NO310287B1 - <alfa>-substituerte pyrimidintioalkyl- og alkyleterforbindelser og farmasöytisk preparat inneholdende dissesom inhibitorer av viral reverstranskriptase - Google Patents
<alfa>-substituerte pyrimidintioalkyl- og alkyleterforbindelser og farmasöytisk preparat inneholdende dissesom inhibitorer av viral reverstranskriptase Download PDFInfo
- Publication number
- NO310287B1 NO310287B1 NO19975129A NO975129A NO310287B1 NO 310287 B1 NO310287 B1 NO 310287B1 NO 19975129 A NO19975129 A NO 19975129A NO 975129 A NO975129 A NO 975129A NO 310287 B1 NO310287 B1 NO 310287B1
- Authority
- NO
- Norway
- Prior art keywords
- chloro
- amino
- compound
- mmol
- thiopyrimidine
- Prior art date
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- -1 alkyl ether compounds Chemical class 0.000 title claims abstract description 99
- 239000000825 pharmaceutical preparation Substances 0.000 title claims 2
- 230000003612 virological effect Effects 0.000 title abstract description 9
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 472
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 162
- HBCQSNAFLVXVAY-UHFFFAOYSA-N pyrimidine-2-thiol Chemical compound SC1=NC=CC=N1 HBCQSNAFLVXVAY-UHFFFAOYSA-N 0.000 claims description 96
- 229910052757 nitrogen Inorganic materials 0.000 claims description 84
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 74
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 57
- 238000002360 preparation method Methods 0.000 claims description 54
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 50
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 48
- 229910052760 oxygen Inorganic materials 0.000 claims description 48
- 239000001301 oxygen Substances 0.000 claims description 48
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 35
- 229920006395 saturated elastomer Polymers 0.000 claims description 31
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 5
- 125000004534 benzothien-2-yl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 4
- MJDXSLDHQYJHAT-UHFFFAOYSA-N 5-bromo-6-chloro-2-(1-isoquinolin-3-ylethylsulfanyl)pyrimidin-4-amine Chemical compound C=1C2=CC=CC=C2C=NC=1C(C)SC1=NC(N)=C(Br)C(Cl)=N1 MJDXSLDHQYJHAT-UHFFFAOYSA-N 0.000 claims description 4
- DLUPKDAJXDJCTN-UHFFFAOYSA-N 6-chloro-2-(1-isoquinolin-3-ylethylsulfanyl)pyrimidin-4-amine Chemical compound C=1C2=CC=CC=C2C=NC=1C(C)SC1=NC(N)=CC(Cl)=N1 DLUPKDAJXDJCTN-UHFFFAOYSA-N 0.000 claims description 4
- 150000001204 N-oxides Chemical class 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 150000004677 hydrates Chemical class 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- OHJJJXKRCBKRQV-UHFFFAOYSA-N 2-(naphthalen-2-ylmethylsulfanyl)-6-(trifluoromethyl)pyrimidin-4-amine Chemical compound NC1=CC(C(F)(F)F)=NC(SCC=2C=C3C=CC=CC3=CC=2)=N1 OHJJJXKRCBKRQV-UHFFFAOYSA-N 0.000 claims description 3
- DYWKFGNOBPYHFY-UHFFFAOYSA-N 2-[(4-propan-2-ylpyridin-2-yl)methylsulfanyl]-6-(trifluoromethyl)pyrimidin-4-amine Chemical compound CC(C)C1=CC=NC(CSC=2N=C(C=C(N)N=2)C(F)(F)F)=C1 DYWKFGNOBPYHFY-UHFFFAOYSA-N 0.000 claims description 3
- NXHJCIKXCAANCH-UHFFFAOYSA-N 2-[(4-tert-butylpyridin-2-yl)methylsulfanyl]-6-(trifluoromethyl)pyrimidin-4-amine Chemical compound CC(C)(C)C1=CC=NC(CSC=2N=C(C=C(N)N=2)C(F)(F)F)=C1 NXHJCIKXCAANCH-UHFFFAOYSA-N 0.000 claims description 3
- JWSKWWBLADOQDM-UHFFFAOYSA-N 2-[1-(4-propan-2-ylpyridin-2-yl)ethylsulfanyl]-6-(trifluoromethyl)pyrimidin-4-amine Chemical compound CC(C)C1=CC=NC(C(C)SC=2N=C(C=C(N)N=2)C(F)(F)F)=C1 JWSKWWBLADOQDM-UHFFFAOYSA-N 0.000 claims description 3
- RYAYFARBZXVJPF-UHFFFAOYSA-N 6-amino-2-(naphthalen-2-ylmethylsulfanyl)pyrimidine-4-carbonitrile Chemical compound NC1=CC(C#N)=NC(SCC=2C=C3C=CC=CC3=CC=2)=N1 RYAYFARBZXVJPF-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- NRTBNQSBXMHVGW-ONEGZZNKSA-N (e)-4-(4-amino-6-chloropyrimidin-2-yl)sulfanyl-1-pyrrolidin-1-ylbut-2-en-1-one Chemical compound NC1=CC(Cl)=NC(SC\C=C\C(=O)N2CCCC2)=N1 NRTBNQSBXMHVGW-ONEGZZNKSA-N 0.000 claims description 2
- WSYFORMNOZEAEJ-AATRIKPKSA-N (e)-4-(4-amino-6-chloropyrimidin-2-yl)sulfanyl-n,n-diethylbut-2-enamide Chemical compound CCN(CC)C(=O)\C=C\CSC1=NC(N)=CC(Cl)=N1 WSYFORMNOZEAEJ-AATRIKPKSA-N 0.000 claims description 2
- PUIUVVGYMSCPOK-VOTSOKGWSA-N (e)-4-(4-amino-6-chloropyrimidin-2-yl)sulfanyl-n,n-diethylpent-2-enamide Chemical compound CCN(CC)C(=O)\C=C\C(C)SC1=NC(N)=CC(Cl)=N1 PUIUVVGYMSCPOK-VOTSOKGWSA-N 0.000 claims description 2
- SMEXPIBTHBJCLQ-SNAWJCMRSA-N (e)-4-(4-amino-6-chloropyrimidin-2-yl)sulfanyl-n-ethyl-n-methylbut-2-enamide Chemical compound CCN(C)C(=O)\C=C\CSC1=NC(N)=CC(Cl)=N1 SMEXPIBTHBJCLQ-SNAWJCMRSA-N 0.000 claims description 2
- MNFVXHMFVHIVHY-UHFFFAOYSA-N 2-(1-furo[2,3-c]pyridin-5-ylethylsulfanyl)-6-(trifluoromethyl)pyrimidin-4-amine Chemical compound C=1C=2C=COC=2C=NC=1C(C)SC1=NC(N)=CC(C(F)(F)F)=N1 MNFVXHMFVHIVHY-UHFFFAOYSA-N 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- PANGDCFLXUDHDI-UHFFFAOYSA-N 6,7-dihydro-5h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NCCC2=C1 PANGDCFLXUDHDI-UHFFFAOYSA-N 0.000 claims description 2
- WNPIEWUCGOSORI-UHFFFAOYSA-N 6-chloro-2-[1-(4-methylpyridin-2-yl)pentylsulfanyl]pyrimidin-4-amine Chemical compound C=1C(C)=CC=NC=1C(CCCC)SC1=NC(N)=CC(Cl)=N1 WNPIEWUCGOSORI-UHFFFAOYSA-N 0.000 claims description 2
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 2
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 150000005215 alkyl ethers Chemical class 0.000 abstract description 17
- 102100034343 Integrase Human genes 0.000 abstract description 9
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 abstract description 9
- 239000003112 inhibitor Substances 0.000 abstract description 5
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 514
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 411
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 395
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 225
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 203
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 200
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 198
- 239000011541 reaction mixture Substances 0.000 description 197
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 184
- 235000019439 ethyl acetate Nutrition 0.000 description 171
- 239000000741 silica gel Substances 0.000 description 170
- 229910002027 silica gel Inorganic materials 0.000 description 170
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 165
- 239000000243 solution Substances 0.000 description 151
- 239000000203 mixture Substances 0.000 description 147
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 145
- 238000004809 thin layer chromatography Methods 0.000 description 105
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 101
- 229910000027 potassium carbonate Inorganic materials 0.000 description 99
- 239000003921 oil Substances 0.000 description 92
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 90
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 87
- 238000005160 1H NMR spectroscopy Methods 0.000 description 83
- 239000007787 solid Substances 0.000 description 76
- 238000001819 mass spectrum Methods 0.000 description 74
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 63
- 239000013058 crude material Substances 0.000 description 60
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
- 238000000034 method Methods 0.000 description 55
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 54
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 54
- 238000004458 analytical method Methods 0.000 description 53
- 239000010410 layer Substances 0.000 description 52
- 229910000104 sodium hydride Inorganic materials 0.000 description 50
- 239000002480 mineral oil Substances 0.000 description 48
- 235000010446 mineral oil Nutrition 0.000 description 48
- 238000010992 reflux Methods 0.000 description 47
- FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 description 46
- 238000005481 NMR spectroscopy Methods 0.000 description 45
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 42
- 239000000706 filtrate Substances 0.000 description 40
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 37
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 37
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
- 239000012312 sodium hydride Substances 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 35
- 239000000284 extract Substances 0.000 description 33
- 125000001424 substituent group Chemical group 0.000 description 32
- OITKEKZIJXHOMS-UHFFFAOYSA-N 4-amino-6-chloro-1h-pyrimidine-2-thione;methanesulfonic acid Chemical compound CS(O)(=O)=O.NC1=CC(Cl)=NC(S)=N1 OITKEKZIJXHOMS-UHFFFAOYSA-N 0.000 description 29
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 27
- 208000030507 AIDS Diseases 0.000 description 26
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- NRGGMCIBEHEAIL-UHFFFAOYSA-N 2-ethylpyridine Chemical compound CCC1=CC=CC=N1 NRGGMCIBEHEAIL-UHFFFAOYSA-N 0.000 description 21
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 21
- 238000004587 chromatography analysis Methods 0.000 description 21
- 239000000463 material Substances 0.000 description 21
- 239000011734 sodium Substances 0.000 description 20
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 18
- 239000000725 suspension Substances 0.000 description 18
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 16
- 238000001816 cooling Methods 0.000 description 16
- 238000002425 crystallisation Methods 0.000 description 16
- 230000008025 crystallization Effects 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000005804 alkylation reaction Methods 0.000 description 15
- 239000004533 oil dispersion Substances 0.000 description 15
- 239000003039 volatile agent Substances 0.000 description 15
- 102000004190 Enzymes Human genes 0.000 description 14
- 108090000790 Enzymes Proteins 0.000 description 14
- 229940088598 enzyme Drugs 0.000 description 14
- 239000012065 filter cake Substances 0.000 description 14
- 239000006260 foam Substances 0.000 description 14
- 230000029936 alkylation Effects 0.000 description 13
- 239000012267 brine Substances 0.000 description 13
- 150000001721 carbon Chemical group 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- 239000011343 solid material Substances 0.000 description 12
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 11
- 241000725303 Human immunodeficiency virus Species 0.000 description 11
- 239000000908 ammonium hydroxide Substances 0.000 description 11
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 11
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 10
- FXUDMQXADIQKFJ-UHFFFAOYSA-N 4-amino-6-chloro-1h-pyrimidine-2-thione Chemical compound NC1=CC(Cl)=NC(S)=N1 FXUDMQXADIQKFJ-UHFFFAOYSA-N 0.000 description 10
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 10
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- UVGFRUBIRIRNOU-UHFFFAOYSA-N 2-chloro-6-(1-hydroxyethyl)-4-iodopyridin-3-ol Chemical compound CC(O)C1=CC(I)=C(O)C(Cl)=N1 UVGFRUBIRIRNOU-UHFFFAOYSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 229910001870 ammonium persulfate Inorganic materials 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 8
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 8
- UAKMHSRHDUBNJR-UHFFFAOYSA-N 4-methylpyridine-2-carbaldehyde Chemical compound CC1=CC=NC(C=O)=C1 UAKMHSRHDUBNJR-UHFFFAOYSA-N 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 150000004820 halides Chemical class 0.000 description 7
- 229910052740 iodine Inorganic materials 0.000 description 7
- 239000011630 iodine Substances 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 7
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 7
- XHHACLYUUYLTNG-UHFFFAOYSA-N 4-amino-6-(trifluoromethyl)-1h-pyrimidine-2-thione;methanesulfonic acid Chemical compound CS(O)(=O)=O.NC=1C=C(C(F)(F)F)NC(=S)N=1 XHHACLYUUYLTNG-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
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- BBMCPEOFGAIHQK-HWKANZROSA-N methyl (e)-4-bromo-3-methylbut-2-enoate Chemical compound COC(=O)\C=C(/C)CBr BBMCPEOFGAIHQK-HWKANZROSA-N 0.000 description 1
- RWIKCBHOVNDESJ-NSCUHMNNSA-N methyl (e)-4-bromobut-2-enoate Chemical compound COC(=O)\C=C\CBr RWIKCBHOVNDESJ-NSCUHMNNSA-N 0.000 description 1
- FNSGNNZYMUIWAD-HWKANZROSA-N methyl (e)-4-chloro-3-methylbut-2-enoate Chemical compound COC(=O)\C=C(/C)CCl FNSGNNZYMUIWAD-HWKANZROSA-N 0.000 description 1
- GTSWGSZEDFAGCU-HWKANZROSA-N methyl (e)-4-hydroxy-3-methylbut-2-enoate Chemical compound COC(=O)\C=C(/C)CO GTSWGSZEDFAGCU-HWKANZROSA-N 0.000 description 1
- HIPRDLZWAASLOU-SNAWJCMRSA-N methyl (e)-4-hydroxy-3-methylpent-2-enoate Chemical compound COC(=O)\C=C(/C)C(C)O HIPRDLZWAASLOU-SNAWJCMRSA-N 0.000 description 1
- WDMAQUDAWOUDAW-UHFFFAOYSA-N methyl 2-(4-amino-6-chloropyrimidin-2-yl)sulfanyl-2-(4-methylpyridin-2-yl)acetate Chemical compound C=1C(C)=CC=NC=1C(C(=O)OC)SC1=NC(N)=CC(Cl)=N1 WDMAQUDAWOUDAW-UHFFFAOYSA-N 0.000 description 1
- NFIVBZOMIAKBLL-UHFFFAOYSA-N methyl 3-[(4-amino-6-chloropyrimidin-2-yl)sulfanylmethyl]benzoate Chemical compound COC(=O)C1=CC=CC(CSC=2N=C(Cl)C=C(N)N=2)=C1 NFIVBZOMIAKBLL-UHFFFAOYSA-N 0.000 description 1
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- SNVLJLYUUXKWOJ-UHFFFAOYSA-N methylidenecarbene Chemical compound C=[C] SNVLJLYUUXKWOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000001878 mycolytic effect Effects 0.000 description 1
- FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 1
- QYZFTMMPKCOTAN-UHFFFAOYSA-N n-[2-(2-hydroxyethylamino)ethyl]-2-[[1-[2-(2-hydroxyethylamino)ethylamino]-2-methyl-1-oxopropan-2-yl]diazenyl]-2-methylpropanamide Chemical compound OCCNCCNC(=O)C(C)(C)N=NC(C)(C)C(=O)NCCNCCO QYZFTMMPKCOTAN-UHFFFAOYSA-N 0.000 description 1
- NNKPHNTWNILINE-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxopyrazin-1-yl]benzamide Chemical compound CNCCOC1=CC=CC=C1C1(NC=2C(N(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=CN=2)=O)CC1 NNKPHNTWNILINE-UHFFFAOYSA-N 0.000 description 1
- IOXXVNYDGIXMIP-UHFFFAOYSA-N n-methylprop-2-en-1-amine Chemical compound CNCC=C IOXXVNYDGIXMIP-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- LCCNCVORNKJIRZ-UHFFFAOYSA-N parathion Chemical compound CCOP(=S)(OCC)OC1=CC=C([N+]([O-])=O)C=C1 LCCNCVORNKJIRZ-UHFFFAOYSA-N 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 102200009479 rs141772938 Human genes 0.000 description 1
- 102200131341 rs267607614 Human genes 0.000 description 1
- 102200069353 rs8103142 Human genes 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- MZIYQMVHASXABC-UHFFFAOYSA-N tetrakis(ethenyl)stannane Chemical compound C=C[Sn](C=C)(C=C)C=C MZIYQMVHASXABC-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- ZEMGGZBWXRYJHK-UHFFFAOYSA-N thiouracil Chemical class O=C1C=CNC(=S)N1 ZEMGGZBWXRYJHK-UHFFFAOYSA-N 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 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
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- ULYLMHUHFUQKOE-UHFFFAOYSA-N trimethyl(prop-2-ynyl)silane Chemical compound C[Si](C)(C)CC#C ULYLMHUHFUQKOE-UHFFFAOYSA-N 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/38—One sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/56—One oxygen atom and one sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/60—Three or more oxygen or sulfur atoms
-
- 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
- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US43670895A | 1995-05-08 | 1995-05-08 | |
PCT/US1996/006119 WO1996035678A1 (en) | 1995-05-08 | 1996-05-03 | Alpha-substituted pyrimidine-thioalkyl and alkylether compounds as inhibitors of viral reverse transcriptase |
Publications (3)
Publication Number | Publication Date |
---|---|
NO975129D0 NO975129D0 (no) | 1997-11-07 |
NO975129L NO975129L (no) | 1998-01-07 |
NO310287B1 true NO310287B1 (no) | 2001-06-18 |
Family
ID=23733510
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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NO19975129A NO310287B1 (no) | 1995-05-08 | 1997-11-07 | <alfa>-substituerte pyrimidintioalkyl- og alkyleterforbindelser og farmasöytisk preparat inneholdende dissesom inhibitorer av viral reverstranskriptase |
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US (1) | US6043248A (ru) |
EP (2) | EP0824524B1 (ru) |
JP (1) | JPH11507017A (ru) |
KR (1) | KR100445498B1 (ru) |
CN (2) | CN1535958A (ru) |
AT (1) | ATE275550T1 (ru) |
AU (1) | AU712404B2 (ru) |
BR (1) | BR9608265A (ru) |
CA (1) | CA2216099C (ru) |
CZ (1) | CZ293135B6 (ru) |
DE (1) | DE69633332T2 (ru) |
ES (1) | ES2227586T3 (ru) |
GE (1) | GEP20002297B (ru) |
HK (1) | HK1009446A1 (ru) |
HU (1) | HUP9801995A3 (ru) |
IL (1) | IL118075A0 (ru) |
MX (1) | MX9708582A (ru) |
NO (1) | NO310287B1 (ru) |
NZ (1) | NZ307089A (ru) |
PL (1) | PL323240A1 (ru) |
PT (1) | PT824524E (ru) |
RU (1) | RU2167155C2 (ru) |
SK (1) | SK150297A3 (ru) |
TW (1) | TW450962B (ru) |
UA (1) | UA56992C2 (ru) |
WO (1) | WO1996035678A1 (ru) |
ZA (1) | ZA963281B (ru) |
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
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US6124306A (en) * | 1997-09-25 | 2000-09-26 | Pharmacia & Upjohn Company | Thioalkyl alpha substituted pyrimidine compounds |
US6111111A (en) * | 1997-10-23 | 2000-08-29 | Kuraray Co., Ltd. | Intermediates for producing pyridine derivatives |
WO2000015229A1 (en) | 1998-09-17 | 2000-03-23 | Bristol-Myers Squibb Company | METHOD FOR TREATING DIABETES EMPLOYING AN aP2 INHIBITOR AND COMBINATION |
US7358254B2 (en) | 2001-07-13 | 2008-04-15 | Bristol-Myers Squibb Company | Method for treating atherosclerosis employing an aP2 inhibitor and combination |
CA2376951A1 (en) | 1999-06-30 | 2001-01-04 | Peter J. Sinclair | Src kinase inhibitor compounds |
JP2003523942A (ja) | 1999-06-30 | 2003-08-12 | メルク エンド カムパニー インコーポレーテッド | Srcキナーゼ阻害剤化合物 |
JP2003503351A (ja) | 1999-06-30 | 2003-01-28 | メルク エンド カムパニー インコーポレーテッド | Srcキナーゼ阻害化合物 |
US7138404B2 (en) * | 2001-05-23 | 2006-11-21 | Hoffmann-La Roche Inc. | 4-aminopyrimidine derivatives |
US7923056B2 (en) | 2007-06-01 | 2011-04-12 | Illinois Tool Works Inc. | Method and apparatus for dispensing material on a substrate |
CA2762680C (en) | 2009-05-21 | 2018-04-17 | Chlorion Pharma, Inc. | Methyl sulfanyl pyrmidmes useful as antiinflammatories, analgesics, and antiepileptics |
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- 1996-05-03 DE DE69633332T patent/DE69633332T2/de not_active Expired - Fee Related
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- 1996-05-03 JP JP8534120A patent/JPH11507017A/ja not_active Withdrawn
- 1996-05-03 BR BR9608265A patent/BR9608265A/pt not_active Application Discontinuation
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- 1996-05-03 CN CNA200410032589XA patent/CN1535958A/zh active Pending
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1997
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