ES2619960T3 - Inhibidores de la replicación del virus de la inmunodeficiencia humana - Google Patents
Inhibidores de la replicación del virus de la inmunodeficiencia humana Download PDFInfo
- Publication number
- ES2619960T3 ES2619960T3 ES13750479.1T ES13750479T ES2619960T3 ES 2619960 T3 ES2619960 T3 ES 2619960T3 ES 13750479 T ES13750479 T ES 13750479T ES 2619960 T3 ES2619960 T3 ES 2619960T3
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- Prior art keywords
- tert
- butoxy
- acetic
- dioxa
- acid
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title claims description 51
- 241000725303 Human immunodeficiency virus Species 0.000 title description 39
- 230000029812 viral genome replication Effects 0.000 title description 2
- -1 homopiperidinyl Chemical group 0.000 claims abstract description 181
- 150000001875 compounds Chemical class 0.000 claims abstract description 130
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 69
- 150000003839 salts Chemical class 0.000 claims abstract description 53
- 125000001475 halogen functional group Chemical group 0.000 claims abstract description 35
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 33
- 239000001257 hydrogen Substances 0.000 claims abstract description 33
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 30
- 125000001424 substituent group Chemical group 0.000 claims abstract description 30
- 125000004438 haloalkoxy group Chemical group 0.000 claims abstract description 28
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 28
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 24
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 15
- 125000004450 alkenylene group Chemical group 0.000 claims abstract description 14
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 14
- 125000005434 dihydrobenzoxazinyl group Chemical group O1N(CCC2=C1C=CC=C2)* 0.000 claims abstract description 10
- 125000002393 azetidinyl group Chemical group 0.000 claims abstract description 8
- 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 8
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 8
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 8
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 7
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims abstract description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims abstract description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims abstract description 5
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000002009 alkene group Chemical group 0.000 claims abstract description 3
- 235000019256 formaldehyde Nutrition 0.000 claims abstract description 3
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 465
- 239000000203 mixture Substances 0.000 claims description 239
- 239000002253 acid Substances 0.000 claims description 122
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- 239000003795 chemical substances by application Substances 0.000 claims description 39
- 208000031886 HIV Infections Diseases 0.000 claims description 32
- 208000037357 HIV infectious disease Diseases 0.000 claims description 32
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 32
- 239000003814 drug Substances 0.000 claims description 22
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- 239000002777 nucleoside Substances 0.000 claims description 12
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- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims description 9
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims description 9
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- 108010078851 HIV Reverse Transcriptase Proteins 0.000 claims description 9
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims description 9
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- 230000008878 coupling Effects 0.000 claims description 8
- 238000010168 coupling process Methods 0.000 claims description 8
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
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- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 6
- 229940099797 HIV integrase inhibitor Drugs 0.000 claims description 5
- 239000003084 hiv integrase inhibitor Substances 0.000 claims description 5
- HQLILHPGWSURBT-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxy]acetic acid Chemical compound CC(C)(C)OCC(O)=O HQLILHPGWSURBT-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
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- 235000019439 ethyl acetate Nutrition 0.000 description 190
- 239000000243 solution Substances 0.000 description 161
- 125000005336 allyloxy group Chemical group 0.000 description 160
- 238000006243 chemical reaction Methods 0.000 description 154
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- RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 description 109
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 86
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 72
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 70
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 60
- 239000003921 oil Substances 0.000 description 60
- 235000019198 oils Nutrition 0.000 description 60
- 239000012074 organic phase Substances 0.000 description 57
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 52
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
- 239000011541 reaction mixture Substances 0.000 description 47
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 46
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 44
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 43
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 43
- 235000019341 magnesium sulphate Nutrition 0.000 description 43
- 238000002953 preparative HPLC Methods 0.000 description 43
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 41
- 239000012267 brine Substances 0.000 description 40
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 40
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 38
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 35
- 239000012071 phase Substances 0.000 description 34
- 230000002829 reductive effect Effects 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
- 229910000029 sodium carbonate Inorganic materials 0.000 description 31
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
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- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 28
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- 238000003756 stirring Methods 0.000 description 24
- ZRPFJAPZDXQHSM-UHFFFAOYSA-L 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazole;dichloro-[(2-propan-2-yloxyphenyl)methylidene]ruthenium Chemical compound CC(C)OC1=CC=CC=C1C=[Ru](Cl)(Cl)=C1N(C=2C(=CC(C)=CC=2C)C)CCN1C1=C(C)C=C(C)C=C1C ZRPFJAPZDXQHSM-UHFFFAOYSA-L 0.000 description 22
- 229910052757 nitrogen Inorganic materials 0.000 description 20
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
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- 239000011368 organic material Substances 0.000 description 6
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- XGOONJGQNKCWLR-UHFFFAOYSA-N 4-methyl-4-prop-2-enoxypiperidine Chemical compound C=CCOC1(C)CCNCC1 XGOONJGQNKCWLR-UHFFFAOYSA-N 0.000 description 5
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- 239000008346 aqueous phase Substances 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
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- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 4
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- 229960000838 tipranavir Drugs 0.000 description 1
- SUJUHGSWHZTSEU-FYBSXPHGSA-N tipranavir Chemical compound C([C@@]1(CCC)OC(=O)C([C@H](CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)=C(O)C1)CC1=CC=CC=C1 SUJUHGSWHZTSEU-FYBSXPHGSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 238000001946 ultra-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
Classifications
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- 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
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed systems contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/16—Peri-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/16—Peri-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (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)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (7)
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| US201261683772P | 2012-08-16 | 2012-08-16 | |
| US201261683772P | 2012-08-16 | ||
| US201361818572P | 2013-05-02 | 2013-05-02 | |
| US201361818572P | 2013-05-02 | ||
| US201313959268 | 2013-08-05 | ||
| US13/959,268 US8906929B2 (en) | 2012-08-16 | 2013-08-05 | Inhibitors of human immunodeficiency virus replication |
| PCT/US2013/054532 WO2014028384A1 (en) | 2012-08-16 | 2013-08-12 | Inhibitors of human immunodeficiency virus replication |
Publications (1)
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| ES2619960T3 true ES2619960T3 (es) | 2017-06-27 |
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| EP (1) | EP2888266B1 (enExample) |
| JP (1) | JP6214657B2 (enExample) |
| KR (1) | KR20150042830A (enExample) |
| CN (1) | CN104583214B (enExample) |
| AU (1) | AU2013302873B2 (enExample) |
| BR (1) | BR112015003175A2 (enExample) |
| CA (1) | CA2882077A1 (enExample) |
| EA (1) | EA201590358A1 (enExample) |
| ES (1) | ES2619960T3 (enExample) |
| IL (1) | IL237154A (enExample) |
| MX (1) | MX2015001899A (enExample) |
| SG (1) | SG11201500887QA (enExample) |
| TW (1) | TW201412750A (enExample) |
| WO (1) | WO2014028384A1 (enExample) |
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| AU2011274322B2 (en) | 2010-07-02 | 2015-08-13 | Gilead Sciences, Inc. | Naphth- 2 -ylacetic acid derivatives to treat AIDS |
| BR112012033689A2 (pt) | 2010-07-02 | 2019-09-24 | Gilead Sciences Inc | derivados de ácido 2-quinolinil-acético como compostos de hiv antivirais |
| EA024952B1 (ru) | 2011-04-21 | 2016-11-30 | Джилид Сайэнс, Инк. | Бензотиазолы и их применение для лечения вич-инфекции |
| US9284323B2 (en) | 2012-01-04 | 2016-03-15 | Gilead Sciences, Inc. | Naphthalene acetic acid derivatives against HIV infection |
| WO2013103724A1 (en) | 2012-01-04 | 2013-07-11 | Gilead Sciences, Inc. | 2- (tert - butoxy) -2- (7 -methylquinolin- 6 - yl) acetic acid derivatives for treating aids |
| ES2668422T3 (es) | 2012-04-20 | 2018-05-18 | Gilead Sciences, Inc. | Derivados del ácido benzotiazol-6-il acético y su uso para tratar una infección por VIH |
| US8906929B2 (en) | 2012-08-16 | 2014-12-09 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| EP2970301B1 (en) * | 2013-03-13 | 2017-01-11 | VIIV Healthcare UK (No.5) Limited | Inhibitors of human immunodeficiency virus replication |
| US9540393B2 (en) | 2013-03-14 | 2017-01-10 | VIIV Healthcare UK (No.5) Limited | Inhibitors of human immunodeficiency virus replication |
| US9944656B2 (en) | 2014-02-12 | 2018-04-17 | VIIV Healthcare UK (No.5) Limited | Benzothiazole macrocycles as inhibitors of human immunodeficiency virus replication |
| WO2015123182A1 (en) * | 2014-02-12 | 2015-08-20 | Bristol-Myers Squibb Company | Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication |
| WO2015126758A1 (en) * | 2014-02-18 | 2015-08-27 | Bristol-Myers Squibb Company | Imidazopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication |
| US9834566B2 (en) * | 2014-02-18 | 2017-12-05 | VIIV Healthcare UK (No.5) Limited | Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication |
| US9409922B2 (en) * | 2014-02-18 | 2016-08-09 | Bristol-Myers Squibb Company | Imidazopyridine macrocycles as inhibitors of human immunodeficiency virus replication |
| US9273067B2 (en) | 2014-02-19 | 2016-03-01 | Bristol-Myers Squibb Company | Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication |
| EP3107913B1 (en) | 2014-02-19 | 2018-07-04 | VIIV Healthcare UK (No.5) Limited | Inhibitors of human immunodeficiency virus replication |
| US10125148B2 (en) * | 2014-02-19 | 2018-11-13 | Viiv Healthcare Uk (No. 5) Limited | Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication |
| US9637501B2 (en) | 2014-02-20 | 2017-05-02 | Viiv Healthcare Uk (No. 5) Limited | Pyridin-3-yl acetic acid macrocycles as inhibitors of human immunodeficiency virus replication |
| JP6579549B2 (ja) * | 2014-05-16 | 2019-09-25 | 塩野義製薬株式会社 | Ｈｉｖ複製阻害作用を有する３環性複素環誘導体 |
| WO2016194806A1 (ja) | 2015-05-29 | 2016-12-08 | 塩野義製薬株式会社 | Ｈｉｖ複製阻害作用を有する含窒素３環性誘導体 |
| CA2994517A1 (en) * | 2015-08-10 | 2017-02-16 | VIIV Healthcare UK (No.5) Limited | Imidazopyridine macrocycles as inhibitors of human immunodeficiency virus replication |
| EP3606921B1 (en) | 2017-04-06 | 2022-06-01 | Inventiva | New compounds inhibitors of the yap/taz-tead interaction and their use in the treatment of malignant mesothelioma. |
| EP3632908A1 (en) | 2018-10-02 | 2020-04-08 | Inventiva | Inhibitors of the yap/taz-tead interaction and their use in the treatment of cancer |
| CN113874079B (zh) | 2019-03-22 | 2024-11-08 | 吉利德科学公司 | 桥连三环氨基甲酰基吡啶酮化合物及其药学用途 |
| EP4110783A1 (en) | 2020-02-24 | 2023-01-04 | Gilead Sciences, Inc. | Tetracyclic compounds for treating hiv infection |
| WO2022072520A1 (en) | 2020-09-30 | 2022-04-07 | Gilead Sciences, Inc. | Bridged tricyclic carbamoylpyridone compounds and uses thereof |
| DK4196479T5 (da) | 2021-01-19 | 2025-01-02 | Gilead Sciences Inc | Substituerede pyridotriazinforbindelser og anvendelser deraf |
| TWI843506B (zh) | 2022-04-06 | 2024-05-21 | 美商基利科學股份有限公司 | 橋聯三環胺甲醯基吡啶酮化合物及其用途 |
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| GB427857A (en) | 1934-08-02 | 1935-05-01 | Newsum Sons & Company Ltd H | A new or improved system of construction for skeleton structures, particularly vehicle body frames and door frames |
| US7939545B2 (en) | 2006-05-16 | 2011-05-10 | Boehringer Ingelheim International Gmbh | Inhibitors of human immunodeficiency virus replication |
| CA2705312C (en) * | 2007-11-15 | 2013-06-25 | Boehringer Ingelheim International Gmbh | Inhibitors of human immunodeficiency virus replication |
| CA2705318C (en) | 2007-11-15 | 2013-12-31 | Boehringer Ingelheim International Gmbh | Inhibitors of human immunodeficiency virus replication |
| ES2463720T3 (es) | 2007-11-16 | 2014-05-29 | Gilead Sciences, Inc. | Inhibidores de la replicación del virus de inmunodeficiencia humana |
| EA201200631A1 (ru) | 2007-11-16 | 2012-11-30 | Джилид Сайенсиз, Инк. | Ингибиторы репликации вируса иммунодефицита человека |
| CN101970741B (zh) | 2007-11-23 | 2014-09-03 | 皇家飞利浦电子股份有限公司 | 隔间 |
| TW200942243A (en) * | 2008-03-05 | 2009-10-16 | Biocryst Pharm Inc | Antiviral therapeutic agents |
| US8129398B2 (en) * | 2008-03-19 | 2012-03-06 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| GB0813980D0 (en) | 2008-07-31 | 2008-09-10 | Univ St Andrews | Control of relaxation oscillations in intracavity optical parametric oscillato rs |
| JP5331404B2 (ja) | 2008-08-01 | 2013-10-30 | 国立大学法人 東京医科歯科大学 | 先天性異常症の染色体欠失の検出方法 |
| GB0908394D0 (en) | 2009-05-15 | 2009-06-24 | Univ Leuven Kath | Novel viral replication inhibitors |
| US8338441B2 (en) * | 2009-05-15 | 2012-12-25 | Gilead Sciences, Inc. | Inhibitors of human immunodeficiency virus replication |
| GB0913636D0 (en) | 2009-08-05 | 2009-09-16 | Univ Leuven Kath | Novel viral replication inhibitors |
| WO2011049987A2 (en) * | 2009-10-20 | 2011-04-28 | Eiger Biopharmaceuticals, Inc. | Azaindazoles to treat flaviviridae virus infection |
| US20120316161A1 (en) | 2009-12-23 | 2012-12-13 | Katholieke Universiteit Leuven | Novel antiviral compounds |
| US8716293B2 (en) * | 2010-04-02 | 2014-05-06 | Janssen R&D Ireland | Macrocyclic integrase inhibitors |
| AU2011274322B2 (en) | 2010-07-02 | 2015-08-13 | Gilead Sciences, Inc. | Naphth- 2 -ylacetic acid derivatives to treat AIDS |
| BR112012033689A2 (pt) | 2010-07-02 | 2019-09-24 | Gilead Sciences Inc | derivados de ácido 2-quinolinil-acético como compostos de hiv antivirais |
| US8633200B2 (en) * | 2010-09-08 | 2014-01-21 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| AU2011330850B2 (en) | 2010-11-15 | 2016-01-28 | Viiv Healthcare Uk Limited | Inhibitors of HIV replication |
| NZ610315A (en) * | 2010-11-15 | 2015-08-28 | Univ Leuven Kath | Antiviral condensed heterocyclic compounds |
| US8791108B2 (en) | 2011-08-18 | 2014-07-29 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| US8629276B2 (en) | 2012-02-15 | 2014-01-14 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| US9034882B2 (en) | 2012-03-05 | 2015-05-19 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| US9006235B2 (en) | 2012-03-06 | 2015-04-14 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| US8906929B2 (en) | 2012-08-16 | 2014-12-09 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
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Also Published As
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| MX2015001899A (es) | 2015-05-07 |
| JP6214657B2 (ja) | 2017-10-18 |
| JP2015524841A (ja) | 2015-08-27 |
| SG11201500887QA (en) | 2015-03-30 |
| TW201412750A (zh) | 2014-04-01 |
| BR112015003175A2 (pt) | 2017-08-08 |
| US8906929B2 (en) | 2014-12-09 |
| AU2013302873A1 (en) | 2015-04-02 |
| IL237154A (en) | 2017-03-30 |
| WO2014028384A1 (en) | 2014-02-20 |
| CA2882077A1 (en) | 2014-02-20 |
| KR20150042830A (ko) | 2015-04-21 |
| EP2888266B1 (en) | 2017-01-11 |
| CN104583214A (zh) | 2015-04-29 |
| US20140051692A1 (en) | 2014-02-20 |
| CN104583214B (zh) | 2017-06-09 |
| EP2888266A1 (en) | 2015-07-01 |
| AU2013302873B2 (en) | 2017-02-02 |
| EA201590358A1 (ru) | 2015-05-29 |
| IL237154A0 (en) | 2015-04-30 |
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