AU2007336703B9 - Bicyclic pyrimidinones and uses thereof - Google Patents
Bicyclic pyrimidinones and uses thereof Download PDFInfo
- Publication number
- AU2007336703B9 AU2007336703B9 AU2007336703A AU2007336703A AU2007336703B9 AU 2007336703 B9 AU2007336703 B9 AU 2007336703B9 AU 2007336703 A AU2007336703 A AU 2007336703A AU 2007336703 A AU2007336703 A AU 2007336703A AU 2007336703 B9 AU2007336703 B9 AU 2007336703B9
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- Prior art keywords
- hydroxy
- oxo
- carboxylic acid
- preparation
- nmr
- 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.)
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- -1 Bicyclic pyrimidinones Chemical class 0.000 title claims description 28
- 150000001875 compounds Chemical class 0.000 claims abstract description 179
- 238000000034 method Methods 0.000 claims abstract description 172
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 239000000651 prodrug Substances 0.000 claims abstract description 20
- 229940002612 prodrug Drugs 0.000 claims abstract description 20
- 238000011282 treatment Methods 0.000 claims abstract description 17
- 208000036142 Viral infection Diseases 0.000 claims abstract description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 230000009385 viral infection Effects 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 10
- 238000011321 prophylaxis Methods 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims description 232
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 48
- 229910052799 carbon Inorganic materials 0.000 claims description 39
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 13
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 230000003647 oxidation Effects 0.000 claims description 8
- 238000007254 oxidation reaction Methods 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 5
- 208000015181 infectious disease Diseases 0.000 claims description 5
- 125000002950 monocyclic group Chemical group 0.000 claims description 5
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
- 150000003536 tetrazoles Chemical class 0.000 claims description 2
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 2
- 150000003852 triazoles Chemical class 0.000 claims description 2
- 125000006287 difluorobenzyl group Chemical group 0.000 claims 1
- 238000005481 NMR spectroscopy Methods 0.000 description 207
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 195
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 151
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 138
- 239000000047 product Substances 0.000 description 131
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
- 239000000203 mixture Substances 0.000 description 73
- 239000000243 solution Substances 0.000 description 62
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
- IIFVWLUQBAIPMJ-UHFFFAOYSA-N (4-fluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1 IIFVWLUQBAIPMJ-UHFFFAOYSA-N 0.000 description 42
- IXHNFOOSLAWRBQ-UHFFFAOYSA-N (3,4-dichlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C(Cl)=C1 IXHNFOOSLAWRBQ-UHFFFAOYSA-N 0.000 description 40
- 238000006243 chemical reaction Methods 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- 239000007787 solid Substances 0.000 description 36
- 239000000460 chlorine Substances 0.000 description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 239000011734 sodium Substances 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 238000001914 filtration Methods 0.000 description 21
- 229910052757 nitrogen Inorganic materials 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000004440 column chromatography Methods 0.000 description 18
- 238000010992 reflux Methods 0.000 description 18
- 239000012267 brine Substances 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- 239000002904 solvent Substances 0.000 description 16
- 239000000872 buffer Substances 0.000 description 15
- 150000002148 esters Chemical class 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 14
- 102100034343 Integrase Human genes 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 230000035892 strand transfer Effects 0.000 description 13
- 241000725303 Human immunodeficiency virus Species 0.000 description 12
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- 210000004027 cell Anatomy 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 108010061833 Integrases Proteins 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 10
- 239000000758 substrate Substances 0.000 description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 238000003818 flash chromatography Methods 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 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 8
- 230000003612 virological effect Effects 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 238000001228 spectrum Methods 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 108010002459 HIV Integrase Proteins 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 239000012046 mixed solvent Substances 0.000 description 6
- 235000011181 potassium carbonates Nutrition 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
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- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
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- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- NKGXGEHGPYWBDK-BQYQJAHWSA-N dimethyl (e)-2,3-diacetyloxybut-2-enedioate Chemical compound COC(=O)C(\OC(C)=O)=C(/OC(C)=O)C(=O)OC NKGXGEHGPYWBDK-BQYQJAHWSA-N 0.000 description 5
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
- DEPDDPLQZYCHOH-UHFFFAOYSA-N 1h-imidazol-2-amine Chemical compound NC1=NC=CN1 DEPDDPLQZYCHOH-UHFFFAOYSA-N 0.000 description 4
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- FXPAATUDJDSKSM-UHFFFAOYSA-N methyl imidazo[1,2-a]pyrimidine-2-carboxylate Chemical compound C1=CC=NC2=NC(C(=O)OC)=CN21 FXPAATUDJDSKSM-UHFFFAOYSA-N 0.000 description 4
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- PWLVUDBJYDFOJT-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-3-hydroxy-4-oxo-10h-pyrimido[1,2-a]benzimidazole-2-carboxamide Chemical compound N1=C2NC3=CC=CC=C3N2C(=O)C(O)=C1C(=O)NCC1=CC=C(F)C=C1 PWLVUDBJYDFOJT-UHFFFAOYSA-N 0.000 description 1
- JZOQMNPLWWKQKM-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-3-hydroxy-4-oxo-7-(2-pyrrolidin-1-ylethylamino)pyrido[1,2-a]pyrimidine-2-carboxamide Chemical compound C=1N2C(=O)C(O)=C(C(=O)NCC=3C=CC(F)=CC=3)N=C2C=CC=1NCCN1CCCC1 JZOQMNPLWWKQKM-UHFFFAOYSA-N 0.000 description 1
- DGFAKTPESJJDLN-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-3-hydroxy-6-methyl-10-morpholin-4-yl-4-oxopyrimido[1,2-b]indazole-2-carboxamide Chemical compound C=12C3=NC(C(=O)NCC=4C=CC(F)=CC=4)=C(O)C(=O)N3N(C)C2=CC=CC=1N1CCOCC1 DGFAKTPESJJDLN-UHFFFAOYSA-N 0.000 description 1
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- UDYIAZORXJZVIL-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-6-hydroxy-1-methyl-5-oxoimidazo[1,2-a]pyrimidine-7-carboxamide Chemical compound CN1C=CN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1 UDYIAZORXJZVIL-UHFFFAOYSA-N 0.000 description 1
- GORHTMQNKGBUCM-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-6-hydroxy-2-methyl-5-oxo-[1,3]thiazolo[3,2-a]pyrimidine-7-carboxamide Chemical compound S1C(C)=CN(C(C=2O)=O)C1=NC=2C(=O)NCC1=CC=C(F)C=C1 GORHTMQNKGBUCM-UHFFFAOYSA-N 0.000 description 1
- NPUMAGFMQVVVNE-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-6-hydroxy-7-oxo-2-phenyl-1h-pyrazolo[1,5-a]pyrimidine-5-carboxamide Chemical compound N1N2C(=O)C(O)=C(C(=O)NCC=3C=CC(F)=CC=3)N=C2C=C1C1=CC=CC=C1 NPUMAGFMQVVVNE-UHFFFAOYSA-N 0.000 description 1
- JJPLXYCKLJSZBO-UHFFFAOYSA-N n-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-3-hydroxy-10-(2-morpholin-4-ylethyl)-4-oxopyrimido[1,2-a]benzimidazole-2-carboxamide Chemical compound C12=CC=CC=C2N2C(=O)C(O)=C(C(=O)NCC=3C=C(C(Cl)=CC=3)C(F)(F)F)N=C2N1CCN1CCOCC1 JJPLXYCKLJSZBO-UHFFFAOYSA-N 0.000 description 1
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- NQPDZGIKBAWPEJ-UHFFFAOYSA-N pentanoic acid group Chemical class C(CCCC)(=O)O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920001184 polypeptide Chemical group 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
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- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
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- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
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- 125000003226 pyrazolyl group Chemical group 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
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- 125000000547 substituted alkyl group Chemical group 0.000 description 1
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- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- NVOKSDWODAYUNM-UHFFFAOYSA-N tert-butyl 4-[2-[2-[(3,4-dichlorophenyl)methylcarbamoyl]-3-hydroxy-4-oxopyrimido[1,2-a]benzimidazol-10-yl]ethyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CCN1C2=NC(C(=O)NCC=3C=C(Cl)C(Cl)=CC=3)=C(O)C(=O)N2C2=CC=CC=C21 NVOKSDWODAYUNM-UHFFFAOYSA-N 0.000 description 1
- FKBBMUYDNIDGHY-UHFFFAOYSA-N tert-butyl 4-[[7-[(3,4-dichlorophenyl)methylcarbamoyl]-6-hydroxy-5-oxo-[1,3]thiazolo[3,2-a]pyrimidin-2-yl]methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC1=CN2C(=O)C(O)=C(C(=O)NCC=3C=C(Cl)C(Cl)=CC=3)N=C2S1 FKBBMUYDNIDGHY-UHFFFAOYSA-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
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003554 tetrahydropyrrolyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000000034 thioazolyl group Chemical group 0.000 description 1
- 125000005505 thiomorpholino group Chemical group 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
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- 238000012546 transfer Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
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- 229910052725 zinc Inorganic materials 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
-
- 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
- C07D471/02—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 system contains two hetero rings
- C07D471/04—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
- A61K31/495—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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- 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
-
- 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
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
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- 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
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2007336703A AU2007336703B9 (en) | 2006-12-22 | 2007-12-21 | Bicyclic pyrimidinones and uses thereof |
| AU2010201160A AU2010201160A1 (en) | 2006-12-22 | 2010-03-24 | Bicyclic pyrimidinones and uses thereof |
Applications Claiming Priority (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2006907283 | 2006-12-22 | ||
| AU2006907283A AU2006907283A0 (en) | 2006-12-22 | Bicyclic pyrimidinones and uses thereof | |
| AU2007902479 | 2007-05-09 | ||
| AU2007902479A AU2007902479A0 (en) | 2007-05-09 | Bicyclic pyrimidinones and uses thereof (2) | |
| AU2007903401 | 2007-06-25 | ||
| AU2007903401A AU2007903401A0 (en) | 2007-06-25 | Bicyclic pyrimidinodes and uses thereof (3) | |
| AU2007904114 | 2007-07-31 | ||
| AU2007904114A AU2007904114A0 (en) | 2007-07-31 | Bicyclic pyrimidinones and uses thereof (4) | |
| PCT/AU2007/001980 WO2008077188A1 (en) | 2006-12-22 | 2007-12-21 | Bicyclic pyrimidinones and uses thereof |
| AU2007336703A AU2007336703B9 (en) | 2006-12-22 | 2007-12-21 | Bicyclic pyrimidinones and uses thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2010201160A Division AU2010201160A1 (en) | 2006-12-22 | 2010-03-24 | Bicyclic pyrimidinones and uses thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| AU2007336703A1 AU2007336703A1 (en) | 2008-07-03 |
| AU2007336703B2 AU2007336703B2 (en) | 2012-04-12 |
| AU2007336703B9 true AU2007336703B9 (en) | 2014-03-27 |
Family
ID=39562030
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2007336703A Ceased AU2007336703B9 (en) | 2006-12-22 | 2007-12-21 | Bicyclic pyrimidinones and uses thereof |
| AU2010201160A Abandoned AU2010201160A1 (en) | 2006-12-22 | 2010-03-24 | Bicyclic pyrimidinones and uses thereof |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2010201160A Abandoned AU2010201160A1 (en) | 2006-12-22 | 2010-03-24 | Bicyclic pyrimidinones and uses thereof |
Country Status (15)
| Country | Link |
|---|---|
| US (3) | US8143268B2 (enExample) |
| EP (2) | EP2114903B1 (enExample) |
| JP (2) | JP5208962B2 (enExample) |
| KR (2) | KR20090097194A (enExample) |
| CN (1) | CN101880280B (enExample) |
| AR (2) | AR064517A1 (enExample) |
| AT (1) | ATE496898T1 (enExample) |
| AU (2) | AU2007336703B9 (enExample) |
| BR (2) | BRPI0720564A2 (enExample) |
| CA (1) | CA2673183C (enExample) |
| DE (1) | DE602007012308D1 (enExample) |
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Families Citing this family (20)
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| PL2247601T3 (pl) * | 2008-07-02 | 2013-09-30 | Avexa Ltd | Tiazopirymidynony i ich zastosowanie |
| JP5592360B2 (ja) * | 2008-07-02 | 2014-09-17 | アベキサ・リミテッド | イミダゾピリミジノンおよびその使用 |
| BRPI0913934A2 (pt) * | 2008-07-02 | 2015-10-20 | Avexa Ltd | compostos tendo propriedades antivirais |
| CN102336751A (zh) * | 2010-07-16 | 2012-02-01 | 爱维艾珂瑟有限公司 | 新型抗病毒剂 |
| JP6448647B2 (ja) | 2013-09-12 | 2019-01-09 | アリオス バイオファーマ インク． | アザ−ピリドン化合物およびその用途 |
| US10195202B2 (en) | 2013-12-19 | 2019-02-05 | Ptc Therapeutics, Inc. | Methods for modulating the amount of RNA transcripts |
| MX383931B (es) | 2015-03-11 | 2025-03-14 | Janssen Biopharma Inc | Compuestos de aza-piridona y usos de estos. |
| EP3310169B1 (en) | 2015-05-30 | 2023-05-17 | PTC Therapeutics, Inc. | Methods for modulating rna splicing |
| CN108697709A (zh) | 2015-12-10 | 2018-10-23 | Ptc医疗公司 | 用于治疗亨廷顿病的方法 |
| AU2017363369A1 (en) | 2016-11-28 | 2019-05-30 | Ptc Therapeutics, Inc | Methods for modulating RNA splicing |
| AU2018282154B2 (en) | 2017-06-05 | 2022-04-07 | Ptc Therapeutics, Inc. | Compounds for treating huntington's disease |
| US11608501B2 (en) | 2017-06-14 | 2023-03-21 | Ptc Therapeutics, Inc. | Methods for modifying RNA splicing |
| CN111182898B (zh) | 2017-06-28 | 2024-04-16 | Ptc医疗公司 | 用于治疗亨廷顿氏病的方法 |
| WO2019005993A1 (en) | 2017-06-28 | 2019-01-03 | Ptc Therapeutics, Inc. | METHODS OF TREATING HUNTINGTON'S DISEASE |
| BR112020019373A2 (pt) | 2018-03-27 | 2020-12-29 | Ptc Therapeutics, Inc. | Compostos para o tratamento da doença de hutington |
| IL279688B2 (en) | 2018-06-27 | 2025-01-01 | Ptc Therapeutics Inc | Heterocyclic and heteroaryl compounds for the treatment of Huntington's disease |
| EP3814360B8 (en) | 2018-06-27 | 2024-11-06 | PTC Therapeutics, Inc. | Heteroaryl compounds for treating huntington's disease |
| WO2020005877A1 (en) | 2018-06-27 | 2020-01-02 | Ptc Therapeutics, Inc. | Heteroaryl compounds for treating huntington's disease |
| AU2020394867A1 (en) | 2019-12-02 | 2022-05-26 | Storm Therapeutics Limited | Polyheterocyclic compounds as METTL3 inhibitors |
| US12070445B2 (en) * | 2021-08-27 | 2024-08-27 | Wisconsin Alumni Research Foundation | System and assay for monitoring production/release of membrane-lytic toxins in bacteria and compounds for modulating same |
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| WO2007039218A1 (en) * | 2005-10-04 | 2007-04-12 | Istituto Di Ricerche Di Biologia Molecolare P Angeletti Spa | Hiv integrase inhibitors |
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| AU2002241459A1 (en) | 2000-09-20 | 2002-06-11 | Schering Corporation | Substituted imidazoles as dual histamine h1 and h3 agonists or antagonists |
| AR042095A1 (es) | 2002-11-20 | 2005-06-08 | Japan Tobacco Inc | Compuesto 4-oxoquinolina y aplicacion del mismo como inhibidor de integrasa de vih |
| DK1697343T3 (da) | 2003-12-18 | 2009-10-05 | Tibotec Pharm Ltd | Aminobenzimidazoler og benzimidazoler som inhibitorer af replikation af respiratorisk syncytialvirus |
| TW200526635A (en) * | 2003-12-22 | 2005-08-16 | Shionogi & Co | Hydroxypyrimidinone derivative having HIV integrase inhibitory activity |
| AU2005293336B2 (en) | 2004-10-12 | 2009-05-28 | Astrazeneca Ab | Quinazoline derivatives |
| CN101146811B (zh) * | 2005-03-31 | 2012-01-11 | P.安杰莱蒂分子生物学研究所 | Hiv整合酶抑制剂 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007039218A1 (en) * | 2005-10-04 | 2007-04-12 | Istituto Di Ricerche Di Biologia Molecolare P Angeletti Spa | Hiv integrase inhibitors |
Non-Patent Citations (1)
| Title |
|---|
| TISLER, M. et al. Org. Prep. & Proc. Intl. (1990), Vol. 22, No. 4, pages 532-534 * |
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