CN1697650B - 非核苷类逆转录酶抑制剂 - Google Patents
非核苷类逆转录酶抑制剂 Download PDFInfo
- Publication number
- CN1697650B CN1697650B CN038243377A CN03824337A CN1697650B CN 1697650 B CN1697650 B CN 1697650B CN 038243377 A CN038243377 A CN 038243377A CN 03824337 A CN03824337 A CN 03824337A CN 1697650 B CN1697650 B CN 1697650B
- Authority
- CN
- China
- Prior art keywords
- alkyl
- substituted
- group
- chemical compound
- aryl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 title description 7
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 155
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- -1 substituted-phenyl Chemical group 0.000 claims description 69
- 125000000217 alkyl group Chemical group 0.000 claims description 64
- 125000000623 heterocyclic group Chemical group 0.000 claims description 62
- 125000003118 aryl group Chemical group 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 54
- 239000001257 hydrogen Substances 0.000 claims description 53
- 229910052736 halogen Inorganic materials 0.000 claims description 43
- 150000002367 halogens Chemical class 0.000 claims description 42
- 125000001424 substituent group Chemical group 0.000 claims description 33
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 28
- 125000000304 alkynyl group Chemical group 0.000 claims description 26
- 241000700605 Viruses Species 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 229940111121 antirheumatic drug quinolines Drugs 0.000 claims description 17
- 150000003248 quinolines Chemical class 0.000 claims description 17
- 125000001624 naphthyl group Chemical group 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 150000002460 imidazoles Chemical class 0.000 claims description 12
- 150000002537 isoquinolines Chemical class 0.000 claims description 12
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000003107 substituted aryl group Chemical group 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 9
- 230000009467 reduction Effects 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 7
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 238000009395 breeding Methods 0.000 claims description 6
- 230000001488 breeding effect Effects 0.000 claims description 6
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000004442 acylamino group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 3
- 125000005257 alkyl acyl group Chemical group 0.000 claims description 3
- 150000004693 imidazolium salts Chemical class 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 abstract description 45
- 239000002777 nucleoside Substances 0.000 abstract description 19
- 150000003833 nucleoside derivatives Chemical class 0.000 abstract description 18
- 239000003112 inhibitor Substances 0.000 abstract description 15
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 abstract description 4
- OWIKHYCFFJSOEH-UHFFFAOYSA-N Isocyanic acid Chemical class N=C=O OWIKHYCFFJSOEH-UHFFFAOYSA-N 0.000 abstract description 4
- 238000001727 in vivo Methods 0.000 abstract description 3
- 238000000338 in vitro Methods 0.000 abstract description 2
- 102100034343 Integrase Human genes 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 78
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 68
- 239000000243 solution Substances 0.000 description 61
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- 238000000034 method Methods 0.000 description 56
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- 239000002585 base Substances 0.000 description 46
- 102100034349 Integrase Human genes 0.000 description 45
- 125000004429 atom Chemical group 0.000 description 44
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 41
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
- 125000005647 linker group Chemical group 0.000 description 38
- 239000000376 reactant Substances 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- 229910052717 sulfur Inorganic materials 0.000 description 33
- 238000013461 design Methods 0.000 description 32
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 32
- 238000000746 purification Methods 0.000 description 31
- 210000004027 cell Anatomy 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
- 241000725303 Human immunodeficiency virus Species 0.000 description 27
- 239000012044 organic layer Substances 0.000 description 26
- 229910052760 oxygen Inorganic materials 0.000 description 25
- 239000007787 solid Substances 0.000 description 23
- 239000010410 layer Substances 0.000 description 22
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 238000004440 column chromatography Methods 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- 125000003342 alkenyl group Chemical group 0.000 description 18
- 230000008569 process Effects 0.000 description 18
- 150000001412 amines Chemical class 0.000 description 17
- 229910052938 sodium sulfate Inorganic materials 0.000 description 17
- 235000011152 sodium sulphate Nutrition 0.000 description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 14
- 150000001721 carbon Chemical group 0.000 description 14
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- 125000005842 heteroatom Chemical group 0.000 description 13
- 108060001084 Luciferase Proteins 0.000 description 12
- 125000000392 cycloalkenyl group Chemical group 0.000 description 12
- 238000003810 ethyl acetate extraction Methods 0.000 description 12
- 239000000651 prodrug Substances 0.000 description 12
- 229940002612 prodrug Drugs 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 150000003852 triazoles Chemical class 0.000 description 12
- 229960004756 ethanol Drugs 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- 239000005089 Luciferase Substances 0.000 description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 10
- 230000008878 coupling Effects 0.000 description 10
- 238000010168 coupling process Methods 0.000 description 10
- 238000005859 coupling reaction Methods 0.000 description 10
- 238000001556 precipitation Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000006227 byproduct Substances 0.000 description 9
- 229940042396 direct acting antivirals thiosemicarbazones Drugs 0.000 description 9
- 238000000935 solvent evaporation Methods 0.000 description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- 235000002639 sodium chloride Nutrition 0.000 description 7
- 239000011593 sulfur Chemical group 0.000 description 7
- 238000010189 synthetic method Methods 0.000 description 7
- 230000003612 virological effect Effects 0.000 description 7
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 6
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 6
- 239000007868 Raney catalyst Substances 0.000 description 6
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 6
- 229910000564 Raney nickel Inorganic materials 0.000 description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 150000002430 hydrocarbons Chemical class 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 5
- 208000036142 Viral infection Diseases 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 5
- 230000009385 viral infection Effects 0.000 description 5
- LJAROVLJNWCCPM-UHFFFAOYSA-N 2-chloro-n-(2-chloropyridin-3-yl)acetamide Chemical compound ClCC(=O)NC1=CC=CN=C1Cl LJAROVLJNWCCPM-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 4
- 239000000908 ammonium hydroxide Substances 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine Chemical compound CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000006386 neutralization reaction Methods 0.000 description 4
- NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 description 4
- 229910017604 nitric acid Inorganic materials 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- 230000029812 viral genome replication Effects 0.000 description 4
- 229960002555 zidovudine Drugs 0.000 description 4
- 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 4
- FRLVKAJKOYFHKQ-UHFFFAOYSA-N 1-methyl-4-nitronaphthalene Chemical compound C1=CC=C2C(C)=CC=C([N+]([O-])=O)C2=C1 FRLVKAJKOYFHKQ-UHFFFAOYSA-N 0.000 description 3
- MQFYUZCANYLWEI-UHFFFAOYSA-N 4-methylnaphthalen-1-amine Chemical class C1=CC=C2C(C)=CC=C(N)C2=C1 MQFYUZCANYLWEI-UHFFFAOYSA-N 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- 206010038997 Retroviral infections Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000011262 co‐therapy Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical compound NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 description 3
- FHWXHTWOJWDSAR-UHFFFAOYSA-N n-(2-bromophenyl)-2-chloroacetamide Chemical compound ClCC(=O)NC1=CC=CC=C1Br FHWXHTWOJWDSAR-UHFFFAOYSA-N 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 125000002971 oxazolyl group Chemical group 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 125000005425 toluyl group Chemical group 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- CBMXCNPQDUJNHT-UHFFFAOYSA-N 1,6-dimethylnaphthalene Chemical compound CC1=CC=CC2=CC(C)=CC=C21 CBMXCNPQDUJNHT-UHFFFAOYSA-N 0.000 description 2
- OFKWHEHUTRXYMT-UHFFFAOYSA-N 1-[4-(dimethylamino)naphthalen-1-yl]-3-prop-2-ynylthiourea Chemical compound C1=CC=C2C(N(C)C)=CC=C(NC(=S)NCC#C)C2=C1 OFKWHEHUTRXYMT-UHFFFAOYSA-N 0.000 description 2
- KUEMIBPMHFKZRJ-UHFFFAOYSA-N 1-ethyl-4-nitronaphthalene Chemical compound C1=CC=C2C(CC)=CC=C([N+]([O-])=O)C2=C1 KUEMIBPMHFKZRJ-UHFFFAOYSA-N 0.000 description 2
- QPUYECUOLPXSFR-UHFFFAOYSA-N 1-methylnaphthalene Chemical compound C1=CC=C2C(C)=CC=CC2=C1 QPUYECUOLPXSFR-UHFFFAOYSA-N 0.000 description 2
- ZAHKVIRLTVQZQD-UHFFFAOYSA-N 2,5,7-trimethyl-8-nitroquinoline Chemical compound CC1=CC(C)=C([N+]([O-])=O)C2=NC(C)=CC=C21 ZAHKVIRLTVQZQD-UHFFFAOYSA-N 0.000 description 2
- AOPBDRUWRLBSDB-UHFFFAOYSA-N 2-bromoaniline Chemical compound NC1=CC=CC=C1Br AOPBDRUWRLBSDB-UHFFFAOYSA-N 0.000 description 2
- UTVZWVRTUIUNLO-UHFFFAOYSA-N 2-chloro-n-(2-methyl-4-sulfamoylphenyl)acetamide Chemical compound CC1=CC(S(N)(=O)=O)=CC=C1NC(=O)CCl UTVZWVRTUIUNLO-UHFFFAOYSA-N 0.000 description 2
- UVZZTECIUXUZEA-UHFFFAOYSA-N 4-methyl-n-(1-methylsulfanyl-2-nitroethenyl)aniline Chemical compound [O-][N+](=O)C=C(SC)NC1=CC=C(C)C=C1 UVZZTECIUXUZEA-UHFFFAOYSA-N 0.000 description 2
- ZFLLHMUWSVFKDE-UHFFFAOYSA-N 5-chloro-2-methyl-8-nitroquinoline Chemical compound ClC1=CC=C([N+]([O-])=O)C2=NC(C)=CC=C21 ZFLLHMUWSVFKDE-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 2
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 2
- ASGOVOHKRBZTAK-UHFFFAOYSA-N C1=CC(=C(C=C1CN)Br)NC(=O)CCl Chemical compound C1=CC(=C(C=C1CN)Br)NC(=O)CCl ASGOVOHKRBZTAK-UHFFFAOYSA-N 0.000 description 2
- LPNCBIIIWGFMSZ-UHFFFAOYSA-N CC1=CC(CC(=C1)C(=O)O)(C2=CC=C(C3=CC=CC=C32)N(C)C)C(=O)O Chemical compound CC1=CC(CC(=C1)C(=O)O)(C2=CC=C(C3=CC=CC=C32)N(C)C)C(=O)O LPNCBIIIWGFMSZ-UHFFFAOYSA-N 0.000 description 2
- 108010041397 CD4 Antigens Proteins 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 102000009410 Chemokine receptor Human genes 0.000 description 2
- 108050000299 Chemokine receptor Proteins 0.000 description 2
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 description 2
- 229940100389 Sulfonylurea Drugs 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229960004748 abacavir Drugs 0.000 description 2
- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000012965 benzophenone Substances 0.000 description 2
- 229940006460 bromide ion Drugs 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 210000004970 cd4 cell Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 229960005319 delavirdine Drugs 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 229960003804 efavirenz Drugs 0.000 description 2
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 2
- 108700004025 env Genes Proteins 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000004519 grease Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 2
- 229960001936 indinavir Drugs 0.000 description 2
- CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- GRHBQAYDJPGGLF-UHFFFAOYSA-N isothiocyanic acid Chemical compound N=C=S GRHBQAYDJPGGLF-UHFFFAOYSA-N 0.000 description 2
- 229960001627 lamivudine Drugs 0.000 description 2
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- QNDPVZDZPKPOHD-UHFFFAOYSA-N n,n,2-trimethyl-8-nitroquinolin-5-amine Chemical compound CC1=CC=C2C(N(C)C)=CC=C([N+]([O-])=O)C2=N1 QNDPVZDZPKPOHD-UHFFFAOYSA-N 0.000 description 2
- HWVHDGFTNBHMQK-UHFFFAOYSA-N n-(1-hydrazinyl-2-nitroethenyl)-4-methylaniline Chemical compound CC1=CC=C(NC(NN)=C[N+]([O-])=O)C=C1 HWVHDGFTNBHMQK-UHFFFAOYSA-N 0.000 description 2
- QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 2
- 229960000689 nevirapine Drugs 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 150000002916 oxazoles Chemical class 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 125000005493 quinolyl group Chemical group 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 2
- 229960001852 saquinavir Drugs 0.000 description 2
- 150000003335 secondary amines Chemical group 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 125000000565 sulfonamide group Chemical group 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 150000003583 thiosemicarbazides Chemical class 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 229940023080 viracept Drugs 0.000 description 2
- QVHJQCGUWFKTSE-YFKPBYRVSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-YFKPBYRVSA-N 0.000 description 1
- QHJMFSMPSZREIF-UHFFFAOYSA-N 1,3-dimethylnaphthalene Chemical compound C1=CC=CC2=CC(C)=CC(C)=C21 QHJMFSMPSZREIF-UHFFFAOYSA-N 0.000 description 1
- NELVJAHLZGRAEF-UHFFFAOYSA-N 1,6-dimethyl-4-nitronaphthalene Chemical compound CC1=CC=C([N+]([O-])=O)C2=CC(C)=CC=C21 NELVJAHLZGRAEF-UHFFFAOYSA-N 0.000 description 1
- HYRFWKJWOMNIKC-UHFFFAOYSA-N 1-(3-bromophenyl)-3-[[5-methyl-4-(4-methylphenyl)-1,2,4-triazol-3-yl]methyl]urea Chemical compound C=1C=C(C)C=CC=1N1C(C)=NN=C1CNC(=O)NC1=CC=CC(Br)=C1 HYRFWKJWOMNIKC-UHFFFAOYSA-N 0.000 description 1
- ZMXIYERNXPIYFR-UHFFFAOYSA-N 1-ethylnaphthalene Chemical compound C1=CC=C2C(CC)=CC=CC2=C1 ZMXIYERNXPIYFR-UHFFFAOYSA-N 0.000 description 1
- ZWZCQZCIZDUWOS-UHFFFAOYSA-N 1-methylsulfanyl-2-nitroethene Chemical group CSC=C[N+]([O-])=O ZWZCQZCIZDUWOS-UHFFFAOYSA-N 0.000 description 1
- NPPPMWQUJJSHIK-UHFFFAOYSA-N 2,4-dimethyl-1-nitronaphthalene Chemical compound C1=CC=CC2=C([N+]([O-])=O)C(C)=CC(C)=C21 NPPPMWQUJJSHIK-UHFFFAOYSA-N 0.000 description 1
- JWVGDDPWYRNGHD-UHFFFAOYSA-N 2,5-dimethyl-8-nitroquinoline Chemical compound CC1=CC=C([N+]([O-])=O)C2=NC(C)=CC=C21 JWVGDDPWYRNGHD-UHFFFAOYSA-N 0.000 description 1
- OPQRSEDPFIFKAS-UHFFFAOYSA-N 2-chloro-5-methylquinoline Chemical class ClC1=CC=C2C(C)=CC=CC2=N1 OPQRSEDPFIFKAS-UHFFFAOYSA-N 0.000 description 1
- DJZMCMGIELTKOI-UHFFFAOYSA-N 2-chloro-n-(2-chloro-4-sulfamoylphenyl)acetamide Chemical compound NS(=O)(=O)C1=CC=C(NC(=O)CCl)C(Cl)=C1 DJZMCMGIELTKOI-UHFFFAOYSA-N 0.000 description 1
- OPZKPLRTPWUXRN-UHFFFAOYSA-N 2-chloro-n-(2-chlorophenyl)acetamide Chemical compound ClCC(=O)NC1=CC=CC=C1Cl OPZKPLRTPWUXRN-UHFFFAOYSA-N 0.000 description 1
- UDAIGHZFMLGNDQ-UHFFFAOYSA-N 2-nitroquinoline Chemical compound C1=CC=CC2=NC([N+](=O)[O-])=CC=C21 UDAIGHZFMLGNDQ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- LHCOVOKZWQYODM-CPEOKENHSA-N 4-amino-1-[(2r,5s)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one;1-[(2r,4s,5s)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1.O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 LHCOVOKZWQYODM-CPEOKENHSA-N 0.000 description 1
- BCOWFSQIFGWBIR-UHFFFAOYSA-N 4-ethylnaphthalen-1-amine Chemical class C1=CC=C2C(CC)=CC=C(N)C2=C1 BCOWFSQIFGWBIR-UHFFFAOYSA-N 0.000 description 1
- KKIGUVBJOHCXSP-UHFFFAOYSA-N 4-phenylthiosemicarbazide Chemical class NNC(=S)NC1=CC=CC=C1 KKIGUVBJOHCXSP-UHFFFAOYSA-N 0.000 description 1
- ZCWXYZBQDNFULS-UHFFFAOYSA-N 5-chloro-2-nitroaniline Chemical compound NC1=CC(Cl)=CC=C1[N+]([O-])=O ZCWXYZBQDNFULS-UHFFFAOYSA-N 0.000 description 1
- IGDYNWKWXUCIJB-UHFFFAOYSA-N 5-methyl-2-nitroaniline Chemical compound CC1=CC=C([N+]([O-])=O)C(N)=C1 IGDYNWKWXUCIJB-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ISGJGCOXMYLRBN-UHFFFAOYSA-N CC1=CC(=C(C=C1)N2C(=NN=C2[N+](=O)[O-])C)C Chemical compound CC1=CC(=C(C=C1)N2C(=NN=C2[N+](=O)[O-])C)C ISGJGCOXMYLRBN-UHFFFAOYSA-N 0.000 description 1
- 206010057248 Cell death Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 108010032976 Enfuvirtide Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 101900297506 Human immunodeficiency virus type 1 group M subtype B Reverse transcriptase/ribonuclease H Proteins 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- SETHSKIRVBKZTB-UHFFFAOYSA-N NC([O])=O Chemical compound NC([O])=O SETHSKIRVBKZTB-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 241000139306 Platt Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 101150104269 RT gene Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 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 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- GLWHPRRGGYLLRV-XLPZGREQSA-N [[(2s,3s,5r)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](N=[N+]=[N-])C1 GLWHPRRGGYLLRV-XLPZGREQSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000005042 acyloxymethyl group Chemical group 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N aminothiocarboxamide Natural products NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000000798 anti-retroviral effect Effects 0.000 description 1
- 229940124522 antiretrovirals Drugs 0.000 description 1
- 239000003903 antiretrovirus agent Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 150000008366 benzophenones Chemical class 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003067 chemokine receptor CCR5 antagonist Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229940014461 combivir Drugs 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical group 0.000 description 1
- 229960002656 didanosine Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- PEASPLKKXBYDKL-FXEVSJAOSA-N enfuvirtide Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(C)=O)[C@@H](C)O)[C@@H](C)CC)C1=CN=CN1 PEASPLKKXBYDKL-FXEVSJAOSA-N 0.000 description 1
- 229960002062 enfuvirtide Drugs 0.000 description 1
- 101150030339 env gene Proteins 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- JLEKJZUYWFJPMB-UHFFFAOYSA-N ethyl 2-methoxyacetate Chemical compound CCOC(=O)COC JLEKJZUYWFJPMB-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003574 free electron Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229940125777 fusion inhibitor Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000003010 ionic group Chemical group 0.000 description 1
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 1
- IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate Chemical compound [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229910000474 mercury oxide Inorganic materials 0.000 description 1
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 238000005497 microtitration Methods 0.000 description 1
- 230000004898 mitochondrial function Effects 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- ISRXMEYARGEVIU-UHFFFAOYSA-N n-methyl-n-propan-2-ylpropan-2-amine Chemical compound CC(C)N(C)C(C)C ISRXMEYARGEVIU-UHFFFAOYSA-N 0.000 description 1
- 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
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 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
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000020978 protein processing Effects 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- 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
- 229920002477 rna polymer Polymers 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229960001203 stavudine Drugs 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 229960004556 tenofovir Drugs 0.000 description 1
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 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
- 238000012360 testing method Methods 0.000 description 1
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940021747 therapeutic vaccine Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000820 toxicity test 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
- 238000001890 transfection Methods 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/84—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| USPCT/US02/26816 | 2002-08-23 | ||
| US0226816 | 2002-08-23 | ||
| PCT/US2003/027433 WO2004030611A2 (en) | 2002-08-23 | 2003-08-22 | Non-nucleoside reverse transcriptase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1697650A CN1697650A (zh) | 2005-11-16 |
| CN1697650B true CN1697650B (zh) | 2010-11-10 |
Family
ID=32067653
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN038243377A Expired - Fee Related CN1697650B (zh) | 2002-08-23 | 2003-08-22 | 非核苷类逆转录酶抑制剂 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US20060135556A1 (enExample) |
| EP (2) | EP1545483B1 (enExample) |
| JP (1) | JP4413781B2 (enExample) |
| CN (1) | CN1697650B (enExample) |
| AT (1) | ATE504294T1 (enExample) |
| AU (2) | AU2003295324B2 (enExample) |
| BR (1) | BR0313747A (enExample) |
| CA (1) | CA2496565C (enExample) |
| DE (1) | DE60336664D1 (enExample) |
| EA (1) | EA009478B1 (enExample) |
| MX (1) | MXPA05002070A (enExample) |
| WO (1) | WO2004030611A2 (enExample) |
| ZA (1) | ZA200502384B (enExample) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1545483B1 (en) * | 2002-08-23 | 2011-04-06 | Ardea Biosciences, Inc. | Non-nucleoside reverse transcriptase inhibitors |
| US7642277B2 (en) * | 2002-12-04 | 2010-01-05 | Boehringer Ingelheim International Gmbh | Non-nucleoside reverse transcriptase inhibitors |
| GB0315111D0 (en) * | 2003-06-27 | 2003-07-30 | Cancer Rec Tech Ltd | Substituted 5-membered ring compounds and their use |
| CA2558224A1 (en) * | 2004-03-08 | 2005-09-22 | Wyeth | Ion channel modulators |
| WO2005090320A2 (en) * | 2004-03-12 | 2005-09-29 | Wyeth | Triazole derivatives and method of using the same to treat hiv infections |
| WO2005115147A2 (en) * | 2004-05-18 | 2005-12-08 | Merck & Co., Inc. | Hiv reverse transcriptase inhibitors |
| US7517998B2 (en) * | 2004-06-01 | 2009-04-14 | Boehringer Ingelheim International Gmbh | Non nucleoside reverse transcriptase inhibitors |
| WO2007050087A1 (en) | 2004-08-25 | 2007-05-03 | Ardea Biosciences, Inc. | N[S(4-aryl-triazol-3-yl)α -mercaptoacetyl]-p-amino benozoic acids AS HIV REVERSE TRANSCRIPTASE INHIBITORS |
| ATE528001T1 (de) | 2004-08-25 | 2011-10-15 | Ardea Biosciences Inc | S-triazolyl-alpha-mercaptoacetanilide als inhibitoren von hiv-umkehrtranskriptase |
| UA95955C2 (ru) * | 2006-07-24 | 2011-09-26 | Кореа Ресерч Инститьют Оф Кемикал Текнолоджи | Ингибиторы обратной транскриптазы вич |
| WO2009030996A1 (en) * | 2007-09-05 | 2009-03-12 | Coley Pharmaceutical Group, Inc. | Triazole compounds as toll-like receptor (tlr) agonists |
| NZ595035A (en) | 2007-11-27 | 2012-11-30 | Ardea Biosciences Inc | Substituted diazole and triazole compounds and compositions and methods of use |
| JP2012502049A (ja) * | 2008-09-04 | 2012-01-26 | アルディア バイオサイエンス，インク． | 尿酸値を調節するための化合物、組成物及びそれを使用する方法。 |
| US8242154B2 (en) | 2008-09-04 | 2012-08-14 | Ardea Biosciences, Inc. | Compounds, compositions and methods of using same for modulating uric acid levels |
| US8173690B2 (en) | 2008-09-04 | 2012-05-08 | Ardea Biosciences, Inc. | Compounds, compositions and methods of using same for modulating uric acid levels |
| WO2010135536A2 (en) | 2009-05-20 | 2010-11-25 | Ardea Biosciences, Inc. | Methods of modulating uric acid levels |
| WO2011046646A2 (en) * | 2009-07-10 | 2011-04-21 | Microbiotix, Inc. | Inhibitors of filovirus entry into host cells |
| US9102614B2 (en) * | 2010-07-02 | 2015-08-11 | Gilead Sciences, Inc. | Naphth-2-ylacetic acid derivatives to treat AIDS |
| CN101899013B (zh) * | 2010-07-12 | 2012-07-25 | 山东大学 | 2-(2-取代芳基-2h-1,2,4-三唑-3-巯基)乙酰胺衍生物及其制备方法与应用 |
| CN103402988B (zh) | 2010-10-25 | 2015-11-25 | 范德比尔特大学 | 用于抑制昆虫宿主感觉的组合物 |
| WO2012154403A2 (en) * | 2011-05-06 | 2012-11-15 | Vanderbilt University | Composition for inhibition of insect sensing |
| ITMI20120786A1 (it) * | 2012-05-09 | 2013-11-10 | Fond Italiana Sclerosi M Ultipla Fism Onlu | Modulatori del recettore gpr17 |
| AR091651A1 (es) | 2012-07-03 | 2015-02-18 | Ardea Biosciences Inc | Elaboracion de acido 2-(5-bromo-4-(4-ciclopropilnaftalen-1-il)-4h-1,2,4-triazol-3-iltio)acetico |
| RU2626003C2 (ru) * | 2014-04-28 | 2017-07-21 | Общество с ограниченной ответственностью "Квантум Фармасьютикалс" | Амид 1,2,4-триазол-3-илтиогликолевой кислоты, обладающий противовирусной активностью, или его фармацевтически приемлемые соли, фармацевтические композиции и их применение для лечения и профилактики гриппа |
| SG11201707879QA (en) | 2015-03-25 | 2017-10-30 | Univ Vanderbilt | Binary compositions as disruptors of orco-mediated odorant sensing |
| TN2017000483A1 (en) | 2015-05-20 | 2019-04-12 | Amgen Inc | Triazole agonists of the apj receptor. |
| WO2017192485A1 (en) | 2016-05-03 | 2017-11-09 | Amgen Inc. | Heterocyclic triazole compounds as agonists of the apj receptor |
| EP3541792B1 (en) | 2016-11-16 | 2020-12-23 | Amgen Inc. | Triazole furan compounds as agonists of the apj receptor |
| US10906890B2 (en) | 2016-11-16 | 2021-02-02 | Amgen Inc. | Triazole phenyl compounds as agonists of the APJ receptor |
| MA46827A (fr) | 2016-11-16 | 2019-09-25 | Amgen Inc | Composés de triazole à substitution cycloalkyle en tant qu'agonistes du récepteur apj |
| WO2018097945A1 (en) | 2016-11-16 | 2018-05-31 | Amgen Inc. | Heteroaryl-substituted triazoles as apj receptor agonists |
| WO2018093580A1 (en) | 2016-11-16 | 2018-05-24 | Amgen Inc. | Triazole pyridyl compounds as agonists of the apj receptor |
| US11191762B2 (en) | 2016-11-16 | 2021-12-07 | Amgen Inc. | Alkyl substituted triazole compounds as agonists of the APJ Receptor |
| WO2019089335A1 (en) | 2017-11-03 | 2019-05-09 | Amgen Inc. | Fused triazole agonists of the apj receptor |
| WO2019213006A1 (en) | 2018-05-01 | 2019-11-07 | Amgen Inc. | Substituted pyrimidinones as agonists of the apj receptor |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0759563B2 (ja) * | 1987-01-28 | 1995-06-28 | 大塚化学株式会社 | ピラゾ−ル誘導体、その製造方法及び該誘導体を有効成分とする除草剤 |
| EP0303301A3 (en) * | 1987-08-14 | 1989-05-17 | Fuji Photo Film Co., Ltd. | Silver halide photographic material |
| US6832996B2 (en) * | 1995-06-07 | 2004-12-21 | Arthrocare Corporation | Electrosurgical systems and methods for treating tissue |
| US6245817B1 (en) * | 1997-02-14 | 2001-06-12 | Bayer Corporation | NPY5 receptor antagonists and methods for using same |
| AU6144098A (en) * | 1997-02-14 | 1998-09-08 | Bayer Corporation | Amide derivatives as selective neuropeptide y receptor antagonists |
| KR100643419B1 (ko) * | 1998-03-27 | 2006-11-10 | 얀센 파마슈티카 엔.브이. | Ｈｉｖ를 억제하는 피리미딘 유도체 |
| AU2217200A (en) * | 1998-12-23 | 2000-07-12 | Neurogen Corporation | 2-amino-9-alkylpurines: gaba brain receptor ligands |
| US6593077B2 (en) * | 1999-03-22 | 2003-07-15 | Special Materials Research And Technology, Inc. | Method of making thin films dielectrics using a process for room temperature wet chemical growth of SiO based oxides on a substrate |
| NZ527864A (en) | 2001-03-02 | 2004-05-28 | Smithkline Beecham Corp | Benzophenones as inhibitors of reverse transcriptase |
| EP1545483B1 (en) * | 2002-08-23 | 2011-04-06 | Ardea Biosciences, Inc. | Non-nucleoside reverse transcriptase inhibitors |
| US7642277B2 (en) * | 2002-12-04 | 2010-01-05 | Boehringer Ingelheim International Gmbh | Non-nucleoside reverse transcriptase inhibitors |
| US20060205026A1 (en) * | 2002-12-19 | 2006-09-14 | Valeant Research & Development | Parallel inducible cell-based kinase screen |
| WO2007050087A1 (en) * | 2004-08-25 | 2007-05-03 | Ardea Biosciences, Inc. | N[S(4-aryl-triazol-3-yl)α -mercaptoacetyl]-p-amino benozoic acids AS HIV REVERSE TRANSCRIPTASE INHIBITORS |
| US8101799B2 (en) * | 2005-07-21 | 2012-01-24 | Ardea Biosciences | Derivatives of N-(arylamino) sulfonamides as inhibitors of MEK |
| US7842836B2 (en) * | 2006-04-11 | 2010-11-30 | Ardea Biosciences | N-aryl-N'alkyl sulfamides as MEK inhibitors |
| WO2007121481A2 (en) * | 2006-04-18 | 2007-10-25 | Ardea Biosciences, Inc. | Pyridone sulfonamides and pyridone sulfamides as mek inhibitors |
| CA2668997C (en) * | 2006-11-09 | 2012-10-09 | Ardea Biosciences, Inc. | 4-cyanophenylamino-substituted bicyclic heterocyclic compounds as hiv inhibitors |
-
2003
- 2003-08-22 EP EP03786506A patent/EP1545483B1/en not_active Expired - Lifetime
- 2003-08-22 AT AT03786506T patent/ATE504294T1/de not_active IP Right Cessation
- 2003-08-22 MX MXPA05002070A patent/MXPA05002070A/es active IP Right Grant
- 2003-08-22 CA CA2496565A patent/CA2496565C/en not_active Expired - Fee Related
- 2003-08-22 CN CN038243377A patent/CN1697650B/zh not_active Expired - Fee Related
- 2003-08-22 AU AU2003295324A patent/AU2003295324B2/en not_active Ceased
- 2003-08-22 EA EA200500399A patent/EA009478B1/ru not_active IP Right Cessation
- 2003-08-22 JP JP2004541500A patent/JP4413781B2/ja not_active Expired - Fee Related
- 2003-08-22 BR BR0313747-3A patent/BR0313747A/pt not_active Application Discontinuation
- 2003-08-22 EP EP11160994A patent/EP2353593B1/en not_active Expired - Lifetime
- 2003-08-22 US US10/526,249 patent/US20060135556A1/en not_active Abandoned
- 2003-08-22 WO PCT/US2003/027433 patent/WO2004030611A2/en not_active Ceased
- 2003-08-22 DE DE60336664T patent/DE60336664D1/de not_active Expired - Lifetime
-
2005
- 2005-03-22 ZA ZA200502384A patent/ZA200502384B/en unknown
-
2008
- 2008-05-02 US US12/114,467 patent/US20080249131A1/en not_active Abandoned
- 2008-11-19 AU AU2008246249A patent/AU2008246249B2/en not_active Ceased
Non-Patent Citations (3)
| Title |
|---|
| j.p. barthwal.synthesis and biological evaluation of substitutedindolyl-1,2,4-triazoles.j.indian .chem. soc,68.1991,68466-469. * |
| saksena r.k. et al.monoamine oxidase and succinate dehydrogenase inhibitoryand anticonvulsant activities of som5-[(N-arylcarbamyl)methylmercapto]-4-phenyl-3-(4-pyridyl)-1,2,4-triazoles..ijndian j.chem.sect b26b 3.1987,26b(3),290-3. |
| saksena r.k. et al.monoamine oxidase and succinate dehydrogenase inhibitoryand anticonvulsant activities of som5-[(N-arylcarbamyl)methylmercapto]-4-phenyl-3-(4-pyridyl)-1,2,4-triazoles..ijndian j.chem.sect b26b 3.1987,26b(3),290-3. * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004030611A2 (en) | 2004-04-15 |
| AU2003295324A1 (en) | 2004-04-23 |
| EP2353593B1 (en) | 2012-08-22 |
| JP2006505543A (ja) | 2006-02-16 |
| US20060135556A1 (en) | 2006-06-22 |
| JP4413781B2 (ja) | 2010-02-10 |
| CA2496565C (en) | 2013-04-02 |
| EP2353593A1 (en) | 2011-08-10 |
| CA2496565A1 (en) | 2004-04-15 |
| EA009478B1 (ru) | 2008-02-28 |
| MXPA05002070A (es) | 2005-07-05 |
| ATE504294T1 (de) | 2011-04-15 |
| WO2004030611A3 (en) | 2004-06-17 |
| AU2008246249B2 (en) | 2010-09-30 |
| DE60336664D1 (de) | 2011-05-19 |
| ZA200502384B (en) | 2007-03-28 |
| EA200500399A1 (ru) | 2005-12-29 |
| AU2008246249A1 (en) | 2008-12-11 |
| EP1545483B1 (en) | 2011-04-06 |
| CN1697650A (zh) | 2005-11-16 |
| BR0313747A (pt) | 2005-06-21 |
| HK1085667A1 (en) | 2006-09-01 |
| EP1545483A2 (en) | 2005-06-29 |
| US20080249131A1 (en) | 2008-10-09 |
| EP1545483A4 (en) | 2009-03-25 |
| AU2003295324B2 (en) | 2008-08-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1697650B (zh) | 非核苷类逆转录酶抑制剂 | |
| JP5457472B2 (ja) | ＨＩＶ逆転写酵素のインヒビターとしてのＳ−トリアゾリルα−メルカプトアセトアニリド | |
| TW409125B (en) | Antivirally active heterocyclic azahexane derivatives | |
| Thanh et al. | Synthesis, biological evaluation and molecular docking study of 1, 2, 3-1H-triazoles having 4H-pyrano [2, 3-d] pyrimidine as potential Mycobacterium tuberculosis protein tyrosine phosphatase B inhibitors | |
| US6541483B2 (en) | Acridone-derived compounds useful as antineoplastic and antiretroviral agents | |
| SK206292A3 (en) | Pharmacologicaly effective hydrazine derivatives and method of their manufacture | |
| JP2001511124A (ja) | エイズ治療薬としての、プロテアーゼ阻害剤およびリバーストランスクリプターゼ阻害剤との３剤組み合わせ物におけるキノキサリン | |
| US7829548B2 (en) | Compounds useful in the treatment of HIV | |
| HUP0303818A2 (hu) | HIV reverz transzkriptáz inhibitorként alkalmazható triciklikus vegyületek és ezeket tartalmazó gyógyszerkészítmények | |
| JP2008526713A (ja) | Ｈｉｖの治療に有用な化合物 | |
| JP2008526713A5 (enExample) | ||
| EP0937067B1 (en) | 1-(3-aminoindazol-5-yl)-3-phenylmethyl-cyclic ureas useful as hiv protease inhibitors | |
| HK1085667B (en) | Non-nucleoside reverse transcriptase inhibitors | |
| KR20000053123A (ko) | (4ｒ,5ｓ,6ｓ,7ｒ)-헥사히드로-1-[5-(3-아미노인다졸)메틸]-3-부틸-5,6-디히드록시-4,7-비스[페닐메틸]-2ｈ-1,3-디아제핀-2-온,이의 제조 방법 및 ｈｉｖ 프로테아제 억제제로서의 용도 | |
| JP2003502423A (ja) | チオフェン−エチル−チオウレア化合物およびｈｉｖの治療におけるその使用 | |
| JP2024504982A (ja) | マラリアを治療するための化合物および方法 | |
| WO2002000614A1 (en) | Aryl compounds, their preparation and their use in therapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1085667 Country of ref document: HK |
|
| ASS | Succession or assignment of patent right |
Owner name: ADIA LIFE SCIENCE CO.,LTD. Free format text: FORMER OWNER: RIBAPHARM INC. Effective date: 20071012 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20071012 Address after: California, USA Applicant after: ARDEA BIOSCIENCES, Inc. Address before: California, USA Applicant before: Valeant Pharmaceuticals North America |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: GR Ref document number: 1085667 Country of ref document: HK |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20101110 Termination date: 20210822 |