AU2005250356C1 - Bicyclic heterocycles as HIV integrase inhibitors - Google Patents
Bicyclic heterocycles as HIV integrase inhibitors Download PDFInfo
- Publication number
- AU2005250356C1 AU2005250356C1 AU2005250356A AU2005250356A AU2005250356C1 AU 2005250356 C1 AU2005250356 C1 AU 2005250356C1 AU 2005250356 A AU2005250356 A AU 2005250356A AU 2005250356 A AU2005250356 A AU 2005250356A AU 2005250356 C1 AU2005250356 C1 AU 2005250356C1
- Authority
- AU
- Australia
- Prior art keywords
- oxo
- methyl
- oxazine
- fluoro
- hydroxy
- 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.)
- Ceased
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- 229940099797 HIV integrase inhibitor Drugs 0.000 title claims description 12
- 239000003084 hiv integrase inhibitor Substances 0.000 title claims description 12
- 125000002618 bicyclic heterocycle group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 367
- -1 cyclic bicyclic pyrimidinone compounds Chemical class 0.000 claims abstract description 147
- 238000000034 method Methods 0.000 claims abstract description 122
- 208000030507 AIDS Diseases 0.000 claims abstract description 90
- 208000031886 HIV Infections Diseases 0.000 claims abstract description 62
- 208000037357 HIV infectious disease Diseases 0.000 claims abstract description 60
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims abstract description 60
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 210
- 239000000203 mixture Substances 0.000 claims description 179
- 229910052739 hydrogen Inorganic materials 0.000 claims description 134
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 103
- JROPBYGZSRBHDV-UHFFFAOYSA-N oxazine-2-carboxamide Chemical compound NC(=O)N1OC=CC=C1 JROPBYGZSRBHDV-UHFFFAOYSA-N 0.000 claims description 60
- 239000003112 inhibitor Substances 0.000 claims description 57
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- 229910052757 nitrogen Inorganic materials 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 41
- 150000003839 salts Chemical class 0.000 claims description 36
- 239000012453 solvate Substances 0.000 claims description 35
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 33
- 239000003795 chemical substances by application Substances 0.000 claims description 32
- 239000002777 nucleoside Substances 0.000 claims description 26
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 24
- 150000002431 hydrogen Chemical class 0.000 claims description 22
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 10
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 10
- 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
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims description 9
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims description 9
- 230000034303 cell budding Effects 0.000 claims description 9
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- 230000035800 maturation Effects 0.000 claims description 9
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- 239000002835 hiv fusion inhibitor Substances 0.000 claims description 8
- 239000004030 hiv protease inhibitor Substances 0.000 claims description 8
- 229910052786 argon Inorganic materials 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000001475 halogen functional group Chemical group 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 125000002393 azetidinyl group Chemical group 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000005059 halophenyl group Chemical group 0.000 claims description 3
- 125000005429 oxyalkyl group Chemical group 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- DWLVWMUCHSLGSU-UHFFFAOYSA-N dimethylcarbamic acid Chemical compound CN(C)C(O)=O DWLVWMUCHSLGSU-UHFFFAOYSA-N 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- LDSKYBVNIGKJHA-UHFFFAOYSA-N 2h-1,4-oxazine-2-carboxamide Chemical compound NC(=O)C1OC=CN=C1 LDSKYBVNIGKJHA-UHFFFAOYSA-N 0.000 claims 10
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- MABWPFNVENFTKF-UHFFFAOYSA-N 1,4-oxazepine-2-carboxamide Chemical compound NC(=O)C1=CN=CC=CO1 MABWPFNVENFTKF-UHFFFAOYSA-N 0.000 claims 2
- AVAIDEMSYWGUAS-UHFFFAOYSA-N 3-hydroxy-9,9-dimethyl-4-oxo-1,2,3,6,7,9a-hexahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound OC1C(NC2C(OCCN2C1=O)(C)C)C(=O)N AVAIDEMSYWGUAS-UHFFFAOYSA-N 0.000 claims 2
- AZOLUMIOWNWBDM-UHFFFAOYSA-N OC1C(=NC2=COC=CN2C1=O)C(=O)N Chemical compound OC1C(=NC2=COC=CN2C1=O)C(=O)N AZOLUMIOWNWBDM-UHFFFAOYSA-N 0.000 claims 2
- CXKIFFLNEGHCNT-UHFFFAOYSA-N 10,10-dimethyl-4-oxo-6H-pyrimido[2,1-c][1,4]oxazepine-2-carboxamide Chemical compound CC1(OC=CCN2C1=NC(=CC2=O)C(=O)N)C CXKIFFLNEGHCNT-UHFFFAOYSA-N 0.000 claims 1
- UCIKZFACVAUECI-UHFFFAOYSA-N 3-hydroxy-4-oxo-2,3,6,7-tetrahydro-1H-pyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound OC1C(NC2=COCCN2C1=O)C(=O)N UCIKZFACVAUECI-UHFFFAOYSA-N 0.000 claims 1
- KATSFXHQLOKKKZ-UHFFFAOYSA-N 3-hydroxy-9,9-dimethyl-n-[(2-methylsulfonylphenyl)methyl]-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=CC=C1S(C)(=O)=O KATSFXHQLOKKKZ-UHFFFAOYSA-N 0.000 claims 1
- OCNAFKXMEPGDIR-UHFFFAOYSA-N 9,9-dimethyl-4-oxopyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OC=CN2C1=NC(C(N)=O)=CC2=O OCNAFKXMEPGDIR-UHFFFAOYSA-N 0.000 claims 1
- HWHVFKMHOIUEDB-UHFFFAOYSA-N CC=1N2C(=COC1)N=C(C(C2=O)C)C(=O)N Chemical compound CC=1N2C(=COC1)N=C(C(C2=O)C)C(=O)N HWHVFKMHOIUEDB-UHFFFAOYSA-N 0.000 claims 1
- PYYHHGCMPCSNFK-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1 PYYHHGCMPCSNFK-UHFFFAOYSA-N 0.000 claims 1
- ZAYNAGILDTUKKA-UHFFFAOYSA-N n-[[4-fluoro-2-(2-oxoazetidin-1-yl)phenyl]methyl]-3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound CC1(C)OCCN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1N1CCC1=O ZAYNAGILDTUKKA-UHFFFAOYSA-N 0.000 claims 1
- 230000003612 virological effect Effects 0.000 abstract description 12
- 108010002459 HIV Integrase Proteins 0.000 abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 5
- 230000010354 integration Effects 0.000 abstract description 4
- 230000009471 action Effects 0.000 abstract description 2
- 239000000543 intermediate Substances 0.000 description 543
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 353
- COEOZBBXBIAOHC-UHFFFAOYSA-N pyrimido[2,1-c][1,4]oxazine-2-carboxamide Chemical compound O1C=CN2C=CC(C(=O)N)=NC2=C1 COEOZBBXBIAOHC-UHFFFAOYSA-N 0.000 description 176
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 173
- 238000005481 NMR spectroscopy Methods 0.000 description 168
- 125000003118 aryl group Chemical group 0.000 description 165
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 141
- 239000007787 solid Substances 0.000 description 141
- 239000000243 solution Substances 0.000 description 139
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 127
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 98
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 96
- 238000005160 1H NMR spectroscopy Methods 0.000 description 81
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 79
- 229910001868 water Inorganic materials 0.000 description 77
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 73
- 239000011541 reaction mixture Substances 0.000 description 67
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 63
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- 235000019441 ethanol Nutrition 0.000 description 54
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- 241000725303 Human immunodeficiency virus Species 0.000 description 48
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 48
- 239000002904 solvent Substances 0.000 description 48
- 239000003921 oil Substances 0.000 description 41
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 40
- 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
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 32
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 31
- 230000000694 effects Effects 0.000 description 31
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 30
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
- 239000011734 sodium Substances 0.000 description 30
- 239000000741 silica gel Substances 0.000 description 29
- 229910002027 silica gel Inorganic materials 0.000 description 29
- 239000000843 powder Substances 0.000 description 28
- 229910004298 SiO 2 Inorganic materials 0.000 description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
- 239000000706 filtrate Substances 0.000 description 25
- WJKJEAGGPROXHV-UHFFFAOYSA-N 9,9-dimethyl-4-oxo-3-phenylmethoxy-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxylic acid Chemical compound CC1(C)OCCN(C2=O)C1=NC(C(O)=O)=C2OCC1=CC=CC=C1 WJKJEAGGPROXHV-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 239000013078 crystal Substances 0.000 description 24
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 23
- 239000000284 extract Substances 0.000 description 23
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 23
- 239000000047 product Substances 0.000 description 23
- 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 22
- 238000004587 chromatography analysis Methods 0.000 description 21
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- 229910000104 sodium hydride Inorganic materials 0.000 description 20
- 229960002555 zidovudine Drugs 0.000 description 20
- 238000004440 column chromatography Methods 0.000 description 19
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
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- 150000001412 amines Chemical class 0.000 description 13
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- PEDCBVRNLWSIIM-UHFFFAOYSA-N ethyl 3-hydroxy-9,9-dimethyl-4-oxo-6,7-dihydropyrimido[2,1-c][1,4]oxazine-2-carboxylate Chemical compound O=C1C(O)=C(C(=O)OCC)N=C2N1CCOC2(C)C PEDCBVRNLWSIIM-UHFFFAOYSA-N 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 13
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- 238000002560 therapeutic procedure Methods 0.000 description 13
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- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 12
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- IIFVWLUQBAIPMJ-UHFFFAOYSA-N (4-fluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1 IIFVWLUQBAIPMJ-UHFFFAOYSA-N 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
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- 229960004748 abacavir Drugs 0.000 description 11
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Classifications
-
- 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
- C07D498/02—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 two hetero rings
- C07D498/04—Ortho-condensed 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
- A61K31/535—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
- A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- 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
- 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
- C07D487/02—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 two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US57551304P | 2004-05-28 | 2004-05-28 | |
| US60/575,513 | 2004-05-28 | ||
| US60337104P | 2004-08-20 | 2004-08-20 | |
| US60/603,371 | 2004-08-20 | ||
| US11/126,891 | 2005-05-11 | ||
| US11/126,891 US7176196B2 (en) | 2004-05-28 | 2005-05-11 | Bicyclic heterocycles as HIV integrase inhibitors |
| PCT/US2005/016473 WO2005118593A1 (en) | 2004-05-28 | 2005-05-12 | Bicyclic heterocycles as hiv integrase inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| AU2005250356A1 AU2005250356A1 (en) | 2005-12-15 |
| AU2005250356B2 AU2005250356B2 (en) | 2011-03-17 |
| AU2005250356C1 true AU2005250356C1 (en) | 2011-10-06 |
Family
ID=35456854
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2005250356A Ceased AU2005250356C1 (en) | 2004-05-28 | 2005-05-12 | Bicyclic heterocycles as HIV integrase inhibitors |
Country Status (26)
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| SI (1) | SI1749011T1 (enExample) |
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| US7115601B2 (en) | 2004-05-18 | 2006-10-03 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| AU2006228278C1 (en) * | 2005-03-31 | 2011-06-23 | Msd Italia S.R.L. | HIV integrase inhibitors |
| US7494984B2 (en) * | 2005-08-31 | 2009-02-24 | Bristol-Myers Squibb Company | Substituted imidazo[1,2-a]pyrimidines as HIV viral DNA integrase inhibitors |
| EP1937678B1 (en) * | 2005-10-04 | 2011-07-27 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Hiv integrase inhibitors |
| US7902182B2 (en) * | 2005-11-16 | 2011-03-08 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| WO2007064316A1 (en) * | 2005-11-30 | 2007-06-07 | Bristol-Myers Squibb Company | Bicyclic heterocycles as hiv integrase inhibitors |
| WO2007064502A1 (en) * | 2005-12-01 | 2007-06-07 | Bristol-Myers Squibb Company | Forms of n-[(4-fluorophenyl)methyl]-4,6,7,9-tetrahydro-3-hydroxy-9,9-dimethyl-4-oxo-pyrimido[2,1-c][1,4]oxazine-2-carboxamide |
| US20070129379A1 (en) * | 2005-12-01 | 2007-06-07 | Bristol-Myers Squibb Company | Hiv integrase inhibitors |
| US7897593B2 (en) * | 2006-05-30 | 2011-03-01 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| US7893055B2 (en) * | 2006-06-28 | 2011-02-22 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| AU2007275805A1 (en) * | 2006-07-19 | 2008-01-24 | University Of Georgia Research Foundation, Inc. | Pyridinone diketo acids: Inhibitors of HIV replication in combination therapy |
| US7763630B2 (en) * | 2007-06-06 | 2010-07-27 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| US8129398B2 (en) * | 2008-03-19 | 2012-03-06 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| AU2009228254A1 (en) * | 2008-03-27 | 2009-10-01 | Bristol-Myers Squibb Company | Crystalline form of N-[[4-fluoro-2- (5-methyl-1H-1,2,4-triazol-1-yl) phenyl]methyl]-4,6,7,9-tetrahydro-3- hydroxy-9,9-dimethyl-4-oxo-pyrimido [2,1-c][1,4]oxazine-2-carboxamide, sodium salt monohydrate |
| EA201170537A1 (ru) * | 2008-10-06 | 2011-12-30 | Мерк Шарп Энд Домэ Корп. | Ингибиторы вич-интегразы |
| US8143244B2 (en) * | 2009-02-26 | 2012-03-27 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
| AU2010305805B2 (en) | 2009-10-13 | 2014-04-03 | Elanco Animal Health Ireland Limited | Macrocyclic integrase inhibitors |
| US8383639B2 (en) | 2009-10-15 | 2013-02-26 | Bristol-Myers Squibb Company | HIV integrase inhibitors |
| EA201270651A1 (ru) | 2009-12-07 | 2013-01-30 | Юниверсити Оф Джорджия Рисерч Фаундейшн, Инк. | Карбоксамиды пиридинон гидроксициклопентила: ингибиторы вич интегразы и области терапевтического применения |
| PT3494972T (pt) | 2010-01-27 | 2024-02-12 | Viiv Healthcare Co | Combinações de dolutegravir e lamivudina para o tratamento de infeção pelo hiv |
| JP5739517B2 (ja) | 2010-04-02 | 2015-06-24 | ヤンセン・アールアンドデイ・アイルランド | 大環状インテグラーゼ阻害剤 |
| WO2012007500A2 (de) | 2010-07-15 | 2012-01-19 | Bayer Cropscience Ag | Neue heterocyclische verbindungen als schädlingsbekämpfungsmittel |
| US8791108B2 (en) | 2011-08-18 | 2014-07-29 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
| CA2856722C (en) | 2011-11-30 | 2022-11-22 | Emory University | Antiviral jak inhibitors useful in treating or preventing retroviral and other viral infections |
| EP2807149A2 (en) * | 2012-01-26 | 2014-12-03 | CRO Consulting Limited | Agents for treating neurodegenerative disorders |
| WO2014099586A1 (en) | 2012-12-17 | 2014-06-26 | Merck Sharp & Dohme Corp. | 4-pyridinonetriazine derivatives as hiv integrase inhibitors |
| WO2014172188A2 (en) | 2013-04-16 | 2014-10-23 | Merck Sharp & Dohme Corp. | 4-pyridone derivative compounds and uses thereof as hiv integrase inhibitors |
| EP3330272B1 (en) | 2013-05-17 | 2021-02-17 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds as hiv integrase inhibitors |
| EP3008044B1 (en) | 2013-06-13 | 2018-11-21 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds as hiv integrase inhibitors |
| UA117499C2 (uk) | 2013-09-27 | 2018-08-10 | Мерк Шарп Енд Доум Корп. | Заміщені похідні хінолізину, які можна використовувати як інгібітори інтегрази віл |
| WO2016187788A1 (en) | 2015-05-25 | 2016-12-01 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds useful for treating hiv infection |
| WO2017087257A1 (en) | 2015-11-17 | 2017-05-26 | Merck Sharp & Dohme Corp. | Amido-substituted pyridotriazine derivatives useful as hiv integrase inhibitors |
| WO2017106071A1 (en) | 2015-12-15 | 2017-06-22 | Merck Sharp & Dohme Corp. | Spirocyclic quinolizine derivatives useful as hiv integrase inhibitors |
| WO2017113288A1 (en) | 2015-12-31 | 2017-07-06 | Merck Sharp & Dohme Corp. | Fused tricyclic heterocyclic compounds as hiv integrase inhibitors |
| JOP20190130A1 (ar) | 2016-12-02 | 2019-06-02 | Merck Sharp & Dohme | مركبات حلقية غير متجانسة رباعية الحلقات مفيدة كمثبطات إنزيم مدمج لفيروس نقص المناعة البشرية (hiv) |
| AU2017367714B2 (en) | 2016-12-02 | 2020-11-12 | Merck Sharp & Dohme Corp. | Tricyclic heterocycle compounds useful as HIV integrase inhibitors |
| WO2018140368A1 (en) | 2017-01-26 | 2018-08-02 | Merck Sharp & Dohme Corp. | Substituted quinolizine derivatives useful as hiv integrase inhibitors |
| WO2021050555A1 (en) * | 2019-09-10 | 2021-03-18 | X-Chem, Inc. | Compositions and uses thereof |
| CN113912622B (zh) * | 2020-07-10 | 2023-12-01 | 上海纽思克生物科技有限公司 | 三环嘧啶酮类化合物、其制备方法、其组合物和用途 |
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| US5693641A (en) * | 1996-08-16 | 1997-12-02 | Berlex Laboratories Inc. | Bicyclic pyrimidine derivatives and their use as anti-coagulants |
| DK1441735T3 (da) | 2001-10-26 | 2006-06-12 | Angeletti P Ist Richerche Bio | N-substituerede hydroxypyrimidinon-carboxamid-inhibitorer af HIV-integrase |
| AU2002334205B2 (en) | 2001-10-26 | 2007-07-05 | Istituto Di Ricerche Di Biologia Molecolara P. Angeletti Spa | Dihydroxypyrimidine carboxamide inhibitors of HIV integrase |
| US7094783B2 (en) | 2002-06-26 | 2006-08-22 | Bristol-Myers Squibb Company | Bicyclic pyrimidinones as coagulation cascade inhibitors |
| KR20050087865A (ko) | 2002-12-27 | 2005-08-31 | 이스티투토 디 리세르쉐 디 비올로지아 몰레콜라레 피. 안젤레티에스.피.에이. | ＨＩＶ 인테그라제 억제제로서 유용한테트라하이드로-4Ｈ-피리도[1,2-ａ]피리미딘 및 관련화합물 |
| AR046938A1 (es) | 2003-12-12 | 2006-01-04 | Merck & Co Inc | Procedimiento para preparar hexahidropirimido[1,2-a]azepin-2-carboxilatos y compuetos similares |
| TW200526635A (en) | 2003-12-22 | 2005-08-16 | Shionogi & Co | Hydroxypyrimidinone derivative having HIV integrase inhibitory activity |
| US20070259894A1 (en) | 2004-12-03 | 2007-11-08 | Kelem Kassahun | Use of Atazanavir for Improving the Pharmacokinetics of Drugs Metabolized by Ugt1a1 |
| AU2006228278C1 (en) | 2005-03-31 | 2011-06-23 | Msd Italia S.R.L. | HIV integrase inhibitors |
-
2005
- 2005-05-11 US US11/126,891 patent/US7176196B2/en not_active Expired - Lifetime
- 2005-05-12 PL PL05750075T patent/PL1749011T3/pl unknown
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- 2005-05-12 MX MXPA06013835A patent/MXPA06013835A/es active IP Right Grant
- 2005-05-12 EP EP05750075A patent/EP1749011B1/en not_active Expired - Lifetime
- 2005-05-12 DK DK05750075T patent/DK1749011T3/da active
- 2005-05-12 HR HR20090005T patent/HRP20090005T3/xx unknown
- 2005-05-12 WO PCT/US2005/016473 patent/WO2005118593A1/en not_active Ceased
- 2005-05-12 DE DE602005010690T patent/DE602005010690D1/de not_active Expired - Lifetime
- 2005-05-12 PT PT05750075T patent/PT1749011E/pt unknown
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- 2005-05-12 RU RU2006146970/04A patent/RU2381228C2/ru not_active IP Right Cessation
- 2005-05-12 AT AT05750075T patent/ATE412656T1/de active
- 2005-05-12 RS RSP-2008/0569A patent/RS50700B/sr unknown
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- 2005-05-12 BR BRPI0511623-6A patent/BRPI0511623A/pt not_active IP Right Cessation
- 2005-05-12 AU AU2005250356A patent/AU2005250356C1/en not_active Ceased
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- 2005-05-25 TW TW094117105A patent/TWI366567B/zh not_active IP Right Cessation
- 2005-05-27 AR ARP050102187A patent/AR049124A1/es not_active Application Discontinuation
- 2005-05-30 PE PE2005000602A patent/PE20060242A1/es not_active Application Discontinuation
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- 2006-08-16 US US11/505,149 patent/US7511037B2/en not_active Expired - Lifetime
- 2006-11-21 IL IL179455A patent/IL179455A/en not_active IP Right Cessation
- 2006-12-19 NO NO20065879A patent/NO20065879L/no not_active Application Discontinuation
- 2006-12-27 KR KR1020067027455A patent/KR101097623B1/ko not_active Expired - Fee Related
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