HUE033476T2 - RSV vírus elleni vegyületek - Google Patents
RSV vírus elleni vegyületek Download PDFInfo
- Publication number
- HUE033476T2 HUE033476T2 HUE13779195A HUE13779195A HUE033476T2 HU E033476 T2 HUE033476 T2 HU E033476T2 HU E13779195 A HUE13779195 A HU E13779195A HU E13779195 A HUE13779195 A HU E13779195A HU E033476 T2 HUE033476 T2 HU E033476T2
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- HU
- Hungary
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- halogen
- alkyl
- formula
- mmol
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- 150000001875 compounds Chemical class 0.000 title claims description 203
- 230000000840 anti-viral effect Effects 0.000 title description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 93
- 150000002367 halogens Chemical class 0.000 claims description 92
- 229910052739 hydrogen Inorganic materials 0.000 claims description 79
- 125000003118 aryl group Chemical group 0.000 claims description 55
- 125000001072 heteroaryl group Chemical group 0.000 claims description 54
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 51
- 239000001257 hydrogen Substances 0.000 claims description 47
- 238000000034 method Methods 0.000 claims description 47
- 229910052799 carbon Inorganic materials 0.000 claims description 45
- 229910052757 nitrogen Inorganic materials 0.000 claims description 41
- 125000001424 substituent group Chemical group 0.000 claims description 35
- 150000002431 hydrogen Chemical class 0.000 claims description 31
- -1 OH Chemical class 0.000 claims description 30
- 229920006395 saturated elastomer Polymers 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
- 229910052760 oxygen Inorganic materials 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 29
- 229910052717 sulfur Inorganic materials 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 24
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 239000012453 solvate Substances 0.000 claims description 15
- RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 8
- 230000009385 viral infection Effects 0.000 claims description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 239000006260 foam Substances 0.000 claims description 3
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- 206010035664 Pneumonia Diseases 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 206010057190 Respiratory tract infections Diseases 0.000 claims 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 6
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims 2
- 229920000728 polyester Polymers 0.000 claims 2
- 239000004575 stone Substances 0.000 claims 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- 229910021556 Chromium(III) chloride Inorganic materials 0.000 claims 1
- 101100113998 Mus musculus Cnbd2 gene Proteins 0.000 claims 1
- 230000010933 acylation Effects 0.000 claims 1
- 238000005917 acylation reaction Methods 0.000 claims 1
- QSWDMMVNRMROPK-UHFFFAOYSA-K chromium(3+) trichloride Chemical compound [Cl-].[Cl-].[Cl-].[Cr+3] QSWDMMVNRMROPK-UHFFFAOYSA-K 0.000 claims 1
- 239000011636 chromium(III) chloride Substances 0.000 claims 1
- 235000007831 chromium(III) chloride Nutrition 0.000 claims 1
- 229940088597 hormone Drugs 0.000 claims 1
- 239000005556 hormone Substances 0.000 claims 1
- 101150061302 och1 gene Proteins 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 122
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 113
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 104
- 239000000543 intermediate Substances 0.000 description 97
- 238000003786 synthesis reaction Methods 0.000 description 93
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 92
- 230000015572 biosynthetic process Effects 0.000 description 92
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 79
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
- 239000000243 solution Substances 0.000 description 71
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 62
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 61
- 239000002904 solvent Substances 0.000 description 56
- 229910001868 water Inorganic materials 0.000 description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- 235000019439 ethyl acetate Nutrition 0.000 description 39
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 36
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 34
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 238000006243 chemical reaction Methods 0.000 description 31
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 31
- 239000007787 solid Substances 0.000 description 31
- 239000012044 organic layer Substances 0.000 description 30
- 239000000047 product Substances 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 26
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- 239000002585 base Chemical class 0.000 description 24
- 125000004429 atom Chemical group 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 21
- 241000725643 Respiratory syncytial virus Species 0.000 description 20
- 239000012267 brine Substances 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- 238000011282 treatment Methods 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- 229910000104 sodium hydride Inorganic materials 0.000 description 18
- 239000002253 acid Substances 0.000 description 17
- 229910000027 potassium carbonate Inorganic materials 0.000 description 17
- 239000012634 fragment Substances 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 16
- 125000003003 spiro group Chemical group 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 14
- 229910000024 caesium carbonate Inorganic materials 0.000 description 14
- 239000003054 catalyst Substances 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
- 239000012312 sodium hydride Substances 0.000 description 14
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 13
- 206010061603 Respiratory syncytial virus infection Diseases 0.000 description 13
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 11
- 150000004820 halides Chemical class 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- 239000007864 aqueous solution Substances 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- 125000003226 pyrazolyl group Chemical group 0.000 description 10
- 150000003254 radicals Chemical class 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- 150000001298 alcohols Chemical class 0.000 description 9
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 9
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 239000008194 pharmaceutical composition Substances 0.000 description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- 230000002285 radioactive effect Effects 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 150000004985 diamines Chemical class 0.000 description 8
- 239000003937 drug carrier Substances 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- FOZVXADQAHVUSV-UHFFFAOYSA-N 1-bromo-2-(2-bromoethoxy)ethane Chemical compound BrCCOCCBr FOZVXADQAHVUSV-UHFFFAOYSA-N 0.000 description 7
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 7
- 208000036142 Viral infection Diseases 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 7
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 7
- 125000001309 chloro group Chemical group Cl* 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 239000003208 petroleum Substances 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 7
- 229940086542 triethylamine Drugs 0.000 description 7
- XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 6
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- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- 229910052727 yttrium Inorganic materials 0.000 description 6
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- 230000005526 G1 to G0 transition Effects 0.000 description 5
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 5
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- 125000000623 heterocyclic group Chemical group 0.000 description 5
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 5
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- 230000000670 limiting effect Effects 0.000 description 5
- 239000012280 lithium aluminium hydride Substances 0.000 description 5
- 125000001624 naphthyl group Chemical group 0.000 description 5
- 150000007530 organic bases Chemical class 0.000 description 5
- KVJHBRRDBGTETK-UHFFFAOYSA-N spiro[1h-pyrrolo[2,3-c]pyridine-3,4'-oxane]-2-one Chemical compound O=C1NC2=CN=CC=C2C11CCOCC1 KVJHBRRDBGTETK-UHFFFAOYSA-N 0.000 description 5
- VCWXWCKINURMLB-UHFFFAOYSA-N spiro[1h-pyrrolo[2,3-c]pyridine-3,4'-thiane]-2-one Chemical compound O=C1NC2=CN=CC=C2C11CCSCC1 VCWXWCKINURMLB-UHFFFAOYSA-N 0.000 description 5
- VJABSSGXEWXCLY-UHFFFAOYSA-N 3-methylsulfonylpropylazanium;chloride Chemical compound Cl.CS(=O)(=O)CCCN VJABSSGXEWXCLY-UHFFFAOYSA-N 0.000 description 4
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- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 4
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- AWZDCIMIGRPVIV-UHFFFAOYSA-N spiro[1h-pyrrolo[3,2-c]pyridine-3,4'-oxane]-2-one Chemical compound O=C1NC2=CC=NC=C2C11CCOCC1 AWZDCIMIGRPVIV-UHFFFAOYSA-N 0.000 description 4
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- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
- KFSMQSHAWYERIP-UHFFFAOYSA-N 1,3-dihydropyrrolo[3,2-c]pyridin-2-one;hydrobromide Chemical compound Br.N1=CC=C2NC(=O)CC2=C1 KFSMQSHAWYERIP-UHFFFAOYSA-N 0.000 description 3
- YUYZEKDRDBWNGG-UHFFFAOYSA-N 1-bromo-2-(1-bromopropan-2-yloxy)propane Chemical compound BrCC(C)OC(C)CBr YUYZEKDRDBWNGG-UHFFFAOYSA-N 0.000 description 3
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- IEPPRLPXMAIDLY-UHFFFAOYSA-N 2',6'-dimethylspiro[1h-pyrrolo[2,3-c]pyridine-3,4'-oxane]-2-one Chemical compound C1C(C)OC(C)CC21C1=CC=NC=C1NC2=O IEPPRLPXMAIDLY-UHFFFAOYSA-N 0.000 description 3
- MTPMSDUHSIEEEB-UHFFFAOYSA-N 3,3,7-tribromo-1h-pyrrolo[3,2-c]pyridin-2-one Chemical compound BrC1=CN=CC2=C1NC(=O)C2(Br)Br MTPMSDUHSIEEEB-UHFFFAOYSA-N 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- CZUGFKJYCPYHHV-UHFFFAOYSA-N 3-methylthiopropanol Chemical compound CSCCCO CZUGFKJYCPYHHV-UHFFFAOYSA-N 0.000 description 3
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- XAXNUOPVVXIRSV-UHFFFAOYSA-N 4-fluorospiro[1h-indole-3,4'-oxane]-2-one Chemical compound C1=2C(F)=CC=CC=2NC(=O)C21CCOCC2 XAXNUOPVVXIRSV-UHFFFAOYSA-N 0.000 description 3
- DOLZFTDFWWBNEN-UHFFFAOYSA-N 5-fluorospiro[1h-indole-3,4'-oxane]-2-one Chemical compound C12=CC(F)=CC=C2NC(=O)C21CCOCC2 DOLZFTDFWWBNEN-UHFFFAOYSA-N 0.000 description 3
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- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical class C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
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- OGBINJLTBZWRRB-UHFFFAOYSA-N methyl 2,2,2-trichloroethanimidate Chemical compound COC(=N)C(Cl)(Cl)Cl OGBINJLTBZWRRB-UHFFFAOYSA-N 0.000 description 1
- NZTCVGHPDWAALP-UHFFFAOYSA-N methyl 2,2-dimethoxyacetate Chemical compound COC(OC)C(=O)OC NZTCVGHPDWAALP-UHFFFAOYSA-N 0.000 description 1
- JZXJFIAQMKODSL-UHFFFAOYSA-N methyl 5-chloro-1-(4-fluorobutyl)pyrrolo[3,2-b]pyridine-2-carboxylate Chemical compound ClC1=CC=C2N(CCCCF)C(C(=O)OC)=CC2=N1 JZXJFIAQMKODSL-UHFFFAOYSA-N 0.000 description 1
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- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 229910000069 nitrogen hydride Inorganic materials 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
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- 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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- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
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- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
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- SIOXPEMLGUPBBT-UHFFFAOYSA-M picolinate Chemical compound [O-]C(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-M 0.000 description 1
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- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
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- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 150000003413 spiro compounds Chemical class 0.000 description 1
- NZHWYOLXENRFJZ-UHFFFAOYSA-N spiro[1h-indole-3,3'-azetidine]-2-one Chemical compound O=C1NC2=CC=CC=C2C11CNC1 NZHWYOLXENRFJZ-UHFFFAOYSA-N 0.000 description 1
- DIBPKWQRMFSZTH-UHFFFAOYSA-N spiro[1h-indole-3,3'-cyclobutane]-1',2-dione Chemical compound C1C(=O)CC21C1=CC=CC=C1NC2=O DIBPKWQRMFSZTH-UHFFFAOYSA-N 0.000 description 1
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- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
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- 238000007910 systemic administration Methods 0.000 description 1
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- 231100000211 teratogenicity Toxicity 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- YODZTKMDCQEPHD-UHFFFAOYSA-N thiodiglycol Chemical compound OCCSCCO YODZTKMDCQEPHD-UHFFFAOYSA-N 0.000 description 1
- 125000001166 thiolanyl group Chemical group 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
- C07F9/65068—Five-membered rings having the nitrogen atoms in positions 1 and 3 condensed with carbocyclic rings or carbocyclic ring systems
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- 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
- 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
- C07D471/10—Spiro-condensed systems
-
- 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
- C07D471/12—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 three hetero rings
- C07D471/20—Spiro-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
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- 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
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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- 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
- C07D491/12—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 three hetero rings
- C07D491/20—Spiro-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/20—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- Chemical & Material Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Epidemiology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Claims (5)
- RpbaítálmC ágéoypoatokL (Rl) képié tű vegyülök (RÍ) vagy bármely sztereoisomar formája, ahol: HMjokotte égy allfeth '{φ*.φ%Μ}> (dïlspletah hâmialylks aMflntí heisrooíkius'oÉtclbgyík X joimpse égytBÉÉP Rlgplispül C vagy Mi: mml « mogköMssek hop legalább két X jelentése C; R'*, R*R,C vagyR;d nùadogy lkéo«k jalaotése egymástól. ihggetlenül a kbvetkeísökblíi álló csoportból választolt: R balogéra CVQ.alki), OGctklo&lkih CpCsalkiloxi, N{R% CO(R’}, CRNH2s CÄÄ CM, C(-NOH)Nl-fo C<~NOCH;)NH?, CrNfONHï» CF> és OCFp Ru> vagy Ríd biátvyXk, ha az, X amelyhez; kapcsolódik N-t jelent; ihliitdopik :R4 jelentése r'CIR%%-R'X •m jeleÄse egész «z&ft 94Ê tB&l: mindegyik R3 jsleolése opppfól foggeíjenükakbvetkezhkb^ álló csoportból váláson: 11, halogén, art! hctoporth Crkkalkjl, Cr€ ;dkloalkÜ, CrCkoikiioai éssÚD{R’).; mindegyik :R* jelentése egymástól Hlggetlenhla következekből álló csoportból váíss^oth H, DrQalkfk COOC1-1, es COKHSO^CR; j&bntÄ ï&MvefkeâiihÔi álló csoportból válásodon: ]r| CrCsalkil, OH, CVCpIkiloxg NR, NHSÖ.;N{Cr€pJRd|,MHSO^ N H F O 0 C 5 ' GM k loa 1 k il} és NR* Ri0; mindegyik Rs és Rv jelentése egymásból Rtggetlenül a követke Kokból álló csoportból választott: H, €*-Cnsdkil és CVCbcikloalktl; vagy R8 és Hs> együtt egy 4-6-(80:0 telített gyűrűt képez, amely adott esetben egy vagy (öbb hetetoatomot tartalmaz a következőkből álló csoportból választva: N> S és<|p mindegyik R!<J jelentése egymástól függetlenül a következőkből álló csoportból választott; R halogén, OH, CN, OCR €R €rC;, alkll, R-CMkloalkil C(<>)CrC,afkil CROjCr Cbclkioalkil CRö)NRsR\ C(==0}0R\ SO;:Rs, C{~0)N(Rs)S0:.R*, C(«0)N( Rs)S02N<R8R'í}( NR*É$, NR^CROjOR9. OC("-O)R8, O-benzil. NR*SÖiR\ SO;NR^? $OjRssÄRO)NRsR\ ÍX'«))NR*R1\ NCR’jCMlNCRV), Rn, d-ö-tagn teiltet .gyüröx amely egy oxigénatomot tartalmaz, IC* jelentése feall, piridinll vagy pimzolik melyektninéçpl&ÿ.»$pthgs$f>et^ætfbgÂnàltMtéte:pr vagy több, a következőkből álló csoportból egymástól függetlenüliválasztoít: szcbsztllnensséi: Ob, CR, OCHí, OGb\ és habgén; BC jelentése CS -C* alkll vagy cyC?äklo&lkil; melyek ntnóéiylké szbbsHitltáltegy vagy több, & kő-vetkezőkből álló csoportból egymástól füg.|íeí 1 e?Ulf v^l«SîKbôtt öístit; €1¾¾ ¾¾ 06¾ DCFs és halogén; mindegyIk R jelentése epmásiöl Rlggetlénll C vagy N; :i^|.i'me^Ötésse^;ho^;léjpMbbvkét Z jelentése C; Q és ¥ mindegyikének jelenÄe egymástői föggÄsii-'C^i-äOasVagy CR%*S;. p és s jelentése egymástól függetlenül egész szám Ö-tól 3-ig, ahol p és s összege legalább 2, és ha p :K 0 vagy s Ö, akkor a *-ga! jelzett szénatom közvetlenül kötődik W-hez; R^ és R2' a kővetkezőkből álló esnpofiboi választott: hidrogén*, hldrexit Ci-Csalkl'H Cs-Cveikloplkil, 01¾ OCR, OCFs és halngÉi l’O’ jelentése a kővetkezőkből álló csoportból választott: hidrogén, hidrofil, CrCmlklí, OrCjCÍklo·· alklí, CFF, OCR, OCF;; és halogén; W jelentése a kővetkezőkből álló csoportból választott: SO, S02, S, C, O és N, ahol ez a C vagy N adott esetben szuhsziituák egy vagy több RB-msl; Ín* jelentése a kővetkezőkből álló csoportból ^ál^^^lídrőgŐüx.hldiétxtl,. Cí-Cplkil, ürß?Älo-aikll, Cs>Cpiklt-R24, SOjR2<· SOíNCR-V Ml,. bçë^l^C«>)OR24,M^ CRÖ)N(R::4),, Ο0(-ΰ}Ν«ΪΛ);=. P{-0j-{0-C;-€%~alkil}2, N(R?;t)2, NR^CRPpR24, í^^CC^lMCÉf^NR^SÖsíR.“1 és 4-6-tagu telftettgynrtl, amely Mrately aril vagy heteroaril adott zofchöl álló csoportból választott egy vagy több szaisztlnenssel: halogén. OR CN, OCR; :R^ jélentése a kőveimzö esoipríből választott: bídregén, OH, halogén, CrCplkil, €rCptkbalMl, C(^O): Ci-Cplkil;, CROj C;rCí«íkloalkii, Ml, heteroMl, benzil, és d-Ö-tagn felheít gytinl, amely egy öxígéMómöttartaN85í? ahol bármely ilyen Çj-Qalkil cyCjcikloalkih €{*<>) Cs*C«aMs C(~0) Cs'Cjdkla&íkik aril, heterogri!, beozii adott esetben-szahsziiiuáh s kővetkezőkből álló oso* portból: választott egy vagy tőbbszubsztituesssel; halogén, CFj, OH, CN, OChk 0€(~:O)Cl-yés legalább egy €N csoporttal szobsztitnák Cp-CjalkU; K'" jelentése a kivetkezőkből álló csoportból választott: hidrogén és Cä*C3 alkik aril jelentése léről vagy nttöalemkhetsroarü jakmtése tnonocikltssos 5-6-tagú aromás heteroeikkts, amely s kővetkezőkből álló esopotl-bői egymástól függetlenül választott egy vagy több heteroatomof tartalmaz: 0, S és N; vagy hleskmsos b-l 2nagu aromás heteroelkfus. amely a következőkből álló csoportból egymástól Rlggétle-nül választott egy vagy több heteroatomot tartalmaz: Cg S és M; azzal a megkötéssel, hogy Hef nem telel meg a d(s) képletnek ő(x) tol a megkötéssel, hogy ha Hét (a) képletig akkor legalább az egyik Rí:í szubsziituens jelentése halo, vagy ha Hét (b) képleté, akkor legalább az egyik R!pszobszttmes)S jelentése haló, V«tgy győgyszereszeítleg eitogadható ttddieiós sója vagy szolvátja·
- 2, Az L igénypont szerintit R!) képlett! vegyidet vagy bármely sztereotzomer tormája. ahol Hét jelentése egy alábbi itt), (b). le), (dj képletek bármelyike szerinti heíeroeikUts:mtödegyik X jelentése egymástól friggetleníÓ C vagy N; azzal a. megkötéssel, hogy legalább két X jelentése C; Rlä, Rli\ Rls vagy Riÿ mmdegyikének jelentése egymástól fhggetieoöí a kővetkezőkből állő csoportból választott: H, halogén, Cr€#fk.iL CmC^îkilosg Cf3 és OCFg llíb vagy Rls} hiányzik, ItaszX amelyhez kapcsolódik N-t jelem; mindegyik Ré jelentése ^(CRaR\rRu't m jelentése egésg §tám 2rtol: árig; mindegyik R2 jelentése II, halogén vagy CjCsaÍk!l; mindegyik E* Is E* jelentése egymástól feggedenüi a következőkből álló csoportból választott: H és Ci-Cisalkb; mí&dégylk R5S jelentése egymástól föggetl^oöl a kóveítexbkból álló: csoportból választott: H, haio-φ> Öli CM, » CF>, CrC;; alksU CrC?c!kbalkl| C(:Mó)ÖR\ ésaOjR^ mindegyik 1 jelentés® egymástól ffiggetlenűl G vagy N< azzal a nfegkötéssel, bog}- legalább kér Z jelentése C; Q és V mindegyikének jelentése egymástól fiiggetlenül CIC'R"' ; p és § jelentése egymástól foggetlenü! égése szánt örtóí Üg, ahol: p és: s dsszsge legalább 2, és ha p -= 0 vagy s ~ Öyakkof a *·'ρί jelesb szénatom kózvetténhl kötődik W-hesg: E'w és R3: jelentése hidrogén; IC2 jelentésé 8: lóvefeezékbtli álló csoportból yájásrtótt;: bibssgéás Mdrtmil, CrCddktl CFi* CGIi, ÖCIi és halogén; W jelentése a következekből: álló csoportból választott: SCl, C. O és N, ahol sa a G vagy M adott esetbe« SKnbsriitoált egy vagy több R^m^R E2S jelentés© a kővetkezőkből álló csoportból válasgtört:: hidrogén, hldroall; CrCplktt,:CrCMiklo-alkií, CrCöa!kil-R2\ S02R:\ S02N{Rs<%y art!, keteroarik CRMójaR·4, Öf#, C(:::0)N(R2 *):a 0C(-0)N{R;m)2> PfeOKÖ.C;-Cö-alküfe M(lP}2, ΗΕ^(~Θ}0ΕΜ, »Η€(:χ0)ΜίΕ^}2 NR5SS02R2í és 4~ó-ntgú teilten gyűrű, amely egy oxigénatomot tartalmaz, ahol bármely ilyen CrCmlkil, QrGblkloalklk aríl vagy Itrieroaril adott esetben szubariitnált a kóvetke-zökhót álló csoportból választott egy vagy több sznbsrtltuenssek balogé«, öli CM, 001¾ R2* jelentése a kivetkező csoportból választott:: hidrogén, OH, halogén, Cb-Rkalkii, CvRiciklordkiL C(:«Öj Ci~ö#lkli C<:::0) CröpádoaMI» srd, heierosrll, benell, és 4~Őrtagórtelitertgyörö, amely egy oxlgénafentöi tartalmaz, ahol bármely ilyen CrCíalkil, CrGRlkloalkii G(~Ü) CrGridkil, C(:~ö) C.vChcikioalkil, aril heieroaril benzit adott esetben szohsztímáit a kOvetkekikböi álló eső-prtbói yáiasztp egy vagy lőbb sgnbsÄenssei: balogén, Ölj, öli Ö| OGH2,ÖC(iSÖ)Cli) ás legalább egy CM csoporttal szubsztkoálí Ci-Csaíkll· R-5 jelentése a keletkezőkből álló esoprtból választolt: hidrogén és Cris aUdiit arII jelentése fenil vagy naftáiéról; hefernaril jelentése irtani!, liofehil, pírldlbii, piridaziní!, plrirnidioii, pirazimf: kinoxailnil, vagy henrirokiazobl; vagy gyógyszefeSirttileg elfógadható artdRlis s<|# vagy szolváija> d. Λ I* igénypont szerinti vg|yö|ek áboiR^'jeiéníése á következőkből álló csoportból; választottl hidrogén, bldtoxII CrQaikil, CrCjeikloaikii, t. -C^lkll^i SO;>R":\ SOi-MCR^h, arü, Héterosril C{::;0)ÖR2!, OR;u, C(-0)R5·, epOjNtiri, és gyűrd, amely egy bármely ilyen Gï-CsalkR, Cf€#liÄ»: arM <m0 Met i5<îî^ &àmmlrnmmmB ésöpörtbő! választót; egy vagy több ssfetSi^: haló- tón OH, CN, OCH>; rí;! jelentése a következő csoportból választott: hidrogén, OH, halogén, OrC#lkd, CrCoeiktokil. C(:::0) CrC«alktl, C(O) tVOákíoaikii, ári! heteroarií, benzti, és 44«ta# telített gyüíig anrelyegy oxigénatomot tartalmaz, ahol bármely ilye?! CrQalkil CrCNcddoalkU, C(-O) CrCeaUcH? C{----0) CrCíCikioalkil, ml, hetefoarli, benzll adott esetben s»?l»szritw#Í:* következőkből Ä-(%&~ poriból választott egy vagy több szubsztítttenssel: halogén, CF*, OH, £$> OCH3, es OGb-OlCií jJ, 4, A? 1. igénypont szerinti (R.Ç képletű vegyidéi, ahol Hot (a’), tb"! i° I vlf>‘ ) képsen!ghnkilépíább égy X jelenlése N> és Rä%I& R'! Rä ’ es R” jelentése m l< ígénypötAban megadotté & Azé!M> ϊφί$ρ9Μα& bá»»#llé:»rMI vegyült, ahol a CbbésRi') képletnél az egyik X jelentés® N. & Egy előző Igénypontok bármelyike szerinti vegyiílei, ahoi R!,\ R" R>v vagy RK mindegyikének je· leölése egymástól #^tlen#a&vefcss^bií.#Íé':ésóprtl^Í váktsztotí: li és balogéi!
- 7, Egy előző igénypontok bármelyike szerinti vegyidet, kitol R,:>, R!‘ II" vagy R " snsndegyikonok jelentése egymástól Ríggetlenől a következőkből H:ié:4SôpoÂÔI-;VâteÂtt:. klót, btótn és Etsop i, Így 4. igénypont szerinti vegyidet,: ahol R*y líb R5· vagyíR^ mindegyikének jelentésé kfe Ő, Így előző igénypontok bármelyike szerinti vepti lét ahol RÍ* jelentése HCH“RV S^-EF* és áhdi tn jfer fentése egész szám I~től4dg és mindegyik ti15 és R-ijélentéss egyitíástól főggetlebtiili. vagy Cr-iUái kíl közöl választott. Itt, Így előző: igánypentolM yegyliet ábo! R· jélentése CjR|g;:alkiiyR^.:
- 11, Egy' eioró lgénypohtôk:Mmteiyike-Mf||ttô''yègyItelsèôrRtv<JM@»tôSëiîiikôÂké^Ôl#ôiSÂ-ôSô*' portból választott: CyC·, alkii, 11 Oil CN, F, CFll, CFS, SOrCrCmlkll és SOjCrC6cikioalkil. ÍIv Egy előző Igénypontok bármelyike szerint!verölet, ahol & vegyidet Rí! RtlI, RÍV, R V, ítYl; vagy RVÍÍ képiéin;vagy bármely roOereoimmer formája. aim! Heg X és Rr> jelentési: az ólom: igénypontok bármelyiké-· ben megadott, II. ä 12, Igénylőm: smrkní vggyüiok ÄI R^'1 hidrogén, hidroxlí, Cr-Cmlkíl CrC',a1kií-Rí4, SO;;Rm; 0-R"\ férni, €{:::0)ORJ4, C(:::Ö)R"5, ahol bármely Ilyen (VQalkil, tollifÄWJ,.Ä tm* ben s^nbsztlínált egy vagy föbb klyólkeM; syobsmitnenssel; 0(¾ halo^ns Ä y&gy CM, 1& At·· I > Igénypont: slii yégyCSleC ahol à vegyidetvagy gyógyszerétszetiieg elfogadható acklíciós sója vagy smivátja, ISv lgy l > ! 4„ igénypontok Mmmlyikó smrintinmgylitel gyógyszerként történő alkalmazásra, Â^ê^^rès^MsxftÂy,. anady pOgyszótészetiléi eifögadháté iordnzót, valamint Inrt0> anyagként gyógyászati lag hatásos nmpnyisggben egy I:d4, igényponiok bármelyiké sggrmR vagyüle-tet tartalma:?..
- 17, Egy 1-14. Igénypontok bármelyike szerinti vem tflet vagy egy 15, igénypont szerinti gyogymasri--saeti kisaimény légéti syoevtians virus fertőzés kezelésében történd alkalmazásra.
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