonyl group Chemical group NC(=S)* 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 11
- 125000004306 triazinyl group Chemical group 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 10
- 125000004104 aryloxy group Chemical group 0.000 claims description 10
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
- 125000005879 dioxolanyl group Chemical group 0.000 claims description 10
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 10
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 10
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 10
- 125000002755 pyrazolinyl group Chemical group 0.000 claims description 10
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 10
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 10
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 10
- 125000001166 thiolanyl group Chemical group 0.000 claims description 10
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 9
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 125000000532 dioxanyl group Chemical group 0.000 claims description 9
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 claims description 9
- 150000002576 ketones Chemical class 0.000 claims description 9
- 125000005968 oxazolinyl group Chemical group 0.000 claims description 9
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 8
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 8
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 208000006673 asthma Diseases 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 7
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 7
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 7
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 7
- 230000009466 transformation Effects 0.000 claims description 7
- 125000005947 C1-C6 alkylsulfonyloxy group Chemical group 0.000 claims description 6
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 6
- 125000005110 aryl thio group Chemical group 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000005990 isobenzothienyl group Chemical group 0.000 claims description 6
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000005493 quinolyl group Chemical group 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 5
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 5
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 5
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 4
- 125000002393 azetidinyl group Chemical group 0.000 claims description 4
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 4
- 239000012620 biological material Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 238000003384 imaging method Methods 0.000 claims description 4
- 231100000252 nontoxic Toxicity 0.000 claims description 4
- 230000003000 nontoxic effect Effects 0.000 claims description 4
- 210000000056 organ Anatomy 0.000 claims description 4
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 4
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 4
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 238000002372 labelling Methods 0.000 claims description 3
- 238000000163 radioactive labelling Methods 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 2
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 2
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 238000007363 ring formation reaction Methods 0.000 claims description 2
- BFGQTWYXWNCTSX-UHFFFAOYSA-N triazine-4,5-dione Chemical compound O=C1C=NN=NC1=O BFGQTWYXWNCTSX-UHFFFAOYSA-N 0.000 claims description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims 5
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- 239000003513 alkali Substances 0.000 claims 1
- 239000004927 clay Substances 0.000 claims 1
- 125000005883 dithianyl group Chemical group 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 150000003527 tetrahydropyrans Chemical class 0.000 claims 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims 1
- 238000000844 transformation Methods 0.000 claims 1
- 125000005455 trithianyl group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 5
- 125000001475 halogen functional group Chemical group 0.000 abstract 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 abstract 2
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 abstract 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 97
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- 239000000460 chlorine Substances 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- 239000000243 solution Substances 0.000 description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 210000003979 eosinophil Anatomy 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- 239000003480 eluent Substances 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 150000003254 radicals Chemical class 0.000 description 10
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 9
- 108010002616 Interleukin-5 Proteins 0.000 description 9
- 102100039897 Interleukin-5 Human genes 0.000 description 8
- 230000002327 eosinophilic effect Effects 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 229920000858 Cyclodextrin Polymers 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- 208000027866 inflammatory disease Diseases 0.000 description 7
- 229940100602 interleukin-5 Drugs 0.000 description 7
- 230000002285 radioactive effect Effects 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 206010039085 Rhinitis allergic Diseases 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 201000010105 allergic rhinitis Diseases 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 230000001419 dependent effect Effects 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- 230000022023 interleukin-5 production Effects 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 206010012438 Dermatitis atopic Diseases 0.000 description 5
- 201000008937 atopic dermatitis Diseases 0.000 description 5
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 238000004811 liquid chromatography Methods 0.000 description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102000019034 Chemokines Human genes 0.000 description 4
- 108010012236 Chemokines Proteins 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical group 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
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- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 3
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- 229910052744 lithium Inorganic materials 0.000 description 1
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- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- 239000000463 material Substances 0.000 description 1
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- 239000002184 metal Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
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- 210000001616 monocyte Anatomy 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
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- 125000001196 nonadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical group OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
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- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 description 1
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- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 230000000451 tissue damage Effects 0.000 description 1
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- 238000011200 topical administration Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- PRXNKYBFWAWBNZ-UHFFFAOYSA-N trimethylphenylammonium tribromide Chemical compound Br[Br-]Br.C[N+](C)(C)C1=CC=CC=C1 PRXNKYBFWAWBNZ-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
- C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
- C07D253/06—1,2,4-Triazines
- C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
- C07D253/07—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members with hetero atoms, or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D253/075—Two hetero atoms, in positions 3 and 5
-
- 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
- A61P11/06—Antiasthmatics
-
- 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
- A61P37/08—Antiallergic agents
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP98204336 | 1998-12-18 | ||
| PCT/EP1999/010169 WO2000037451A1 (en) | 1998-12-18 | 1999-12-16 | Il-5 inhibiting 6-azauracil derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK8152001A3 true SK8152001A3 (en) | 2002-04-04 |
Family
ID=8234494
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK815-2001A SK8152001A3 (en) | 1998-12-18 | 1999-12-16 | Il-5 inhibiting 6-azauracil derivatives |
Country Status (35)
| Country | Link |
|---|---|
| US (1) | US6803364B1 (pl) |
| EP (1) | EP1140873B1 (pl) |
| JP (1) | JP2002533331A (pl) |
| KR (1) | KR100635721B1 (pl) |
| CN (1) | CN100343239C (pl) |
| AR (1) | AR021887A1 (pl) |
| AT (1) | ATE365723T1 (pl) |
| AU (1) | AU773780B2 (pl) |
| BG (1) | BG105602A (pl) |
| BR (1) | BR9916366A (pl) |
| CA (1) | CA2354511A1 (pl) |
| CO (1) | CO5150147A1 (pl) |
| CZ (1) | CZ20012062A3 (pl) |
| DE (1) | DE69936396T2 (pl) |
| DK (1) | DK1140873T3 (pl) |
| EA (1) | EA004806B1 (pl) |
| EE (1) | EE200100320A (pl) |
| ES (1) | ES2289835T3 (pl) |
| HK (1) | HK1042491A1 (pl) |
| HR (1) | HRP20010455A2 (pl) |
| HU (1) | HUP0104641A3 (pl) |
| ID (1) | ID28880A (pl) |
| IL (1) | IL143766A (pl) |
| MY (1) | MY125808A (pl) |
| NO (1) | NO319814B1 (pl) |
| NZ (1) | NZ512748A (pl) |
| PL (1) | PL198205B1 (pl) |
| PT (1) | PT1140873E (pl) |
| SA (1) | SA00201030B1 (pl) |
| SK (1) | SK8152001A3 (pl) |
| TR (1) | TR200101729T2 (pl) |
| TW (1) | TWI249530B (pl) |
| UA (1) | UA73107C2 (pl) |
| WO (1) | WO2000037451A1 (pl) |
| ZA (1) | ZA200104942B (pl) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8466096B2 (en) * | 2007-04-26 | 2013-06-18 | Afton Chemical Corporation | 1,3,2-dioxaphosphorinane, 2-sulfide derivatives for use as anti-wear additives in lubricant compositions |
| RU2523651C2 (ru) * | 2012-05-22 | 2014-07-20 | Государственное бюджетное образовательное учреждение высшего профессионального образования "Владивостокский государственный медицинский университет" Министерства здравоохранения и социального развития Российской Федерации (ГБОУ ВПО ВГМУ Минздравсоцразвития России) | Способ дифференцированного контроля базисного противовоспалительного лечения бронхиальной астмы у детей и подростков |
| RU2506045C1 (ru) * | 2012-09-05 | 2014-02-10 | Федеральное государственное бюджетное учреждение "Дальневосточный научный центр физиологии и патологии дыхания" Сибирского отделения РАМН | Способ прогнозирования достижения контроля бронхиальной астмы |
| CN119161311B (zh) * | 2024-11-20 | 2025-02-11 | 北京纳百生物科技有限公司 | 一种地克珠利抗原及其合成方法和应用 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2149645A1 (de) | 1970-10-07 | 1972-09-14 | Pfizer | 2-Phenyl-as-triazin-3.5-(2H,4H)-dione und die Verwendung dieser Verbindungen zur Bekaempfung der Coccidiose |
| US3912723A (en) | 1971-03-29 | 1975-10-14 | Pfizer | 2-Phenyl-as-triazine-3,5(2H,4H)diones |
| US3883528A (en) | 1974-04-19 | 1975-05-13 | Pfizer | Preparation of 2(aryl)-as-triazine-3,5(2H,4H)-dione coccidiostats |
| CA1244024A (en) | 1984-08-01 | 1988-11-01 | Gustaaf M. Boeckx | .alpha.- ARYL-4-(4,5-DIHYDRO-3,5-DIOXO-1,2,4-TRIAZIN- 2(3H)-YL)BENZENEACETONITRILES |
| US4631278A (en) | 1984-08-01 | 1986-12-23 | Janssen Pharmaceutica N.V. | Anti-protozoal α-aryl-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)-benzeneacetonitrile derivatives, pharmaceutical compositions, and method of use therefor |
| GB8602342D0 (en) * | 1986-01-30 | 1986-03-05 | Janssen Pharmaceutica Nv | 5 6-dihydro-2-(substituted phenyl)-1 2 4-triazine-3 5(2h 4h)-diones |
| CA1331757C (en) | 1988-02-29 | 1994-08-30 | Janssen Pharmaceutica Naamloze Vennootschap | 5-lipoxygenase inhibiting 4-(4-phenyl-1-piperazinyl)phenols |
| DE4120138A1 (de) | 1991-06-19 | 1992-12-24 | Bayer Ag | Substituierte hexahydro-1,2,4-triazindione, verfahren zu ihrer herstellung, zwischenprodukte dafuer und ihre verwendung |
| EP0476439A1 (de) | 1990-09-18 | 1992-03-25 | Bayer Ag | Substituierte 1,2,4-Triazindione, Verfahren zu ihrer Herstellung, Zwischenprodukte dafür und ihre Verwendung |
| TW263495B (pl) | 1992-12-23 | 1995-11-21 | Celltech Ltd | |
| GB9304920D0 (en) | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| TW403741B (en) | 1993-10-15 | 2000-09-01 | Takeda Chemical Industries Ltd | Triazine derivative, production and use thereof |
| TW332201B (en) | 1995-04-06 | 1998-05-21 | Janssen Pharmaceutica Nv | 1,3-Dihydro-1-(phenylalkyl)-2H-imidazol-2-one derivatives |
| DE69615601T2 (de) | 1995-04-14 | 2002-07-11 | Takeda Schering-Plough Animal Health K.K., Osaka | Verfahren zur Herstellung von Triazinderivate |
| CA2214256A1 (en) * | 1996-08-30 | 1998-02-28 | Takeda Chemical Industries, Ltd. | 1,2,4-triazine-3,5-dione derivatives, their production and use thereof |
| BR9811499A (pt) * | 1997-07-10 | 2000-09-19 | Janssen Pharmaceutica Nv | "derivados da 6-azauracila como inibidores da il-5" |
| PL337947A1 (en) * | 1997-07-10 | 2000-09-11 | Janssen Pharmaceutica Nv | Il-5 inhibiting derivatives of 6-azauracil |
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1999
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