CN102746240A - 抗感染嘧啶及其用途 - Google Patents
抗感染嘧啶及其用途 Download PDFInfo
- Publication number
- CN102746240A CN102746240A CN2012101675880A CN201210167588A CN102746240A CN 102746240 A CN102746240 A CN 102746240A CN 2012101675880 A CN2012101675880 A CN 2012101675880A CN 201210167588 A CN201210167588 A CN 201210167588A CN 102746240 A CN102746240 A CN 102746240A
- Authority
- CN
- China
- Prior art keywords
- crystal
- dihydro
- phenyl
- dioxo
- pyrimidin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000002924 anti-infective effect Effects 0.000 title description 3
- 150000003230 pyrimidines Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 354
- 150000003839 salts Chemical class 0.000 claims abstract description 100
- 239000000203 mixture Substances 0.000 claims abstract description 66
- 238000000034 method Methods 0.000 claims abstract description 63
- 238000002360 preparation method Methods 0.000 claims abstract description 47
- -1 naphthalene-2-yl Chemical group 0.000 claims description 525
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 216
- 239000013078 crystal Substances 0.000 claims description 127
- DKGVEURLFBZIQL-UHFFFAOYSA-N 4-aminobenzenesulfonamide methane Chemical compound S(=O)(C1=CC=C(C=C1)N)(=O)N.C DKGVEURLFBZIQL-UHFFFAOYSA-N 0.000 claims description 124
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 claims description 124
- 229940124530 sulfonamide Drugs 0.000 claims description 124
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 116
- 159000000000 sodium salts Chemical class 0.000 claims description 104
- 239000002904 solvent Substances 0.000 claims description 92
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 71
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 68
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 62
- 230000015572 biosynthetic process Effects 0.000 claims description 60
- 238000005755 formation reaction Methods 0.000 claims description 60
- 239000012453 solvate Substances 0.000 claims description 55
- 241000711549 Hepacivirus C Species 0.000 claims description 52
- 239000003814 drug Substances 0.000 claims description 51
- 239000004381 Choline salt Substances 0.000 claims description 50
- 235000019417 choline salt Nutrition 0.000 claims description 50
- 150000003248 quinolines Chemical class 0.000 claims description 41
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 38
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 33
- 229940124597 therapeutic agent Drugs 0.000 claims description 21
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 20
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 17
- 241001493065 dsRNA viruses Species 0.000 claims description 17
- 102000014150 Interferons Human genes 0.000 claims description 16
- 108010050904 Interferons Proteins 0.000 claims description 16
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 16
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 16
- 229940079322 interferon Drugs 0.000 claims description 16
- 229960000329 ribavirin Drugs 0.000 claims description 16
- 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 claims description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 15
- 208000005176 Hepatitis C Diseases 0.000 claims description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 239000002512 suppressor factor Substances 0.000 claims description 12
- 241000124008 Mammalia Species 0.000 claims description 5
- 230000001476 alcoholic effect Effects 0.000 claims description 5
- 238000011081 inoculation Methods 0.000 claims description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 3
- 108020004707 nucleic acids Proteins 0.000 claims description 3
- 102000039446 nucleic acids Human genes 0.000 claims description 3
- 150000007523 nucleic acids Chemical class 0.000 claims description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims 8
- 239000003112 inhibitor Substances 0.000 claims 4
- 229960000468 sulfalene Drugs 0.000 claims 4
- KXRZBTAEDBELFD-UHFFFAOYSA-N sulfamethopyrazine Chemical compound COC1=NC=CN=C1NS(=O)(=O)C1=CC=C(N)C=C1 KXRZBTAEDBELFD-UHFFFAOYSA-N 0.000 claims 4
- 230000029812 viral genome replication Effects 0.000 claims 2
- 239000000543 intermediate Substances 0.000 abstract description 8
- 125000000217 alkyl group Chemical group 0.000 description 203
- 150000003254 radicals Chemical class 0.000 description 183
- 229910052736 halogen Inorganic materials 0.000 description 153
- 150000002367 halogens Chemical class 0.000 description 148
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 145
- 125000003545 alkoxy group Chemical group 0.000 description 127
- 239000002585 base Substances 0.000 description 110
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 110
- 239000001257 hydrogen Substances 0.000 description 108
- 229910052739 hydrogen Inorganic materials 0.000 description 108
- 125000000304 alkynyl group Chemical group 0.000 description 102
- 125000002769 thiazolinyl group Chemical group 0.000 description 99
- XLJMAIOERFSOGZ-UHFFFAOYSA-N cyanic acid Chemical compound OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 description 98
- 235000002639 sodium chloride Nutrition 0.000 description 97
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 96
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 91
- 125000004043 oxo group Chemical group O=* 0.000 description 91
- 229910052760 oxygen Inorganic materials 0.000 description 88
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 85
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 78
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 76
- 239000001301 oxygen Substances 0.000 description 75
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 73
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 68
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 60
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 60
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 58
- 239000000243 solution Substances 0.000 description 58
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 55
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 49
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 48
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 47
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
- 239000007787 solid Substances 0.000 description 45
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 44
- 239000000460 chlorine Substances 0.000 description 43
- 150000001336 alkenes Chemical class 0.000 description 42
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 42
- 125000005133 alkynyloxy group Chemical group 0.000 description 42
- 235000019439 ethyl acetate Nutrition 0.000 description 42
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 39
- 229910052801 chlorine Inorganic materials 0.000 description 39
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 39
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 38
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 38
- 229910052794 bromium Inorganic materials 0.000 description 38
- 239000011630 iodine Substances 0.000 description 37
- 229910052740 iodine Inorganic materials 0.000 description 37
- IBGCXOFOCKCBNQ-UHFFFAOYSA-N nitro cyanate Chemical compound [O-][N+](=O)OC#N IBGCXOFOCKCBNQ-UHFFFAOYSA-N 0.000 description 36
- 125000001424 substituent group Chemical group 0.000 description 36
- 229910052757 nitrogen Inorganic materials 0.000 description 35
- 239000000047 product Substances 0.000 description 35
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 33
- 125000002619 bicyclic group Chemical group 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 28
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 28
- 239000003513 alkali Substances 0.000 description 27
- 239000002253 acid Substances 0.000 description 25
- 125000005087 alkynylcarbonyl group Chemical group 0.000 description 25
- 238000003756 stirring Methods 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 21
- 229910052799 carbon Inorganic materials 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 20
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 19
- 230000000875 corresponding effect Effects 0.000 description 18
- 239000011737 fluorine Substances 0.000 description 18
- 229910052731 fluorine Inorganic materials 0.000 description 18
- 125000005843 halogen group Chemical group 0.000 description 18
- 239000011734 sodium Substances 0.000 description 18
- 238000001035 drying Methods 0.000 description 16
- 238000005406 washing Methods 0.000 description 16
- 229910052717 sulfur Inorganic materials 0.000 description 15
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 14
- 125000005197 alkyl carbonyloxy alkyl group Chemical group 0.000 description 14
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 14
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 14
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 13
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 13
- 125000001072 heteroaryl group Chemical group 0.000 description 13
- 230000008569 process Effects 0.000 description 13
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 125000001624 naphthyl group Chemical group 0.000 description 12
- 229910052763 palladium Inorganic materials 0.000 description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 11
- 125000005090 alkenylcarbonyl group Chemical group 0.000 description 11
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 11
- 239000007864 aqueous solution Substances 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 125000004429 atom Chemical group 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 125000001246 bromo group Chemical group Br* 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 10
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- 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 10
- 238000001291 vacuum drying Methods 0.000 description 10
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 9
- 241000700605 Viruses Species 0.000 description 9
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 9
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 8
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 8
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 7
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical class [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 7
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 7
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
- GCUVBACNBHGZRS-UHFFFAOYSA-N cyclopenta-1,3-diene cyclopenta-2,4-dien-1-yl(diphenyl)phosphane iron(2+) Chemical compound [Fe++].c1cc[cH-]c1.c1cc[c-](c1)P(c1ccccc1)c1ccccc1 GCUVBACNBHGZRS-UHFFFAOYSA-N 0.000 description 7
- 238000009826 distribution Methods 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 125000004193 piperazinyl group Chemical group 0.000 description 7
- 235000015320 potassium carbonate Nutrition 0.000 description 7
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000002002 slurry Substances 0.000 description 7
- 125000000547 substituted alkyl group Chemical group 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 7
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 238000006069 Suzuki reaction reaction Methods 0.000 description 6
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 6
- VYLVYHXQOHJDJL-UHFFFAOYSA-K cerium trichloride Chemical compound Cl[Ce](Cl)Cl VYLVYHXQOHJDJL-UHFFFAOYSA-K 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
- 125000003963 dichloro group Chemical group Cl* 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 6
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
- 229910000160 potassium phosphate Inorganic materials 0.000 description 6
- 229940093916 potassium phosphate Drugs 0.000 description 6
- 235000011009 potassium phosphates Nutrition 0.000 description 6
- 125000003226 pyrazolyl group Chemical group 0.000 description 6
- 235000017550 sodium carbonate Nutrition 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
- 238000007872 degassing Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
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- 239000011593 sulfur Substances 0.000 description 1
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- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- KZZHPWMVEVZEFG-UHFFFAOYSA-N tert-butyl n-phenylcarbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC=C1 KZZHPWMVEVZEFG-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002411 thermogravimetry Methods 0.000 description 1
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000003777 thiepinyl group Chemical group 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 208000021510 thyroid gland disease Diseases 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 229950004288 tosilate Drugs 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Images
Classifications
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- 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
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
-
- 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
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- 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
-
- 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
-
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/225—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
-
- 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
- C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D239/22—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
-
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- 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
- C07D401/10—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 carbon chain containing aromatic rings
-
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- 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
- C07D403/10—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 aromatic rings
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- 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
- C07D405/10—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 carbon chain containing aromatic rings
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- 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
- C07D409/10—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 carbon chain containing aromatic rings
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- 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
- C07D413/10—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 carbon chain containing aromatic rings
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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Abstract
Description
化合物 | R5 | 取代基 |
IB-L0-2.4 | -OCH3 | =NN(H)S(O)2CH3 |
IB-L0-2.7 | -H | =NN(H)S(O)2CH3 |
IB-L0-2.9 | -OCH3 | (S)-C(H)2N(H)S(O)2CH3 |
IB-L0-2.10 | -OCH3 | (R)-F和-C(H)2N(H)S(O)2CH3 |
IB-L0-2.12 | -OCH3 | -F和-C(H)2N(H)S(O)2CH3 |
IB-L0-2.15 | -OCH3 | (R)-C(H)2N(H)S(O)2CH3 |
IB-L0-2.17 | -OCH3 | -C(H)2N(H)S(O)2CH3 |
IB-L0-2.20 | -OCH3 | (S)-F和-C(H)2N(H)S(O)2CH3 |
IB-L0-2.22 | -OCH3 | (S)-C(CH3)2N(H)S(O)2CH3 |
IB-L0-2.24 | -OCH3 | =NN(H)C(O)OCH3 |
IB-L0-2.25 | -OCH3 | -CH3和-C(H)2N(H)S(O)2CH3 |
IB-L0-2.29 | -OCH3 | -C(CH3)2N(H)S(O)2CH3 |
IB-L0-2.31 | -OCH3 | -N(H)N(H)S(O)2CH3 |
IB-L0-2.34 | -OCH3 | -C(O)N(H)S(O)2CH3 |
IB-L0-2.36 | -OCH3 | -OH |
IB-L0-2.37 | -OCH3 | (R)-C(CH3)2N(H)S(O)2CH3 |
IB-L0-2.44 | -OCH3 | -N(H)S(O)2CH3 |
IB-L0-2.50 | -OCH3 | =O |
化合物 | R5 | 取代基 |
IB-L0-2.11 | -OCH3 | C(H)2N(H)S(O)2CH3 |
IB-L0-2.21 | -OCH3 | -C(H)2N(CH3)S(O)2CH3 |
IB-L0-2.35 | -Cl | -C(H)2N(H)S(O)2CH3 |
化合物 | 取代基 |
IB-L0-2.18 | -C(H)2N(H)S(O)2CH3 |
IB-L0-2.42 | -CH3 |
化合物 | 1a | 1b | 化合物 | 1a | 1b |
IA-L0-2.1 | C | C | |||
IA-L0-2.2 | B | B | IA-L0-2.3 | C | C |
IA-L0-2.4 | B | B | IA-L0-2.5 | C | C |
IA-L0-2.6 | C | C | IA-L0-2.7 | C | C |
IA-L0-2.8 | B | B | IA-L0-2.9 | A | A |
IA-L0-2.10 | D | D | IB-L0-2.1 | C | C |
IB-L0-2.2 | C | C | IB-L0-2.3 | A | A |
IB-L0-2.4 | A | A | IB-L0-2.5 | B | B |
IB-L0-2.6 | B | B | IB-L0-2.7 | B | B |
IB-L0-2.8 | B | B | IB-L0-2.9 | A | A |
IB-L0-2.10 | A | B | IB-L0-2.11 | A | A |
IB-L0-2.12 | A | B | IB-L0-2.13 | A | B |
IB-L0-2.14 | A | A | IB-L0-2.15 | A | B |
IB-L0-2.16 | A | B | IB-L0-2.17 | A | B |
IB-L0-2.18 | A | B | IB-L0-2.19 | A | B |
IB-L0-2.20 | A | B | IB-L0-2.21 | B | B |
IB-L0-2.22 | B | B | IB-L0-2.23 | B | A |
IB-L0-2.24 | B | B | IB-L0-2.25 | B | B |
IB-L0-2.26 | B | B | IB-L0-2.27 | B | B |
IB-L0-2.28 | B | B | IB-L0-2.29 | B | B |
IB-L0-2.30 | B | B | IB-L0-2.31 | B | B |
IB-L0-2.32 | B | B | IB-L0-2.33 | B | B |
IB-L0-2.34 | B | B | IB-L0-2.35 | B | B |
IB-L0-2.36 | B | C | IB-L0-2.37 | C | C |
IB-L0-2.38 | C | B | IB-L0-2.39 | C | C |
IB-L0-2.40 | C | C | IB-L0-2.41 | C | C |
IB-L0-2.42 | C | C | IB-L0-2.43 | C | C |
IB-L0-2.44 | C | C | IB-L0-2.45 | C | C |
IB-L0-2.46 | C | C | IB-L0-2.47 | D | D |
IB-L0-2.48 | D | D | IB-L0-2.49 | D | D |
IB-L0-2.50 | B | B | IB-L0-2.51 | A | B |
IB-L0-2.52 | A | B | IB-L0-2.53 | A | B |
IB-L0-2.54 | A | B | IB-L0-2.55 | A | B |
IB-L0-2.56 | A | B | IB-L0-2.57 | A | B |
IB-L0-2.58 | A | B | IB-L0-2.59 | A | B |
IB-L0-2.60 | A | B | IB-L0-2.61 | A | B |
IB-L0-2.62 | B | B | IB-L0-2.63 | B | B |
IB-L0-2.64 | B | B | IB-L0-2.65 | B | A |
IB-L0-2.66 | B | B | IB-L0-2.67 | B | B |
IB-L0-2.68 | B | B | IB-L0-2.69 | B | B |
IB-L0-2.70 | B | C | IB-L0-2.71 | C | C |
IB-L0-2.72 | C | C | IB-L0-2.73 | C | C |
IB-L0-2.74 | C | C | IB-L0-2.75 | C | D |
IB-L0-2.76 | C | D | IB-L0-2.77 | D | D |
IB-L0-2.78 | D | D | IB-L0-2.79 | B | B |
化合物 | 1a | 1b | 化合物 | 1a | 1b |
IA-L0-2.1 | D | D | |||
IA-L0-2.2 | C | B | IA-L0-2.3 | C | C |
IA-L0-2.4 | D | C | IA-L0-2.5 | D | D |
IA-L0-2.6 | D | D | IA-L0-2.7 | D | C |
IA-L0-2.8 | C | B | IA-L0-2.9 | A | A |
IA-L0-2.10 | ND | ND | IB-L0-2.1 | D | C |
IB-L0-2.2 | D | D | IB-L0-2.3 | A | A |
IB-L0-2.4 | ND | A | IB-L0-2.5 | B | A |
IB-L0-2.6 | C | B | IB-L0-2.7 | C | B |
IB-L0-2.8 | ND | B | IB-L0-2.9 | A | A |
IB-L0-2.10 | A | A | IB-L0-2.11 | B | A |
IB-L0-2.12 | B | A | IB-L0-2.13 | B | A |
IB-L0-2.14 | C | B | IB-L0-2.15 | C | B |
IB-L0-2.16 | C | A | IB-L0-2.17 | B | A |
IB-L0-2.18 | C | B | IB-L0-2.19 | B | B |
IB-L0-2.20 | C | B | IB-L0-2.21 | C | B |
IB-L0-2.22 | C | B | IB-L0-2.23 | C | B |
IB-L0-2.24 | B | B | IB-L0-2.25 | C | B |
IB-L0-2.26 | D | C | IB-L0-2.27 | C | B |
IB-L0-2.28 | D | C | IB-L0-2.29 | C | B |
IB-L0-2.30 | C | B | IB-L0-2.31 | C | B |
IB-L0-2.32 | C | B | IB-L0-2.33 | C | C |
IB-L0-2.34 | D | C | IB-L0-2.35 | D | C |
IB-L0-2.36 | C | B | IB-L0-2.37 | D | C |
IB-L0-2.38 | D | D | IB-L0-2.39 | D | C |
IB-L0-2.40 | D | C | IB-L0-2.41 | C | C |
IB-L0-2.42 | C | C | IB-L0-2.43 | D | C |
IB-L0-2.44 | D | D | IB-L0-2.45 | D | C |
IB-L0-2.46 | ND | ND | IB-L0-2.47 | ND | ND |
IB-L0-2.48 | ND | ND | IB-L0-2.49 | ND | ND |
IB-L0-2.50 | C | C | IB-L0-2.51 | B | A |
IB-L0-2.52 | B | A | IB-L0-2.53 | B | B |
IB-L0-2.54 | B | B | IB-L0-2.55 | B | A |
IB-L0-2.56 | C | A | IB-L0-2.57 | C | B |
IB-L0-2.58 | B | A | IB-L0-2.59 | C | B |
IB-L0-2.60 | C | B | IB-L0-2.61 | C | B |
IB-L0-2.62 | C | B | IB-L0-2.63 | C | B |
IB-L0-2.64 | C | A | IB-L0-2.65 | C | B |
IB-L0-2.66 | C | B | IB-L0-2.67 | C | B |
IB-L0-2.68 | D | C | IB-L0-2.69 | C | B |
IB-L0-2.70 | D | C | IB-L0-2.71 | C | B |
IB-L0-2.72 | D | C | IB-L0-2.73 | C | C |
IB-L0-2.74 | D | C | IB-L0-2.75 | D | D |
IB-L0-2.76 | ND | ND | IB-L0-2.77 | ND | ND |
IB-L0-2.78 | ND | ND | IB-L0-2.79 | C | C |
Claims (50)
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US97288107P | 2007-09-17 | 2007-09-17 | |
US60/972881 | 2007-09-17 | ||
US60/972,881 | 2007-09-17 | ||
US9679208P | 2008-09-13 | 2008-09-13 | |
US61/096792 | 2008-09-13 | ||
US61/096,792 | 2008-09-13 | ||
CN200880113534.8A CN101842360B (zh) | 2007-09-17 | 2008-09-17 | 抗感染嘧啶及其用途 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CN200880113534.8A Division CN101842360B (zh) | 2007-09-17 | 2008-09-17 | 抗感染嘧啶及其用途 |
Publications (2)
Publication Number | Publication Date |
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CN102746240A true CN102746240A (zh) | 2012-10-24 |
CN102746240B CN102746240B (zh) | 2017-10-03 |
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