CA2496565C - Non-nucleoside reverse transcriptase inhibitors - Google Patents
Non-nucleoside reverse transcriptase inhibitors Download PDFInfo
- Publication number
- CA2496565C CA2496565C CA2496565A CA2496565A CA2496565C CA 2496565 C CA2496565 C CA 2496565C CA 2496565 A CA2496565 A CA 2496565A CA 2496565 A CA2496565 A CA 2496565A CA 2496565 C CA2496565 C CA 2496565C
- Authority
- CA
- Canada
- Prior art keywords
- substituted
- alkyl
- compound
- halogen
- optionally substituted
- 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 173
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 78
- 239000001257 hydrogen Substances 0.000 claims description 71
- 125000000623 heterocyclic group Chemical group 0.000 claims description 69
- 239000000203 mixture Substances 0.000 claims description 67
- 125000000217 alkyl group Chemical group 0.000 claims description 61
- 229910052736 halogen Inorganic materials 0.000 claims description 58
- 150000002367 halogens Chemical class 0.000 claims description 58
- 125000003118 aryl group Chemical group 0.000 claims description 53
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 46
- -1 C1-C10alkyl Chemical group 0.000 claims description 45
- 229910020008 S(O) Inorganic materials 0.000 claims description 40
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 40
- 125000001424 substituent group Chemical group 0.000 claims description 38
- 125000003342 alkenyl group Chemical group 0.000 claims description 32
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 32
- 125000000304 alkynyl group Chemical group 0.000 claims description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 27
- 125000003107 substituted aryl group Chemical group 0.000 claims description 24
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 230000003612 virological effect Effects 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 17
- 239000000460 chlorine Substances 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 150000003248 quinolines Chemical class 0.000 claims description 16
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 15
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 15
- 125000001624 naphthyl group Chemical group 0.000 claims description 15
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical class C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 10
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 150000002460 imidazoles Chemical class 0.000 claims description 8
- 229910052740 iodine Chemical group 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 5
- 125000003368 amide group Chemical group 0.000 claims description 4
- 229910052794 bromium Inorganic materials 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
- 150000003573 thiols Chemical group 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- 150000001356 alkyl thiols Chemical group 0.000 claims description 3
- 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 claims description 3
- 239000004305 biphenyl Substances 0.000 claims description 3
- 235000010290 biphenyl Nutrition 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000005561 phenanthryl group Chemical group 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 13
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 9
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 9
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims 9
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 239000011630 iodine Chemical group 0.000 claims 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 abstract description 47
- 239000003112 inhibitor Substances 0.000 abstract description 15
- 238000011282 treatment Methods 0.000 abstract description 12
- 238000000338 in vitro Methods 0.000 abstract description 10
- 238000001727 in vivo Methods 0.000 abstract description 9
- 239000002777 nucleoside Substances 0.000 abstract description 8
- 150000003833 nucleoside derivatives Chemical class 0.000 abstract description 7
- OWIKHYCFFJSOEH-UHFFFAOYSA-N Isocyanic acid Chemical class N=C=O OWIKHYCFFJSOEH-UHFFFAOYSA-N 0.000 abstract description 4
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 abstract description 3
- 102100034343 Integrase Human genes 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 79
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 54
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- 102100034349 Integrase Human genes 0.000 description 47
- 125000004429 atom Chemical group 0.000 description 44
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 40
- 238000000034 method Methods 0.000 description 37
- 239000002904 solvent Substances 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- 125000005647 linker group Chemical group 0.000 description 33
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 32
- 229940093499 ethyl acetate Drugs 0.000 description 30
- 235000019439 ethyl acetate Nutrition 0.000 description 30
- 241000725303 Human immunodeficiency virus Species 0.000 description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- 239000012044 organic layer Substances 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 24
- 239000007787 solid Substances 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
- 239000010410 layer Substances 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 19
- 229910052938 sodium sulfate Inorganic materials 0.000 description 19
- 235000011152 sodium sulphate Nutrition 0.000 description 19
- 230000002401 inhibitory effect Effects 0.000 description 16
- 229910000027 potassium carbonate Inorganic materials 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 230000005764 inhibitory process Effects 0.000 description 15
- 125000005842 heteroatom Chemical group 0.000 description 14
- 235000011181 potassium carbonates Nutrition 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 13
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
- 125000000392 cycloalkenyl group Chemical group 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 11
- 239000000651 prodrug Substances 0.000 description 11
- 229940002612 prodrug Drugs 0.000 description 11
- 208000031886 HIV Infections Diseases 0.000 description 10
- 108060001084 Luciferase Proteins 0.000 description 10
- 241000700605 Viruses Species 0.000 description 10
- 150000003852 triazoles Chemical class 0.000 description 10
- 239000005089 Luciferase Substances 0.000 description 9
- 239000006227 byproduct Substances 0.000 description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 9
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 9
- JMIAPORGEDIDLT-UHFFFAOYSA-N ethyl ethanimidate Chemical compound CCOC(C)=N JMIAPORGEDIDLT-UHFFFAOYSA-N 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 9
- 230000008020 evaporation Effects 0.000 description 9
- SRVJKTDHMYAMHA-WUXMJOGZSA-N thioacetazone Chemical compound CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1 SRVJKTDHMYAMHA-WUXMJOGZSA-N 0.000 description 9
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 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
- 230000002829 reductive effect Effects 0.000 description 6
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 6
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 125000005392 carboxamide group Chemical group NC(=O)* 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 229910017604 nitric acid Inorganic materials 0.000 description 5
- 125000002971 oxazolyl group Chemical group 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000011593 sulfur Chemical group 0.000 description 5
- 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 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
- MEQBJJUWDCYIAB-UHFFFAOYSA-N 2-chloropyridin-3-amine Chemical compound NC1=CC=CN=C1Cl MEQBJJUWDCYIAB-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
- 108020004414 DNA Proteins 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000000908 ammonium hydroxide Substances 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 125000004122 cyclic group Chemical group 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
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 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
- 239000002243 precursor Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 229960002555 zidovudine Drugs 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
- VITIJXJNRKRDKF-UHFFFAOYSA-N 3-methyl-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound CC1=NNC(=S)N1C1=CC=CC=C1 VITIJXJNRKRDKF-UHFFFAOYSA-N 0.000 description 3
- MQFYUZCANYLWEI-UHFFFAOYSA-N 4-methylnaphthalen-1-amine Chemical compound C1=CC=C2C(C)=CC=C(N)C2=C1 MQFYUZCANYLWEI-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 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 3
- CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical group NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 150000002916 oxazoles Chemical class 0.000 description 3
- 125000003367 polycyclic group Chemical group 0.000 description 3
- 150000003254 radicals Chemical class 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
- 241001430294 unidentified retrovirus Species 0.000 description 3
- 230000029812 viral genome replication Effects 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- FBZVZUSVGKOWHG-UHFFFAOYSA-N 1,1-dimethoxy-n,n-dimethylethanamine Chemical compound COC(C)(OC)N(C)C FBZVZUSVGKOWHG-UHFFFAOYSA-N 0.000 description 2
- 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 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
- 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 2
- ZTRJVDUHNRWPAI-UHFFFAOYSA-N 2,4-dimethylnaphthalen-1-amine Chemical compound C1=CC=CC2=C(N)C(C)=CC(C)=C21 ZTRJVDUHNRWPAI-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
- MZKAXLQFMDDWBE-UHFFFAOYSA-N 2,5,7-trimethylquinolin-8-amine Chemical compound CC1=CC(C)=C(N)C2=NC(C)=CC=C21 MZKAXLQFMDDWBE-UHFFFAOYSA-N 0.000 description 2
- KUDYKIJCJSRIBX-UHFFFAOYSA-N 2,5,7-trimethylquinoline Chemical compound C1=CC(C)=NC2=CC(C)=CC(C)=C21 KUDYKIJCJSRIBX-UHFFFAOYSA-N 0.000 description 2
- 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 2
- LKRBLYAAKQMBSD-UHFFFAOYSA-N 2,5-dimethylquinolin-8-amine Chemical compound CC1=CC=C(N)C2=NC(C)=CC=C21 LKRBLYAAKQMBSD-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
- MKARNSWMMBGSHX-UHFFFAOYSA-N 3,5-dimethylaniline Chemical compound CC1=CC(C)=CC(N)=C1 MKARNSWMMBGSHX-UHFFFAOYSA-N 0.000 description 2
- TWQNFAMLCGTCCK-UHFFFAOYSA-N 3-methyl-4-(2,5,7-trimethylquinolin-8-yl)-1h-1,2,4-triazole-5-thione Chemical compound CC1=NN=C(S)N1C1=C(C)C=C(C)C2=CC=C(C)N=C12 TWQNFAMLCGTCCK-UHFFFAOYSA-N 0.000 description 2
- JUFWDGWACDXXGU-UHFFFAOYSA-N 3-methyl-4-(4-methyl-5,6,7,8-tetrahydronaphthalen-1-yl)-1h-1,2,4-triazole-5-thione Chemical compound CC1=NN=C(S)N1C1=CC=C(C)C2=C1CCCC2 JUFWDGWACDXXGU-UHFFFAOYSA-N 0.000 description 2
- JKRJVVWJUAWVCI-UHFFFAOYSA-N 3-methyl-4-(4-methylnaphthalen-1-yl)-1h-1,2,4-triazole-5-thione Chemical compound CC1=NN=C(S)N1C1=CC=C(C)C2=CC=CC=C12 JKRJVVWJUAWVCI-UHFFFAOYSA-N 0.000 description 2
- KYZYAPVNLSANPX-UHFFFAOYSA-N 4,5-dimethyl-3-(4-methylphenyl)-1h-imidazole-2-thione Chemical compound CC1=C(C)NC(=S)N1C1=CC=C(C)C=C1 KYZYAPVNLSANPX-UHFFFAOYSA-N 0.000 description 2
- CYEVFXOJJIMJGD-UHFFFAOYSA-N 4,7-dimethylnaphthalen-1-amine Chemical compound CC1=CC=C(N)C2=CC(C)=CC=C21 CYEVFXOJJIMJGD-UHFFFAOYSA-N 0.000 description 2
- FRKSWISVPLRSNU-UHFFFAOYSA-N 4-(2,4-dimethylnaphthalen-1-yl)-3-methyl-1h-1,2,4-triazole-5-thione Chemical compound CC1=NN=C(S)N1C1=C(C)C=C(C)C2=CC=CC=C12 FRKSWISVPLRSNU-UHFFFAOYSA-N 0.000 description 2
- ZTJIRSOFGIVFID-UHFFFAOYSA-N 4-(2,5-dimethylquinolin-8-yl)-3-methyl-1h-1,2,4-triazole-5-thione Chemical compound CC1=NN=C(S)N1C1=CC=C(C)C2=CC=C(C)N=C12 ZTJIRSOFGIVFID-UHFFFAOYSA-N 0.000 description 2
- OXLYBXGLTHLGAD-UHFFFAOYSA-N 4-(4,7-dimethylnaphthalen-1-yl)-3-methyl-1h-1,2,4-triazole-5-thione Chemical compound CC1=NN=C(S)N1C1=CC=C(C)C2=CC=C(C)C=C12 OXLYBXGLTHLGAD-UHFFFAOYSA-N 0.000 description 2
- NLKAAMWSLCZWPN-UHFFFAOYSA-N 4-(4-chloro-2-methoxy-5-methylquinolin-8-yl)-3-methyl-1h-1,2,4-triazole-5-thione Chemical compound C12=NC(OC)=CC(Cl)=C2C(C)=CC=C1N1C(C)=NN=C1S NLKAAMWSLCZWPN-UHFFFAOYSA-N 0.000 description 2
- CGWQTJSCBLYQSF-UHFFFAOYSA-N 4-(4-ethylnaphthalen-1-yl)-3-methyl-1h-1,2,4-triazole-5-thione Chemical compound C12=CC=CC=C2C(CC)=CC=C1N1C(C)=NN=C1S CGWQTJSCBLYQSF-UHFFFAOYSA-N 0.000 description 2
- JXBUVDXWYHVVJW-UHFFFAOYSA-N 4-[5-(dimethylamino)-2-methylquinolin-8-yl]-3-methyl-1h-1,2,4-triazole-5-thione Chemical compound C12=NC(C)=CC=C2C(N(C)C)=CC=C1N1C(C)=NN=C1S JXBUVDXWYHVVJW-UHFFFAOYSA-N 0.000 description 2
- URAIFJSZTAGYIG-UHFFFAOYSA-N 4-chloro-2-methoxy-5-methyl-8-nitroquinoline Chemical compound CC1=CC=C([N+]([O-])=O)C2=NC(OC)=CC(Cl)=C21 URAIFJSZTAGYIG-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
- ZQOMLDXMOIGYBI-UHFFFAOYSA-N 5-n,5-n,2-trimethylquinoline-5,8-diamine Chemical compound CC1=CC=C2C(N(C)C)=CC=C(N)C2=N1 ZQOMLDXMOIGYBI-UHFFFAOYSA-N 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
- QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 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
- 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
- 239000007832 Na2SO4 Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 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
- 229960004748 abacavir Drugs 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 150000003857 carboxamides Chemical class 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229960005319 delavirdine Drugs 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229960002656 didanosine 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
- 229960003804 efavirenz Drugs 0.000 description 2
- BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 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
- 229960001936 indinavir Drugs 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
- 229960001627 lamivudine Drugs 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 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
- FNUAOVLAPWPQET-UHFFFAOYSA-N n-(2-bromo-4-methylphenyl)-2-chloroacetamide Chemical compound CC1=CC=C(NC(=O)CCl)C(Br)=C1 FNUAOVLAPWPQET-UHFFFAOYSA-N 0.000 description 2
- CAZYIYRFWPLUPY-UHFFFAOYSA-N n-(2-bromophenyl)-2-[[4-(2,4-dimethylnaphthalen-1-yl)-5-methyl-1,2,4-triazol-3-yl]sulfanyl]acetamide Chemical compound CC=1C=C(C)C2=CC=CC=C2C=1N1C(C)=NN=C1SCC(=O)NC1=CC=CC=C1Br CAZYIYRFWPLUPY-UHFFFAOYSA-N 0.000 description 2
- FHWXHTWOJWDSAR-UHFFFAOYSA-N n-(2-bromophenyl)-2-chloroacetamide Chemical compound ClCC(=O)NC1=CC=CC=C1Br FHWXHTWOJWDSAR-UHFFFAOYSA-N 0.000 description 2
- COOUDGDPPWJPTO-UHFFFAOYSA-N n-(2-chloropyridin-3-yl)-2-[[4-(4-ethylnaphthalen-1-yl)-5-methyl-1,2,4-triazol-3-yl]sulfanyl]acetamide Chemical compound C12=CC=CC=C2C(CC)=CC=C1N1C(C)=NN=C1SCC(=O)NC1=CC=CN=C1Cl COOUDGDPPWJPTO-UHFFFAOYSA-N 0.000 description 2
- 229960000884 nelfinavir Drugs 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
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- RZXMPPFPUUCRFN-UHFFFAOYSA-N p-toluidine Chemical compound CC1=CC=C(N)C=C1 RZXMPPFPUUCRFN-UHFFFAOYSA-N 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- 239000008196 pharmacological composition Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 238000003757 reverse transcription PCR Methods 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 class 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 229960001203 stavudine Drugs 0.000 description 2
- 125000000565 sulfonamide group Chemical group 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- 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
- NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 1
- NXGHEDHQXXXTTP-UHFFFAOYSA-N 1,1-bis(methylsulfanyl)-2-nitroethene Chemical compound CSC(SC)=C[N+]([O-])=O NXGHEDHQXXXTTP-UHFFFAOYSA-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
- VQVBCZQTXSHJGF-UHFFFAOYSA-N 1-bromo-3-isocyanatobenzene Chemical compound BrC1=CC=CC(N=C=O)=C1 VQVBCZQTXSHJGF-UHFFFAOYSA-N 0.000 description 1
- WGMHMVLZFAJNOT-UHFFFAOYSA-N 1-ethoxyethylideneazanium;chloride Chemical compound [Cl-].CCOC(C)=[NH2+] WGMHMVLZFAJNOT-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
- MACMNSLOLFMQKL-UHFFFAOYSA-N 1-sulfanyltriazole Chemical compound SN1C=CN=N1 MACMNSLOLFMQKL-UHFFFAOYSA-N 0.000 description 1
- BBTYBONINZZLPA-UHFFFAOYSA-N 2,4-dichloro-5-methylquinoline Chemical compound ClC1=CC(Cl)=C2C(C)=CC=CC2=N1 BBTYBONINZZLPA-UHFFFAOYSA-N 0.000 description 1
- VSCRAZMECBNGMY-UHFFFAOYSA-N 2-[[4-(4-chloro-2-methoxy-5-methylquinolin-8-yl)-5-methyl-1,2,4-triazol-3-yl]sulfanyl]-n-(2-methyl-4-sulfamoylphenyl)acetamide Chemical compound C12=NC(OC)=CC(Cl)=C2C(C)=CC=C1N1C(C)=NN=C1SCC(=O)NC1=CC=C(S(N)(=O)=O)C=C1C VSCRAZMECBNGMY-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
- PRXNKTGXESJDAU-UHFFFAOYSA-N 3-(methoxymethyl)-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound COCC1=NNC(=S)N1C1=CC=CC=C1 PRXNKTGXESJDAU-UHFFFAOYSA-N 0.000 description 1
- VPLXBSKVKOEGBN-UHFFFAOYSA-N 3-[4-(dimethylamino)naphthalen-1-yl]-4-methyl-1h-imidazole-2-thione Chemical compound C12=CC=CC=C2C(N(C)C)=CC=C1N1C(C)=CN=C1S VPLXBSKVKOEGBN-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
- FRLUCKJPKRQSDG-UHFFFAOYSA-N 3-methyl-4-(4-methylphenyl)-5-(nitromethyl)-1,2,4-triazole Chemical compound CC1=NN=C(C[N+]([O-])=O)N1C1=CC=C(C)C=C1 FRLUCKJPKRQSDG-UHFFFAOYSA-N 0.000 description 1
- COTNURPTTGPEFA-UHFFFAOYSA-N 3-methyl-4-(4-methylphenyl)-5-nitro-1,2,4-triazole Chemical compound CC1=NN=C([N+]([O-])=O)N1C1=CC=C(C)C=C1 COTNURPTTGPEFA-UHFFFAOYSA-N 0.000 description 1
- CWDAPYZTJUQYAA-UHFFFAOYSA-N 3-methyl-5-methylsulfanyl-4-phenyl-1,2,4-triazole Chemical compound CSC1=NN=C(C)N1C1=CC=CC=C1 CWDAPYZTJUQYAA-UHFFFAOYSA-N 0.000 description 1
- JXGWJLRIPCOHMN-UHFFFAOYSA-N 3-oxobutan-2-ylcarbamic acid Chemical compound CC(=O)C(C)NC(O)=O JXGWJLRIPCOHMN-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
- LTZDTUJCHVBAGS-UHFFFAOYSA-N 4-chloro-2-methoxy-5-methylquinolin-8-amine Chemical compound CC1=CC=C(N)C2=NC(OC)=CC(Cl)=C21 LTZDTUJCHVBAGS-UHFFFAOYSA-N 0.000 description 1
- BCOWFSQIFGWBIR-UHFFFAOYSA-N 4-ethylnaphthalen-1-amine Chemical compound C1=CC=C2C(CC)=CC=C(N)C2=C1 BCOWFSQIFGWBIR-UHFFFAOYSA-N 0.000 description 1
- MNBOPSMHQDOJBK-UHFFFAOYSA-N 4-methyl-5,6,7,8-tetrahydronaphthalen-1-amine Chemical compound C1CCCC2=C1C(N)=CC=C2C MNBOPSMHQDOJBK-UHFFFAOYSA-N 0.000 description 1
- KKIGUVBJOHCXSP-UHFFFAOYSA-N 4-phenylthiosemicarbazide Chemical compound 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
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 108010041397 CD4 Antigens Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 102000009410 Chemokine receptor Human genes 0.000 description 1
- 108050000299 Chemokine receptor Proteins 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
- 206010010144 Completed suicide Diseases 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 108010032976 Enfuvirtide Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108090000331 Firefly luciferases 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
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 238000000719 MTS assay Methods 0.000 description 1
- 231100000070 MTS assay Toxicity 0.000 description 1
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methyl-N-phenylamine Natural products CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- DGPBLNPMRHRMRH-UHFFFAOYSA-N NC(=O)OCNS(=O)=O Chemical class NC(=O)OCNS(=O)=O DGPBLNPMRHRMRH-UHFFFAOYSA-N 0.000 description 1
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229910019213 POCl3 Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 241000711975 Vesicular stomatitis virus Species 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
- LXZKNCSZKIPEBS-UHFFFAOYSA-N [5-methyl-4-(4-methylphenyl)-1,2,4-triazol-3-yl]methanamine Chemical compound CC1=NN=C(CN)N1C1=CC=C(C)C=C1 LXZKNCSZKIPEBS-UHFFFAOYSA-N 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
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000005042 acyloxymethyl group Chemical group 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 230000008856 allosteric binding Effects 0.000 description 1
- 230000008850 allosteric inhibition Effects 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 230000000798 anti-retroviral effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940124522 antiretrovirals Drugs 0.000 description 1
- 239000003903 antiretrovirus agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 150000008366 benzophenones Chemical class 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 238000009640 blood culture Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000004970 cd4 cell Anatomy 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003067 chemokine receptor CCR5 antagonist Substances 0.000 description 1
- 125000000068 chlorophenyl group Chemical class 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 229940014461 combivir Drugs 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 150000008049 diazo compounds Chemical group 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- VDQVEACBQKUUSU-UHFFFAOYSA-M disodium;sulfanide Chemical compound [Na+].[Na+].[SH-] VDQVEACBQKUUSU-UHFFFAOYSA-M 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000009510 drug design 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
- 108700004025 env Genes Proteins 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- JLEKJZUYWFJPMB-UHFFFAOYSA-N ethyl 2-methoxyacetate Chemical compound CCOC(=O)COC JLEKJZUYWFJPMB-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
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000003574 free electron Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000004927 fusion Effects 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
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 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
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 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
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 230000028993 immune response 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
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000003010 ionic group Chemical group 0.000 description 1
- IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate Chemical compound [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 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
- 230000002503 metabolic effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- XMKNTAPBMSBGCL-UHFFFAOYSA-N n-(2-bromo-4-methylphenyl)-2-[(5-methyl-4-phenyl-1,2,4-triazol-3-yl)sulfanyl]acetamide Chemical compound C=1C=CC=CC=1N1C(C)=NN=C1SCC(=O)NC1=CC=C(C)C=C1Br XMKNTAPBMSBGCL-UHFFFAOYSA-N 0.000 description 1
- UYMUKYUFMXAXII-UHFFFAOYSA-N n-(2-bromophenyl)-2-[[5-methyl-4-(4-methylnaphthalen-1-yl)-1,2,4-triazol-3-yl]sulfanyl]acetamide Chemical compound C=1C=C(C)C2=CC=CC=C2C=1N1C(C)=NN=C1SCC(=O)NC1=CC=CC=C1Br UYMUKYUFMXAXII-UHFFFAOYSA-N 0.000 description 1
- QKVLCUMRZQZDCG-UHFFFAOYSA-N n-(2-chloro-4-sulfamoylphenyl)-2-[[4-(4,7-dimethylnaphthalen-1-yl)-5-methyl-1,2,4-triazol-3-yl]sulfanyl]acetamide Chemical compound C=1C=C(C)C2=CC=C(C)C=C2C=1N1C(C)=NN=C1SCC(=O)NC1=CC=C(S(N)(=O)=O)C=C1Cl QKVLCUMRZQZDCG-UHFFFAOYSA-N 0.000 description 1
- VKEDKCGEMMEAHQ-UHFFFAOYSA-N n-(2-chloropyridin-3-yl)-2-[[4-(2,5-dimethylquinolin-8-yl)-5-methyl-1,2,4-triazol-3-yl]sulfanyl]acetamide Chemical compound C=1C=C(C)C2=CC=C(C)N=C2C=1N1C(C)=NN=C1SCC(=O)NC1=CC=CN=C1Cl VKEDKCGEMMEAHQ-UHFFFAOYSA-N 0.000 description 1
- JONISSRTTMEVIQ-UHFFFAOYSA-N n-(2-chloropyridin-3-yl)-2-[[5-methyl-4-(4-methyl-5,6,7,8-tetrahydronaphthalen-1-yl)-1,2,4-triazol-3-yl]sulfanyl]acetamide Chemical compound C=1C=C(C)C=2CCCCC=2C=1N1C(C)=NN=C1SCC(=O)NC1=CC=CN=C1Cl JONISSRTTMEVIQ-UHFFFAOYSA-N 0.000 description 1
- LKYJAOJPAUQYHF-UHFFFAOYSA-N n-(2-methyl-4-sulfamoylphenyl)-2-[[5-methyl-4-(2,5,7-trimethylquinolin-8-yl)-1,2,4-triazol-3-yl]sulfanyl]acetamide Chemical compound CC=1C=C(C)C2=CC=C(C)N=C2C=1N1C(C)=NN=C1SCC(=O)NC1=CC=C(S(N)(=O)=O)C=C1C LKYJAOJPAUQYHF-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004524 naphthpyridyl group Chemical group C1(=CC=NC2=C1C1=CC=CC=C1C=C2)* 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000006959 non-competitive inhibition Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 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
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000001177 retroviral effect Effects 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
- 239000000523 sample Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 229940042055 systemic antimycotics triazole derivative Drugs 0.000 description 1
- 230000009885 systemic effect Effects 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
- NUAKKRMYBBXGFP-UHFFFAOYSA-N tert-butyl n-(3-oxobutan-2-yl)carbamate Chemical compound CC(=O)C(C)NC(=O)OC(C)(C)C NUAKKRMYBBXGFP-UHFFFAOYSA-N 0.000 description 1
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
- 229940021747 therapeutic vaccine Drugs 0.000 description 1
- 125000004149 thio group Chemical group *S* 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000002723 toxicity assay Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229940111527 trizivir Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000007502 viral entry Effects 0.000 description 1
- 230000006514 viral protein processing Effects 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)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- AIDS & HIV (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (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 |
|---|---|---|---|
| US0226816 | 2002-08-23 | ||
| USPCT/US02/26816 | 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 |
|---|---|
| CA2496565A1 CA2496565A1 (en) | 2004-04-15 |
| CA2496565C true CA2496565C (en) | 2013-04-02 |
Family
ID=32067653
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2496565A Expired - Fee Related CA2496565C (en) | 2002-08-23 | 2003-08-22 | Non-nucleoside reverse transcriptase inhibitors |
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 |
|---|---|---|---|---|
| EA009478B1 (ru) * | 2002-08-23 | 2008-02-28 | Ардеа Байосайенсиз, Инк. | Ненуклеозидные ингибиторы обратной транскриптазы |
| 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 |
| US7563905B2 (en) | 2004-03-12 | 2009-07-21 | 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 |
| ME01512B (me) * | 2004-08-25 | 2014-04-20 | Ardea Biosciences Inc | S-triazolil alfa-merkaptoacetanilida kao inhibitori HIV reversne transkriptaze |
| 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 |
| WO2008016522A2 (en) * | 2006-07-24 | 2008-02-07 | Gilead Sciences, Inc. | Hiv reverse transcriptase inhibitors |
| WO2009030996A1 (en) * | 2007-09-05 | 2009-03-12 | Coley Pharmaceutical Group, Inc. | Triazole compounds as toll-like receptor (tlr) agonists |
| BRPI0819847B1 (pt) | 2007-11-27 | 2022-01-11 | Ardea Biosciences, Inc | Compostos e composições |
| US8173690B2 (en) | 2008-09-04 | 2012-05-08 | Ardea Biosciences, Inc. | Compounds, compositions and methods of using same for modulating uric acid levels |
| CN102186832B (zh) | 2008-09-04 | 2014-04-02 | 亚德生化公司 | 调节尿酸含量的化合物、组合物及其使用方法 |
| US8242154B2 (en) | 2008-09-04 | 2012-08-14 | Ardea Biosciences, Inc. | Compounds, compositions and methods of using same for modulating uric acid levels |
| 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 |
| CN103140474A (zh) * | 2010-07-02 | 2013-06-05 | 吉里德科学公司 | 治疗aids的萘-2-基乙酸衍生物 |
| 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 |
| CN105394046B (zh) | 2010-10-25 | 2019-03-01 | 范德比尔特大学 | 用于抑制昆虫宿主感觉的组合物 |
| CA2835328C (en) | 2011-05-06 | 2019-10-15 | Vanderbilt University | Compositions 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 |
| CN107529746B (zh) | 2015-03-25 | 2021-09-07 | 范德比尔特大学 | 作为orco介导的气味感觉干扰剂的二元组合物 |
| MA42145B1 (fr) | 2015-05-20 | 2020-05-29 | Amgen Inc | Triazoles agonistes du récepteur apj |
| EP3452466B1 (en) | 2016-05-03 | 2020-08-12 | Amgen Inc. | Heterocyclic triazole compounds as agonists of the apj receptor |
| EP3541803B1 (en) | 2016-11-16 | 2020-12-23 | Amgen Inc. | Triazole pyridyl compounds as agonists of the apj receptor |
| EP3541802B1 (en) | 2016-11-16 | 2025-01-01 | Amgen Inc. | Alkyl substituted 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 |
| WO2018093577A1 (en) | 2016-11-16 | 2018-05-24 | Amgen Inc. | Cycloalkyl substituted triazole 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 |
| US11046680B1 (en) | 2016-11-16 | 2021-06-29 | Amgen Inc. | Heteroaryl-substituted triazoles as APJ receptor agonists |
| WO2019089335A1 (en) | 2017-11-03 | 2019-05-09 | Amgen Inc. | Fused triazole agonists of the apj receptor |
| EP3788037A1 (en) | 2018-05-01 | 2021-03-10 | 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 |
| WO1998035957A1 (en) | 1997-02-14 | 1998-08-20 | Bayer Corporation | Amide derivatives as selective neuropeptide y receptor antagonists |
| US6245817B1 (en) * | 1997-02-14 | 2001-06-12 | Bayer Corporation | NPY5 receptor antagonists and methods for using same |
| BRPI9909191B8 (pt) * | 1998-03-27 | 2021-07-06 | Janssen Pharmaceutica Nv | derivados de pirimidina inibidores do hiv, seu uso e composição farmacêutica que os compreende |
| US6414147B1 (en) * | 1998-12-23 | 2002-07-02 | 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 |
| CZ20032366A3 (en) | 2001-03-02 | 2004-04-14 | Smithkline Beecham Corporation | Benzophenones as inhibitors of reverse transcriptase |
| EA009478B1 (ru) * | 2002-08-23 | 2008-02-28 | Ардеа Байосайенсиз, Инк. | Ненуклеозидные ингибиторы обратной транскриптазы |
| 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 |
| AU2007237901B2 (en) * | 2006-04-18 | 2012-07-05 | Ardea Biosciences, Inc. | Pyridone sulfonamides and pyridone sulfamides as MEK inhibitors |
| EP2132211A4 (en) * | 2006-11-09 | 2011-12-07 | Ardea Biosciences Inc | 4-CYANPHENYLAMINO-SUBSTITUTED BICYCLIC AND HETEROCYCLIC COMPOUNDS AS AN HIV HEMMER |
-
2003
- 2003-08-22 EA EA200500399A patent/EA009478B1/ru not_active IP Right Cessation
- 2003-08-22 EP EP03786506A patent/EP1545483B1/en not_active Expired - Lifetime
- 2003-08-22 AU AU2003295324A patent/AU2003295324B2/en not_active Ceased
- 2003-08-22 US US10/526,249 patent/US20060135556A1/en not_active Abandoned
- 2003-08-22 JP JP2004541500A patent/JP4413781B2/ja not_active Expired - Fee Related
- 2003-08-22 DE DE60336664T patent/DE60336664D1/de not_active Expired - Lifetime
- 2003-08-22 CA CA2496565A patent/CA2496565C/en not_active Expired - Fee Related
- 2003-08-22 EP EP11160994A patent/EP2353593B1/en not_active Expired - Lifetime
- 2003-08-22 BR BR0313747-3A patent/BR0313747A/pt not_active Application Discontinuation
- 2003-08-22 CN CN038243377A patent/CN1697650B/zh not_active Expired - Fee Related
- 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 WO PCT/US2003/027433 patent/WO2004030611A2/en not_active Ceased
-
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
Also Published As
| Publication number | Publication date |
|---|---|
| EP1545483A2 (en) | 2005-06-29 |
| DE60336664D1 (de) | 2011-05-19 |
| US20060135556A1 (en) | 2006-06-22 |
| EP2353593B1 (en) | 2012-08-22 |
| BR0313747A (pt) | 2005-06-21 |
| ZA200502384B (en) | 2007-03-28 |
| AU2008246249A1 (en) | 2008-12-11 |
| WO2004030611A3 (en) | 2004-06-17 |
| JP2006505543A (ja) | 2006-02-16 |
| JP4413781B2 (ja) | 2010-02-10 |
| WO2004030611A2 (en) | 2004-04-15 |
| AU2008246249B2 (en) | 2010-09-30 |
| HK1085667A1 (en) | 2006-09-01 |
| EP1545483A4 (en) | 2009-03-25 |
| CN1697650A (zh) | 2005-11-16 |
| AU2003295324B2 (en) | 2008-08-28 |
| EA009478B1 (ru) | 2008-02-28 |
| MXPA05002070A (es) | 2005-07-05 |
| EP1545483B1 (en) | 2011-04-06 |
| AU2003295324A1 (en) | 2004-04-23 |
| CN1697650B (zh) | 2010-11-10 |
| EP2353593A1 (en) | 2011-08-10 |
| ATE504294T1 (de) | 2011-04-15 |
| US20080249131A1 (en) | 2008-10-09 |
| CA2496565A1 (en) | 2004-04-15 |
| EA200500399A1 (ru) | 2005-12-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2008246249B2 (en) | Non-nucleoside reverse transcriptase inhibitors | |
| ES2380604T3 (es) | S-triazolil alfa-mercaptoacetanilidas como inhibidores de la transcriptasa inversa del VIH | |
| Song et al. | Discovery of novel pyridazinylthioacetamides as potent HIV-1 NNRTIs using a structure-based bioisosterism approach | |
| HK1085667B (en) | Non-nucleoside reverse transcriptase inhibitors | |
| EP1210336B1 (en) | Substituted benzimidazoles as non-nucleoside inhibitors of reverse transcriptase | |
| KR20090111357A (ko) | ＨＩＶ 역 전사 효소의 억제제로서 Ｓ-트리아졸릴 α-메르캅토아세트아닐리드 | |
| HK1167823A (en) | Triazolyl alpha -mercaptoacetanildes as inhibitors of hiv reverse transcriptase |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20210823 |