JP4413781B2 - 非ヌクレオシド逆転写酵素インヒビター - Google Patents
非ヌクレオシド逆転写酵素インヒビター Download PDFInfo
- Publication number
- JP4413781B2 JP4413781B2 JP2004541500A JP2004541500A JP4413781B2 JP 4413781 B2 JP4413781 B2 JP 4413781B2 JP 2004541500 A JP2004541500 A JP 2004541500A JP 2004541500 A JP2004541500 A JP 2004541500A JP 4413781 B2 JP4413781 B2 JP 4413781B2
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- substituted
- mmol
- methyl
- phenyl
- 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 4
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 132
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 65
- 125000000623 heterocyclic group Chemical group 0.000 claims description 64
- 239000001257 hydrogen Substances 0.000 claims description 52
- 229910052739 hydrogen Inorganic materials 0.000 claims description 52
- -1 monosubstituted phenyl Chemical group 0.000 claims description 52
- 125000003118 aryl group Chemical group 0.000 claims description 48
- 229910052736 halogen Inorganic materials 0.000 claims description 43
- 150000002367 halogens Chemical class 0.000 claims description 43
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 39
- 125000001424 substituent group Chemical group 0.000 claims description 33
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000003107 substituted aryl group Chemical group 0.000 claims description 12
- 125000002252 acyl group Chemical group 0.000 claims description 10
- 150000003248 quinolines Chemical class 0.000 claims description 10
- 125000001624 naphthyl group Chemical group 0.000 claims description 9
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
- 125000005257 alkyl acyl group Chemical group 0.000 claims description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 abstract description 46
- 239000002777 nucleoside Substances 0.000 abstract description 21
- 150000003833 nucleoside derivatives Chemical class 0.000 abstract description 20
- 239000003112 inhibitor Substances 0.000 abstract description 17
- 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
- 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
- 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 71
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- 239000000203 mixture Substances 0.000 description 62
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- 102100034349 Integrase Human genes 0.000 description 46
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 46
- 125000004429 atom Chemical group 0.000 description 43
- 239000000243 solution Substances 0.000 description 43
- 239000002904 solvent Substances 0.000 description 36
- 238000000034 method Methods 0.000 description 35
- 125000005647 linker group Chemical group 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- 229910052717 sulfur Inorganic materials 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- 125000003342 alkenyl group Chemical group 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 125000000304 alkynyl group Chemical group 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- 229910052760 oxygen Inorganic materials 0.000 description 23
- 239000007787 solid Substances 0.000 description 23
- 239000008346 aqueous phase Substances 0.000 description 22
- 241000725303 Human immunodeficiency virus Species 0.000 description 20
- 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
- 239000012044 organic layer Substances 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
- 229910052938 sodium sulfate Inorganic materials 0.000 description 17
- 235000011152 sodium sulphate Nutrition 0.000 description 17
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 125000005842 heteroatom Chemical group 0.000 description 15
- 230000005764 inhibitory process Effects 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 125000000753 cycloalkyl group Chemical group 0.000 description 14
- 230000002401 inhibitory effect Effects 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- 230000003612 virological effect Effects 0.000 description 14
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 12
- 125000000392 cycloalkenyl group Chemical group 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 125000001072 heteroaryl group Chemical group 0.000 description 11
- 239000000651 prodrug Substances 0.000 description 11
- 229940002612 prodrug Drugs 0.000 description 11
- 150000003852 triazoles Chemical class 0.000 description 11
- 208000031886 HIV Infections Diseases 0.000 description 10
- 108060001084 Luciferase Proteins 0.000 description 10
- 150000002460 imidazoles Chemical class 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000005089 Luciferase Substances 0.000 description 9
- 241000700605 Viruses Species 0.000 description 9
- 239000006227 byproduct Substances 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- JMIAPORGEDIDLT-UHFFFAOYSA-N ethyl ethanimidate Chemical compound CCOC(C)=N JMIAPORGEDIDLT-UHFFFAOYSA-N 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- SRVJKTDHMYAMHA-WUXMJOGZSA-N thioacetazone Chemical compound CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1 SRVJKTDHMYAMHA-WUXMJOGZSA-N 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 6
- 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
- 229910052799 carbon Inorganic materials 0.000 description 6
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
- 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 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 125000005392 carboxamide group Chemical group NC(=O)* 0.000 description 5
- 208000015181 infectious disease Diseases 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
- 239000011734 sodium Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000011593 sulfur Chemical group 0.000 description 5
- 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
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 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
- 239000002253 acid Substances 0.000 description 4
- 239000000908 ammonium hydroxide Substances 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
- 238000009472 formulation Methods 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
- 229910017604 nitric acid Inorganic materials 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 239000000126 substance Substances 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
- 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 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
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 3
- 101710149870 C-C chemokine receptor type 5 Proteins 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
- 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
- 125000004414 alkyl thio group Chemical group 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 125000004104 aryloxy group Chemical group 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000002585 base Substances 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
- 230000014509 gene expression Effects 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 239000005457 ice water Substances 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
- 125000003367 polycyclic group Chemical group 0.000 description 3
- 230000009467 reduction Effects 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
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 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 3
- 150000003573 thiols Chemical class 0.000 description 3
- 125000005425 toluyl group Chemical group 0.000 description 3
- 230000029812 viral genome replication Effects 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- 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
- ABQKHKWXTUVKGF-UHFFFAOYSA-N 1-isothiocyanato-4-methylbenzene Chemical compound CC1=CC=C(N=C=S)C=C1 ABQKHKWXTUVKGF-UHFFFAOYSA-N 0.000 description 2
- 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 2
- QPUYECUOLPXSFR-UHFFFAOYSA-N 1-methylnaphthalene Chemical compound C1=CC=C2C(C)=CC=CC2=C1 QPUYECUOLPXSFR-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
- 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
- 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 2
- 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 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
- 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
- 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 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
- 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 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
- KKIGUVBJOHCXSP-UHFFFAOYSA-N 4-phenylthiosemicarbazide Chemical compound NNC(=S)NC1=CC=CC=C1 KKIGUVBJOHCXSP-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 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
- 0 Cc1cnc(*)[n]1-c(c1ccccc11)ccc1N(C)C Chemical compound Cc1cnc(*)[n]1-c(c1ccccc11)ccc1N(C)C 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
- 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
- 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
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 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 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
- 230000002378 acidificating effect Effects 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000000798 anti-retroviral effect Effects 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 150000003857 carboxamides Chemical class 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 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
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
- 239000002552 dosage form Substances 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
- 230000008020 evaporation Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 125000004446 heteroarylalkyl group Chemical group 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
- 238000000691 measurement method Methods 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
- FHWXHTWOJWDSAR-UHFFFAOYSA-N n-(2-bromophenyl)-2-chloroacetamide Chemical compound ClCC(=O)NC1=CC=CC=C1Br FHWXHTWOJWDSAR-UHFFFAOYSA-N 0.000 description 2
- JNLKQVABMYMPEE-UHFFFAOYSA-N n-(2-chloropyridin-3-yl)-2-[[4-[5-(dimethylamino)-2-methylquinolin-8-yl]-5-methyl-1,2,4-triazol-3-yl]sulfanyl]acetamide Chemical compound C12=NC(C)=CC=C2C(N(C)C)=CC=C1N1C(C)=NN=C1SCC(=O)NC1=CC=CN=C1Cl JNLKQVABMYMPEE-UHFFFAOYSA-N 0.000 description 2
- 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 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
- 210000000056 organ Anatomy 0.000 description 2
- 150000002916 oxazoles Chemical class 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
- 239000008196 pharmacological composition Substances 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
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- 238000010839 reverse transcription Methods 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 group 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 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
- 125000000565 sulfonamide group Chemical group 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 229920002554 vinyl polymer Polymers 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
- NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 1
- JTVIRZXORWVLBQ-UHFFFAOYSA-N 1,1-bis(methylsulfanyl)-2-nitroethane Chemical compound CSC(SC)C[N+]([O-])=O JTVIRZXORWVLBQ-UHFFFAOYSA-N 0.000 description 1
- FBZVZUSVGKOWHG-UHFFFAOYSA-N 1,1-dimethoxy-n,n-dimethylethanamine Chemical compound COC(C)(OC)N(C)C FBZVZUSVGKOWHG-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
- 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
- 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
- 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 1
- ZMXIYERNXPIYFR-UHFFFAOYSA-N 1-ethylnaphthalene Chemical compound C1=CC=C2C(CC)=CC=CC2=C1 ZMXIYERNXPIYFR-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
- 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
- KUDYKIJCJSRIBX-UHFFFAOYSA-N 2,5,7-trimethylquinoline Chemical compound C1=CC(C)=NC2=CC(C)=CC(C)=C21 KUDYKIJCJSRIBX-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
- 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
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 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
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 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
- 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 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
- 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
- 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 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
- 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 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
- 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 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound 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
- QKVLCUMRZQZDCG-UHFFFAOYSA-N Cc([n]1-c2ccc(C)c3ccc(C)cc23)nnc1SCC(Nc(ccc(S(N)(=O)=O)c1)c1Cl)=O Chemical compound Cc([n]1-c2ccc(C)c3ccc(C)cc23)nnc1SCC(Nc(ccc(S(N)(=O)=O)c1)c1Cl)=O QKVLCUMRZQZDCG-UHFFFAOYSA-N 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
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 108010032976 Enfuvirtide 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
- 241000282412 Homo Species 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
- MUFRWHVKUCJNRW-UHFFFAOYSA-N N,N-diethyl-2-methyl-8-nitroquinolin-5-amine Chemical compound CCN(CC)C1=C2C=CC(=NC2=C(C=C1)[N+](=O)[O-])C MUFRWHVKUCJNRW-UHFFFAOYSA-N 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
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010034133 Pathogen resistance Diseases 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 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
- 208000036142 Viral infection Diseases 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
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000005042 acyloxymethyl group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 239000005557 antagonist Substances 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
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 150000007514 bases Chemical class 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
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 238000009640 blood culture Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 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
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 1
- 125000000068 chlorophenyl group 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
- 230000007812 deficiency Effects 0.000 description 1
- 150000008049 diazo compounds Chemical group 0.000 description 1
- 229960002656 didanosine Drugs 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
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 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
- 239000000706 filtrate Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 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
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000009931 harmful effect Effects 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
- 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
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000028993 immune response Effects 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
- 230000004898 mitochondrial function Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 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 1
- WMGKLISYGAEUKW-UHFFFAOYSA-N n-(2-bromophenyl)-2-[4,5-dimethyl-1-(4-methylphenyl)imidazol-2-yl]sulfanylacetamide Chemical compound C=1C=C(C)C=CC=1N1C(C)=C(C)N=C1SCC(=O)NC1=CC=CC=C1Br WMGKLISYGAEUKW-UHFFFAOYSA-N 0.000 description 1
- 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 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
- CXUZUVOHOXUPFK-UHFFFAOYSA-N n-(2-chlorophenyl)-2-[[5-(methoxymethyl)-4-phenyl-1,2,4-triazol-3-yl]sulfanyl]acetamide Chemical compound C=1C=CC=CC=1N1C(COC)=NN=C1SCC(=O)NC1=CC=CC=C1Cl CXUZUVOHOXUPFK-UHFFFAOYSA-N 0.000 description 1
- PJRKRMNOOYDSEG-UHFFFAOYSA-N n-(2-chloropyridin-3-yl)-2-[1-[4-(dimethylamino)naphthalen-1-yl]-5-methylimidazol-2-yl]sulfanylacetamide Chemical compound C12=CC=CC=C2C(N(C)C)=CC=C1N1C(C)=CN=C1SCC(=O)NC1=CC=CN=C1Cl PJRKRMNOOYDSEG-UHFFFAOYSA-N 0.000 description 1
- 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 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
- 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
- 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
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 238000005457 optimization Methods 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
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000005561 phenanthryl group Chemical group 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
- 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
- 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
- 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
- 239000012265 solid product Substances 0.000 description 1
- 229960001203 stavudine Drugs 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 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
- PWQIGBOSLQHOBT-SSDOTTSWSA-N tert-butyl n-[(2r)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl]carbamate Chemical compound CON(C)C(=O)[C@@H](C)NC(=O)OC(C)(C)C PWQIGBOSLQHOBT-SSDOTTSWSA-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
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000002723 toxicity assay Methods 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
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 231100000925 very toxic Toxicity 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)
- 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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US0226816 | 2002-08-23 | ||
| PCT/US2003/027433 WO2004030611A2 (en) | 2002-08-23 | 2003-08-22 | Non-nucleoside reverse transcriptase inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2006505543A JP2006505543A (ja) | 2006-02-16 |
| JP2006505543A5 JP2006505543A5 (enExample) | 2006-04-06 |
| JP4413781B2 true JP4413781B2 (ja) | 2010-02-10 |
Family
ID=32067653
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004541500A Expired - Fee Related JP4413781B2 (ja) | 2002-08-23 | 2003-08-22 | 非ヌクレオシド逆転写酵素インヒビター |
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
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 |
| 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 |
| CN1697650B (zh) | 2010-11-10 |
| 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 |
|---|---|---|
| JP4413781B2 (ja) | 非ヌクレオシド逆転写酵素インヒビター | |
| JP4952943B2 (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 | |
| Taha et al. | Molecular hybridization conceded exceptionally potent quinolinyl-oxadiazole hybrids through phenyl linked thiosemicarbazide antileishmanial scaffolds: In silico validation and SAR studies | |
| US8501767B2 (en) | Imidazopyridines and imidazopyrimidines as HIV-1 reverse transcriptase inhibitors | |
| Arnaiz et al. | Synthesis of anionic carbosilane dendrimers via “click chemistry” and their antiviral properties against HIV | |
| US20160263231A1 (en) | Methods and Compositions Related to Viral Inhibition | |
| JP5576853B2 (ja) | 置換（ピラゾリルカルボニル）イミダゾリジノンおよびその使用 | |
| US11136301B2 (en) | Broad spectrum antiviral compounds and uses thereof | |
| TW201412720A (zh) | 三（雜）芳基吡唑及其應用 | |
| 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 | |
| KR100940058B1 (ko) | ＨＩＶ 역 전사 효소의 억제제로서 Ｓ-트리아졸릴 α-메르캅토아세트아닐리드 | |
| WO2007074871A1 (ja) | 新規ｃｘｃｒ４拮抗剤及びその用途 | |
| KR20000053122A (ko) | Ｈｉｖ 프로테아제 억제제로 유용한 1-(3-아미노인다졸-5-일)-3-페닐메틸-시클릭 우레아 | |
| EP1381360A1 (en) | Compounds and methods for inhibiting metap2 in mammals | |
| HK1167823A (en) | Triazolyl alpha -mercaptoacetanildes as inhibitors of hiv reverse transcriptase |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20051114 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20051114 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20071130 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20071130 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090609 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090909 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20091020 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20091118 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121127 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 4413781 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20131127 Year of fee payment: 4 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |