ES2623777T3 - 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
- ES2623777T3 ES2623777T3 ES14725559.0T ES14725559T ES2623777T3 ES 2623777 T3 ES2623777 T3 ES 2623777T3 ES 14725559 T ES14725559 T ES 14725559T ES 2623777 T3 ES2623777 T3 ES 2623777T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- equiv
- mmol
- haloalkyl
- methylimidazo
- 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.)
- Active
Links
- 239000003112 inhibitor Substances 0.000 title description 16
- 241000725303 Human immunodeficiency virus Species 0.000 title description 10
- 230000029812 viral genome replication Effects 0.000 title 1
- -1 homopiperidinyl Chemical group 0.000 abstract description 33
- 150000001875 compounds Chemical class 0.000 abstract description 14
- 150000003839 salts Chemical class 0.000 abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 5
- 239000001257 hydrogen Substances 0.000 abstract description 5
- 125000000217 alkyl group Chemical group 0.000 abstract 15
- 125000001188 haloalkyl group Chemical group 0.000 abstract 5
- 125000003342 alkenyl group Chemical group 0.000 abstract 4
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 4
- 125000001475 halogen functional group Chemical group 0.000 abstract 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 4
- 125000001424 substituent group Chemical group 0.000 abstract 4
- 125000003545 alkoxy group Chemical group 0.000 abstract 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 abstract 2
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 2
- 125000004438 haloalkoxy group Chemical group 0.000 abstract 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 2
- 125000003302 alkenyloxy group Chemical group 0.000 abstract 1
- 125000002393 azetidinyl group Chemical group 0.000 abstract 1
- 125000004432 carbon atom Chemical group C* 0.000 abstract 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 abstract 1
- 125000000392 cycloalkenyl group Chemical group 0.000 abstract 1
- 125000002541 furyl group Chemical group 0.000 abstract 1
- 125000002883 imidazolyl group Chemical group 0.000 abstract 1
- 125000001786 isothiazolyl group Chemical group 0.000 abstract 1
- 125000000842 isoxazolyl group Chemical group 0.000 abstract 1
- 125000002757 morpholinyl group Chemical group 0.000 abstract 1
- 125000001715 oxadiazolyl group Chemical group 0.000 abstract 1
- 125000002971 oxazolyl group Chemical group 0.000 abstract 1
- 125000004193 piperazinyl group Chemical group 0.000 abstract 1
- 125000003386 piperidinyl group Chemical group 0.000 abstract 1
- 125000003226 pyrazolyl group Chemical group 0.000 abstract 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 abstract 1
- 125000000168 pyrrolyl group Chemical group 0.000 abstract 1
- 125000001113 thiadiazolyl group Chemical group 0.000 abstract 1
- 125000000335 thiazolyl group Chemical group 0.000 abstract 1
- 125000001544 thienyl group Chemical group 0.000 abstract 1
- 125000001425 triazolyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 29
- 239000000243 solution Substances 0.000 description 24
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 23
- 239000000203 mixture Substances 0.000 description 22
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 239000012043 crude product Substances 0.000 description 16
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
- 239000007832 Na2SO4 Substances 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 125000005336 allyloxy group Chemical group 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- 238000000034 method Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 8
- 239000005695 Ammonium acetate Substances 0.000 description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 229940043376 ammonium acetate Drugs 0.000 description 8
- 235000019257 ammonium acetate Nutrition 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- 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 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 159000000000 sodium salts Chemical class 0.000 description 7
- 208000030507 AIDS Diseases 0.000 description 6
- 208000031886 HIV Infections Diseases 0.000 description 6
- 208000037357 HIV infectious disease Diseases 0.000 description 6
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- ZTMVKMHUHTXAAI-SFHVURJKSA-N 5-(4,4-dimethylpiperidin-1-yl)-6-[(1S)-2-methoxy-1-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-7-methylimidazo[1,2-a]pyridine-2-carboxylic acid Chemical compound COC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(cn2c1N1CCC(C)(C)CC1)C(O)=O ZTMVKMHUHTXAAI-SFHVURJKSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 239000007821 HATU Substances 0.000 description 5
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
- 239000002027 dichloromethane extract Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-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
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 3
- 229940124522 antiretrovirals Drugs 0.000 description 3
- 239000003903 antiretrovirus agent Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000004030 hiv protease inhibitor Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- SWWHMIZLLVXNME-UHFFFAOYSA-N tert-butyl 6-amino-2-chloro-4-methylpyridine-3-carboxylate Chemical compound Cc1cc(N)nc(Cl)c1C(=O)OC(C)(C)C SWWHMIZLLVXNME-UHFFFAOYSA-N 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 3
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- DYAAHGCWBJBFLL-UHFFFAOYSA-N 5-chloro-2-ethoxycarbonyl-7-methylimidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound CCOC(=O)c1cn2c(Cl)c(C(O)=O)c(C)cc2n1 DYAAHGCWBJBFLL-UHFFFAOYSA-N 0.000 description 2
- 229940122440 HIV protease inhibitor Drugs 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 238000011225 antiretroviral therapy Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine Chemical group 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 2
- SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 2
- VICYTAYPKBLQFB-UHFFFAOYSA-N ethyl 3-bromo-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CBr VICYTAYPKBLQFB-UHFFFAOYSA-N 0.000 description 2
- DJQPQGOIQVKXER-UHFFFAOYSA-N ethyl 5-chloro-6-(2-methoxy-2-oxoacetyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylate Chemical compound CCOC(=O)c1cn2c(Cl)c(C(=O)C(=O)OC)c(C)cc2n1 DJQPQGOIQVKXER-UHFFFAOYSA-N 0.000 description 2
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000002835 hiv fusion inhibitor Substances 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 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 2
- XTYSXGHMTNTKFH-BDEHJDMKSA-N (2s)-1-[(2s,4r)-4-benzyl-2-hydroxy-5-[[(1s,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]amino]-5-oxopentyl]-n-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide;hydrate Chemical compound O.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 XTYSXGHMTNTKFH-BDEHJDMKSA-N 0.000 description 1
- PQXWYQZQCWWMDQ-UHFFFAOYSA-N (4-fluoro-3-methylphenyl)methanamine Chemical compound CC1=CC(CN)=CC=C1F PQXWYQZQCWWMDQ-UHFFFAOYSA-N 0.000 description 1
- ASSJTMUEFHUKMJ-UHFFFAOYSA-N 1-acetyl-n-[3-[4-[(4-carbamoylphenyl)methyl]piperidin-1-yl]propyl]-n-(3-chloro-4-methylphenyl)piperidine-4-carboxamide Chemical compound C1CN(C(=O)C)CCC1C(=O)N(C=1C=C(Cl)C(C)=CC=1)CCCN1CCC(CC=2C=CC(=CC=2)C(N)=O)CC1 ASSJTMUEFHUKMJ-UHFFFAOYSA-N 0.000 description 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- BAPQGVJWZUSJIR-UHFFFAOYSA-N 2-(1-bromothiolan-1-yl)acetonitrile Chemical class C(#N)CS1(CCCC1)Br BAPQGVJWZUSJIR-UHFFFAOYSA-N 0.000 description 1
- MBIJHJYDUDWVFT-UHFFFAOYSA-N 2-amino-3-(4-fluorophenyl)propanenitrile Chemical compound N#CC(N)CC1=CC=C(F)C=C1 MBIJHJYDUDWVFT-UHFFFAOYSA-N 0.000 description 1
- FPTCVTJCJMVIDV-UHFFFAOYSA-N 2-phenylacetohydrazide Chemical compound NNC(=O)CC1=CC=CC=C1 FPTCVTJCJMVIDV-UHFFFAOYSA-N 0.000 description 1
- ZNGINKJHQQQORD-UHFFFAOYSA-N 2-trimethylsilylethanol Chemical compound C[Si](C)(C)CCO ZNGINKJHQQQORD-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- KGPOBTYJFRWXRP-UHFFFAOYSA-N 5-(4,4-dimethylpiperidin-1-yl)-2-ethoxycarbonyl-7-methylimidazo[1,2-a]pyridine-6-carboxylic acid Chemical compound CCOC(=O)c1cn2c(N3CCC(C)(C)CC3)c(C(O)=O)c(C)cc2n1 KGPOBTYJFRWXRP-UHFFFAOYSA-N 0.000 description 1
- KWFATEIGYFTXOW-UHFFFAOYSA-N 6-O-tert-butyl 2-O-ethyl 5-(4,4-dimethylpiperidin-1-yl)-7-methylimidazo[1,2-a]pyridine-2,6-dicarboxylate Chemical compound CCOC(=O)c1cn2c(N3CCC(C)(C)CC3)c(C(=O)OC(C)(C)C)c(C)cc2n1 KWFATEIGYFTXOW-UHFFFAOYSA-N 0.000 description 1
- XRLDNPQNIAUDBH-UHFFFAOYSA-N 6-O-tert-butyl 2-O-ethyl 5-chloro-7-methylimidazo[1,2-a]pyridine-2,6-dicarboxylate Chemical compound CCOC(=O)c1cn2c(Cl)c(C(=O)OC(C)(C)C)c(C)cc2n1 XRLDNPQNIAUDBH-UHFFFAOYSA-N 0.000 description 1
- XHKBXJGZGBAZFG-FQEVSTJZSA-N 6-[(1S)-2-methoxy-1-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-7-methyl-5-(4-methyl-4-prop-2-enoxypiperidin-1-yl)imidazo[1,2-a]pyridine-2-carboxylic acid Chemical compound COC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(cn2c1N1CCC(C)(CC1)OCC=C)C(O)=O XHKBXJGZGBAZFG-FQEVSTJZSA-N 0.000 description 1
- PJKZYCGHBWHEQU-UHFFFAOYSA-N 6-[(2-methylpropan-2-yl)oxycarbonyl]pyridine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)C1=CC=CC(C(O)=O)=N1 PJKZYCGHBWHEQU-UHFFFAOYSA-N 0.000 description 1
- AXRYRYVKAWYZBR-UHFFFAOYSA-N Atazanavir Natural products C=1C=C(C=2N=CC=CC=2)C=CC=1CN(NC(=O)C(NC(=O)OC)C(C)(C)C)CC(O)C(NC(=O)C(NC(=O)OC)C(C)(C)C)CC1=CC=CC=C1 AXRYRYVKAWYZBR-UHFFFAOYSA-N 0.000 description 1
- 108010019625 Atazanavir Sulfate Proteins 0.000 description 1
- 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 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 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 1
- 108010032976 Enfuvirtide Proteins 0.000 description 1
- 108010002459 HIV Integrase Proteins 0.000 description 1
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 description 1
- 229940099797 HIV integrase inhibitor Drugs 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229960001830 amprenavir Drugs 0.000 description 1
- YMARZQAQMVYCKC-OEMFJLHTSA-N amprenavir Chemical group C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 YMARZQAQMVYCKC-OEMFJLHTSA-N 0.000 description 1
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 229940124411 anti-hiv antiviral agent Drugs 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229960003277 atazanavir Drugs 0.000 description 1
- AXRYRYVKAWYZBR-GASGPIRDSA-N atazanavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)[C@@H](O)CN(CC=1C=CC(=CC=1)C=1N=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C1=CC=CC=C1 AXRYRYVKAWYZBR-GASGPIRDSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 150000003842 bromide salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000034303 cell budding Effects 0.000 description 1
- 238000001023 centrifugal evaporation Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229960005319 delavirdine Drugs 0.000 description 1
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229960003804 efavirenz Drugs 0.000 description 1
- 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 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- PEASPLKKXBYDKL-FXEVSJAOSA-N enfuvirtide Chemical group 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
- 239000012259 ether extract Substances 0.000 description 1
- GRUZZCZNSSJZFB-UHFFFAOYSA-N ethyl 6-(2-methoxy-2-oxoacetyl)-7-methyl-5-(4-methyl-4-prop-2-enoxypiperidin-1-yl)imidazo[1,2-a]pyridine-2-carboxylate Chemical compound CCOC(=O)c1cn2c(N3CCC(C)(CC3)OCC=C)c(C(=O)C(=O)OC)c(C)cc2n1 GRUZZCZNSSJZFB-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- FQYYIPZPELSLDK-UHFFFAOYSA-N ethyl pyridine-2-carboxylate Chemical compound CCOC(=O)C1=CC=CC=N1 FQYYIPZPELSLDK-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229960003142 fosamprenavir Drugs 0.000 description 1
- MLBVMOWEQCZNCC-OEMFJLHTSA-N fosamprenavir Chemical compound C([C@@H]([C@H](OP(O)(O)=O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 MLBVMOWEQCZNCC-OEMFJLHTSA-N 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 239000003084 hiv integrase inhibitor Substances 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 210000003692 ilium Anatomy 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 229960001936 indinavir Drugs 0.000 description 1
- 229940121292 leronlimab Drugs 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229960004525 lopinavir Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 229960001238 methylnicotinate Drugs 0.000 description 1
- FVYBAJYRRIYNBN-UHFFFAOYSA-N n'-hydroxy-2-phenylethanimidamide Chemical compound ON=C(N)CC1=CC=CC=C1 FVYBAJYRRIYNBN-UHFFFAOYSA-N 0.000 description 1
- 229960000884 nelfinavir Drugs 0.000 description 1
- 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 1
- 229960000689 nevirapine Drugs 0.000 description 1
- 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- PUPAWTXNPAJCHR-UHFFFAOYSA-N oxazaborole Chemical compound O1C=CB=N1 PUPAWTXNPAJCHR-UHFFFAOYSA-N 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
- YIQPUIGJQJDJOS-UHFFFAOYSA-N plerixafor Chemical group C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 YIQPUIGJQJDJOS-UHFFFAOYSA-N 0.000 description 1
- 229960002169 plerixafor Drugs 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000005070 ripening Effects 0.000 description 1
- 229960000311 ritonavir Drugs 0.000 description 1
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
- 229960001852 saquinavir Drugs 0.000 description 1
- 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 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- STKQJGNQQYWQEE-UHFFFAOYSA-N tert-butyl 2,6-dichloro-4-methylpyridine-3-carboxylate Chemical compound Cc1cc(Cl)nc(Cl)c1C(=O)OC(C)(C)C STKQJGNQQYWQEE-UHFFFAOYSA-N 0.000 description 1
- MDDXDIWSPBEWEB-UHFFFAOYSA-N tert-butyl 6-amino-2-(4,4-dimethylpiperidin-1-yl)-4-methylpyridine-3-carboxylate Chemical compound Cc1cc(N)nc(N2CCC(C)(C)CC2)c1C(=O)OC(C)(C)C MDDXDIWSPBEWEB-UHFFFAOYSA-N 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-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
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000003643 water by type Substances 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
- A61K31/435—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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- 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
- C07D471/02—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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- AIDS & HIV (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361780179P | 2013-03-13 | 2013-03-13 | |
| US201361780179P | 2013-03-13 | ||
| PCT/US2014/022354 WO2014164409A1 (en) | 2013-03-13 | 2014-03-10 | Inhibitors of human immunodeficiency virus replication |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2623777T3 true ES2623777T3 (es) | 2017-07-12 |
Family
ID=50771321
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14725559.0T Active ES2623777T3 (es) | 2013-03-13 | 2014-03-10 | Inhibidores de la replicación del virus de la inmunodeficiencia humana |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US9655889B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2970273B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2016512507A (cg-RX-API-DMAC7.html) |
| CN (1) | CN105008358B (cg-RX-API-DMAC7.html) |
| ES (1) | ES2623777T3 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2014164409A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9409922B2 (en) | 2014-02-18 | 2016-08-09 | Bristol-Myers Squibb Company | Imidazopyridine macrocycles as inhibitors of human immunodeficiency virus replication |
| WO2015126765A1 (en) | 2014-02-19 | 2015-08-27 | Bristol-Myers Squibb Company | 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 |
| BR112017003663A2 (pt) | 2014-08-27 | 2017-11-28 | Viiv Healthcare Uk No 5 Ltd | composto, composição, e, método para tratamento de infecção por hiv. |
| HK1247203A1 (zh) * | 2015-01-28 | 2018-09-21 | 上海复旦张江生物医药股份有限公司 | 取代的咪唑并[1，2-α]吡啶-2-基胺化合物及其药物组合物和使用方法 |
| 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 |
| WO2017006261A1 (en) * | 2015-07-06 | 2017-01-12 | VIIV Healthcare UK (No.5) Limited | Pyridin-3-yl acetic acid derivatives as inhibitors of human immunodeficiency virus replication |
| KR20180025926A (ko) * | 2015-07-08 | 2018-03-09 | 비브 헬스케어 유케이 (넘버5) 리미티드 | 인간 면역결핍 바이러스 복제의 억제제로서의 피리딘-3-일 아세트산 유도체 |
| JP2018522924A (ja) | 2015-08-10 | 2018-08-16 | ヴィーブ ヘルスケア ユーケー（ナンバー５）リミテッド | ヒト免疫不全ウイルス複製の阻害剤としてのイミダゾピリジン大環状化合物 |
| JP2023536893A (ja) * | 2020-08-14 | 2023-08-30 | シャンハイ フダン－チャンジャン バイオ－ファーマシューティカル カンパニー リミテッド | Ｊａｋ阻害剤の塩形、結晶及びその製造方法と使用 |
| CN113698342B (zh) * | 2021-10-29 | 2021-12-31 | 南京恒远科技开发有限公司 | 一种奥布替尼关键中间体杂环类化合物2,6-二氯烟酸的制备方法 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR910011852A (ko) * | 1989-12-04 | 1991-08-07 | 폴 디. 매튜카이티스 | 신경독 장해 치료용 이미다조[1,2-a]피리디닐알킬 화합물 |
| MXPA04002136A (es) | 2001-09-26 | 2005-03-07 | Bayer Pharmaceuticals Corp | Derivados de 1,6-naftiridina y su uso para el tratamiento de la diabetes y trastornos relacionados. |
| US20080234318A1 (en) * | 2005-08-31 | 2008-09-25 | Kristjan Gudmundsson | Chemical Compounds |
| US7939545B2 (en) | 2006-05-16 | 2011-05-10 | Boehringer Ingelheim International Gmbh | Inhibitors of human immunodeficiency virus replication |
| EP2574610A1 (en) | 2007-11-15 | 2013-04-03 | Gilead Sciences, Inc. | Inhibitors of human immonodeficiency virus replication |
| HRP20120328T2 (hr) | 2007-11-15 | 2012-09-30 | Gilead Sciences | Inhibitori replikacije virusa humane imunodeficijencije |
| CA2705338A1 (en) * | 2007-11-16 | 2009-05-22 | Boehringer Ingelheim International Gmbh | Inhibitors of human immunodeficiency virus replication |
| KR20100097156A (ko) | 2007-11-16 | 2010-09-02 | 베링거 인겔하임 인터내셔날 게엠베하 | 사람 면역결핍 바이러스 복제의 억제제 |
| WO2010032195A1 (en) * | 2008-09-16 | 2010-03-25 | Csir | Imidazopyridines and imidazopyrimidines as hiv-i reverse transcriptase inhibitors |
| 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 |
| CA2781780C (en) | 2009-12-23 | 2015-02-17 | Katholieke Universiteit Leuven | Novel antiviral compounds |
| NZ604716A (en) | 2010-07-02 | 2014-12-24 | Gilead Sciences Inc | 2-quinolinyl-acetic acid derivatives as hiv antiviral compounds |
| MA34397B1 (fr) | 2010-07-02 | 2013-07-03 | Gilead Sciences Inc | Dérivés d'acide napht-2-ylacétique dans le traitement du sida |
| 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 |
| MX2013005478A (es) | 2010-11-15 | 2013-08-29 | Univ Leuven Kath | Compuestos heterociclicos condensados antivirales. |
| US8791108B2 (en) * | 2011-08-18 | 2014-07-29 | Bristol-Myers Squibb Company | Inhibitors of human immunodeficiency virus replication |
-
2014
- 2014-03-10 US US14/770,702 patent/US9655889B2/en not_active Expired - Fee Related
- 2014-03-10 EP EP14725559.0A patent/EP2970273B1/en not_active Not-in-force
- 2014-03-10 WO PCT/US2014/022354 patent/WO2014164409A1/en not_active Ceased
- 2014-03-10 CN CN201480013594.8A patent/CN105008358B/zh not_active Expired - Fee Related
- 2014-03-10 ES ES14725559.0T patent/ES2623777T3/es active Active
- 2014-03-10 JP JP2016500947A patent/JP2016512507A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN105008358B (zh) | 2017-12-29 |
| EP2970273B1 (en) | 2017-03-01 |
| WO2014164409A1 (en) | 2014-10-09 |
| JP2016512507A (ja) | 2016-04-28 |
| US9655889B2 (en) | 2017-05-23 |
| EP2970273A1 (en) | 2016-01-20 |
| US20160000771A1 (en) | 2016-01-07 |
| CN105008358A (zh) | 2015-10-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2623777T3 (es) | Inhibidores de la replicación del virus de la inmunodeficiencia humana | |
| AU2020343671B2 (en) | RIP1 inhibitory compounds and methods for making and using the same | |
| ES2972512T3 (es) | Compuestos de aminoácido y métodos de uso | |
| ES2877595T3 (es) | Compuestos sustituidos de 8-oxetan-3-il-3,8-diazabiciclo[3.2.1]octan-3-ilo como inhibidores del VIH | |
| ES2606486T3 (es) | Pirimidinas fusionadas como inhibidores de la replicación del virus de inmunodeficiencia | |
| ES2654173T3 (es) | Inhibidores de la replicación del virus de la inmunodeficiencia humana | |
| WO2017133667A1 (en) | Pyrimidine and pyridine derivatives and use in treatment, amelioration or prevention of influenza thereof | |
| ES2710190T3 (es) | Derivados de 4-azaindol | |
| ES2974494T3 (es) | Compuestos tricíclicos fusionados de piridazinona útiles para tratar las infecciones por ortomixovirus | |
| WO2018237370A1 (en) | Heteroaryl compounds as inhibitors of necrosis, composition and method using the same | |
| KR20230027275A (ko) | Hiv 치료용 캡시드 저해제 | |
| ES2957767T3 (es) | Triterpenoides modificados en C-3 y C-17 como inhibidores del VIH-1 | |
| AU2022202886B2 (en) | Quinazoline Compounds, Preparation Method, Use, and Pharmaceutical Composition Thereof | |
| JP2018522909A (ja) | ヒト免疫不全ウイルス複製の阻害剤としての５−（ｎ−縮合三環式アリールテトラヒドロイソキノリン−６−イル）ピリジン−３−イル酢酸誘導体 | |
| US20200016136A1 (en) | Pyridin-3-yl acetic acid derivatives as inhibitors of human immunodeficiency virus replication | |
| ES2761569T3 (es) | Derivados aminopiridínicos como inhibidores de fosfatidilinositol 3-cinasas | |
| JP7646671B2 (ja) | Ｂｔｋ阻害剤 | |
| WO2019149734A1 (en) | Cycloalkyl substituted pyrazolopyrimidines having activity against rsv | |
| CA2963054C (en) | Piperidine substituted tricyclic pyrazolo[1,5-a]pyrimidine derivatives with inhibitory activity on the replication of the respiratory syncytial virus (rsv) | |
| JP2024502163A (ja) | ２－アミノピリミジン系化合物、その医薬組成物、及び使用 | |
| JP2018522913A (ja) | ヒト免疫不全ウイルス複製の阻害剤としての５−（ｎ−［６，５］−縮合二環式アリールテトラヒドロイソキノリン−６−イル）ピリジン−３−イル酢酸誘導体 | |
| ES2916549T3 (es) | Compuestos heteroarilo como inhibidores de necrosis y composición relacionada | |
| WO2015123182A1 (en) | Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication | |
| IL315162A (en) | Polo-like kinase 4 (plk4) inhibitors, pharmaceutical compositions, methods of preparation and uses thereof | |
| JP2019515000A (ja) | ヒト免疫不全ウイルス複製の阻害剤としてのピリジン−３−イル酢酸誘導体 |