CA2560071C - Lysine based compounds - Google Patents
Lysine based compounds Download PDFInfo
- Publication number
- CA2560071C CA2560071C CA2560071A CA2560071A CA2560071C CA 2560071 C CA2560071 C CA 2560071C CA 2560071 A CA2560071 A CA 2560071A CA 2560071 A CA2560071 A CA 2560071A CA 2560071 C CA2560071 C CA 2560071C
- Authority
- CA
- Canada
- Prior art keywords
- group
- compound
- carbon atoms
- formula
- pyridyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 261
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 title abstract description 13
- 239000004472 Lysine Substances 0.000 title abstract description 13
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 27
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 17
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 136
- -1 methylenedioxy group Chemical group 0.000 claims description 122
- 125000000217 alkyl group Chemical group 0.000 claims description 79
- 229910052739 hydrogen Inorganic materials 0.000 claims description 67
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 45
- 229910052727 yttrium Inorganic materials 0.000 claims description 34
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 32
- 238000011282 treatment Methods 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 24
- 208000031886 HIV Infections Diseases 0.000 claims description 20
- 229910052740 iodine Inorganic materials 0.000 claims description 18
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 18
- 208000037357 HIV infectious disease Diseases 0.000 claims description 17
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
- 229940079593 drug Drugs 0.000 claims description 11
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical compound C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 8
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 230000002265 prevention Effects 0.000 claims description 8
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 5
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 150000001340 alkali metals Chemical class 0.000 claims description 5
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 5
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 5
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 2
- 238000003776 cleavage reaction Methods 0.000 abstract description 11
- 230000007017 scission Effects 0.000 abstract description 11
- 239000003696 aspartic proteinase inhibitor Substances 0.000 abstract description 9
- 150000003863 ammonium salts Chemical class 0.000 abstract description 8
- 125000003277 amino group Chemical group 0.000 abstract description 7
- 101710110426 Aspartyl protease inhibitor Proteins 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 68
- 238000002360 preparation method Methods 0.000 description 62
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 46
- 239000000243 solution Substances 0.000 description 41
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 36
- 239000000203 mixture Substances 0.000 description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- 235000019439 ethyl acetate Nutrition 0.000 description 27
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 27
- 235000002639 sodium chloride Nutrition 0.000 description 25
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 108010017640 Aspartic Acid Proteases Proteins 0.000 description 21
- 102000004580 Aspartic Acid Proteases Human genes 0.000 description 21
- 238000000034 method Methods 0.000 description 21
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- 241000725303 Human immunodeficiency virus Species 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 229910001868 water Inorganic materials 0.000 description 18
- QAHLFXYLXBBCPS-IZEXYCQBSA-N methyl n-[(2s)-1-[[(5s)-5-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-6-hydroxyhexyl]amino]-1-oxo-3,3-diphenylpropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C([C@H](NC(=O)OC)C(=O)NCCCC[C@@H](CO)N(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)C1=CC=CC=C1 QAHLFXYLXBBCPS-IZEXYCQBSA-N 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 239000004480 active ingredient Substances 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- 239000003921 oil Substances 0.000 description 14
- 235000019198 oils Nutrition 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- 229910019142 PO4 Inorganic materials 0.000 description 13
- 235000021317 phosphate Nutrition 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 12
- 239000004030 hiv protease inhibitor Substances 0.000 description 12
- 239000010452 phosphate Substances 0.000 description 12
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 12
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 11
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 11
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 10
- LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 235000018977 lysine Nutrition 0.000 description 10
- 230000003612 virological effect Effects 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 241000700605 Viruses Species 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 102000035195 Peptidases Human genes 0.000 description 8
- 108091005804 Peptidases Proteins 0.000 description 8
- 239000004365 Protease Substances 0.000 description 8
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 8
- 239000003981 vehicle Substances 0.000 description 8
- 208000030507 AIDS Diseases 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 239000007832 Na2SO4 Substances 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000002671 adjuvant Substances 0.000 description 7
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 7
- 239000012467 final product Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- RPKWYMFQSOJXIC-HVNZXBJASA-N methyl n-[(2s)-1-[[(5s)-5-[(4-amino-3-fluorophenyl)sulfonyl-(2-methylpropyl)amino]-6-phosphonooxyhexyl]amino]-1-oxo-3,3-diphenylpropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C([C@H](NC(=O)OC)C(=O)NCCCC[C@@H](COP(O)(O)=O)N(CC(C)C)S(=O)(=O)C=1C=C(F)C(N)=CC=1)C1=CC=CC=C1 RPKWYMFQSOJXIC-HVNZXBJASA-N 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
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- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 6
- KHASNRBNVBIREH-IZEXYCQBSA-N methyl n-[(2s)-1-[[(5s)-5-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-6-phosphonooxyhexyl]amino]-1-oxo-3,3-diphenylpropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C([C@H](NC(=O)OC)C(=O)NCCCC[C@@H](COP(O)(O)=O)N(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)C1=CC=CC=C1 KHASNRBNVBIREH-IZEXYCQBSA-N 0.000 description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
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- RIJQIRGRSFUUGK-IBGZPJMESA-N [(2s)-6-amino-2-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]hexyl] diethyl phosphate Chemical compound CCOP(=O)(OCC)OC[C@H](CCCCN)N(CC(C)C)S(=O)(=O)C1=CC=C(N)C=C1 RIJQIRGRSFUUGK-IBGZPJMESA-N 0.000 description 5
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- 239000008346 aqueous phase Substances 0.000 description 5
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
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- 229960002555 zidovudine Drugs 0.000 description 5
- 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 5
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- 238000004679 31P NMR spectroscopy Methods 0.000 description 4
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- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
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- 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 4
- FQXDPHCIZNWEHW-SPQRWCIKSA-N [(2S)-2-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-6-[[2-(methoxycarbonylamino)-3,3-diphenylpropanoyl]amino]hexyl] (2S)-2-amino-3-methylbutanoate Chemical compound NC1=CC=C(C=C1)S(=O)(=O)N([C@H](COC([C@H](C(C)C)N)=O)CCCCNC(C(C(C1=CC=CC=C1)C1=CC=CC=C1)NC(=O)OC)=O)CC(C)C FQXDPHCIZNWEHW-SPQRWCIKSA-N 0.000 description 4
- LBTVXRJLQXXNFU-JUKUECOXSA-N [(2s)-2-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-6-[[(2s)-2-(methoxycarbonylamino)-3,3-diphenylpropanoyl]amino]hexyl] pyridine-3-carboxylate Chemical compound C=1C=CC=CC=1C([C@H](NC(=O)OC)C(=O)NCCCC[C@@H](COC(=O)C=1C=NC=CC=1)N(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)C1=CC=CC=C1 LBTVXRJLQXXNFU-JUKUECOXSA-N 0.000 description 4
- XHXSMFOQXRRABL-NYDCQLBNSA-N [(2s)-2-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-6-[[(2s)-2-(morpholine-4-carbonylamino)-3-naphthalen-1-ylpropanoyl]amino]hexyl] dihydrogen phosphate Chemical compound N([C@@H](CC=1C2=CC=CC=C2C=CC=1)C(=O)NCCCC[C@H](N(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)COP(O)(O)=O)C(=O)N1CCOCC1 XHXSMFOQXRRABL-NYDCQLBNSA-N 0.000 description 4
- FSXWQRBPKBCDDM-NYDCQLBNSA-N [(2s)-6-[[(2s)-2-acetamido-3,3-diphenylpropanoyl]amino]-2-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]hexyl] dihydrogen phosphate Chemical compound C=1C=CC=CC=1C([C@H](NC(C)=O)C(=O)NCCCC[C@H](N(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)COP(O)(O)=O)C1=CC=CC=C1 FSXWQRBPKBCDDM-NYDCQLBNSA-N 0.000 description 4
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- SCWIUHICGSPBKM-VIFPVBQESA-N (3s)-3-(2-methylpropylamino)azepan-2-one Chemical compound CC(C)CN[C@H]1CCCCNC1=O SCWIUHICGSPBKM-VIFPVBQESA-N 0.000 description 3
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 3
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 3
- 241000598436 Human T-cell lymphotropic virus Species 0.000 description 3
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- 102000006992 Interferon-alpha Human genes 0.000 description 3
- 108010047761 Interferon-alpha Proteins 0.000 description 3
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
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- RMLUKZWYIKEASN-UHFFFAOYSA-M sodium;2-amino-9-(2-hydroxyethoxymethyl)purin-6-olate Chemical compound [Na+].O=C1[N-]C(N)=NC2=C1N=CN2COCCO RMLUKZWYIKEASN-UHFFFAOYSA-M 0.000 description 1
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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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 1
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- YFNGWGVTFYSJHE-UHFFFAOYSA-K trisodium;phosphonoformate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)C([O-])=O.OP(O)(=O)C([O-])=O.OP(O)(=O)C([O-])=O YFNGWGVTFYSJHE-UHFFFAOYSA-K 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
- C07C311/38—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton
- C07C311/39—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/41—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms, not being part of nitro or nitroso groups
-
- 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
- A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
-
- 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
- A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
- A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/091—Esters of phosphoric acids with hydroxyalkyl compounds with further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
- C07F9/6533—Six-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Biochemistry (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/CA2004/001440 WO2006012725A1 (en) | 2004-08-02 | 2004-08-02 | Lysine based compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2560071A1 CA2560071A1 (en) | 2006-02-09 |
| CA2560071C true CA2560071C (en) | 2012-09-25 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2560071A Expired - Fee Related CA2560071C (en) | 2004-08-02 | 2004-08-02 | Lysine based compounds |
Country Status (14)
| Country | Link |
|---|---|
| EP (2) | EP1773763B1 (enExample) |
| JP (1) | JP4579970B2 (enExample) |
| CN (1) | CN1942436B (enExample) |
| AT (1) | ATE417823T1 (enExample) |
| AU (2) | AU2004322123B2 (enExample) |
| BR (1) | BRPI0418651A (enExample) |
| CA (1) | CA2560071C (enExample) |
| DE (1) | DE602004018548D1 (enExample) |
| ES (2) | ES2575871T3 (enExample) |
| IL (1) | IL180958A0 (enExample) |
| MX (1) | MX2007001278A (enExample) |
| NO (1) | NO20071152L (enExample) |
| RU (1) | RU2009139259A (enExample) |
| WO (1) | WO2006012725A1 (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7388008B2 (en) | 2004-08-02 | 2008-06-17 | Ambrilia Biopharma Inc. | Lysine based compounds |
| ES2575871T3 (es) | 2004-08-02 | 2016-07-01 | Ambrilia Biopharma Inc. | Composiciones farmacéuticas que comprende un compuesto a base de lisina y un agente antiviral o antirretroviral VIH |
| EP1971615B1 (en) * | 2005-11-30 | 2014-01-01 | TaiMed Biologics, Inc. | Lysme-based prodrugs of aspartyl protease inhibitors and processes for their preparation |
| JP2010502569A (ja) * | 2006-07-17 | 2010-01-28 | アンブリリア バイオファーマ インコーポレイテッド | 薬物動態学の改善方法 |
| EP2064177B1 (en) | 2006-09-21 | 2017-04-05 | TaiMed Biologics, Inc. | Protease inhibitors |
| WO2009148600A2 (en) * | 2008-06-06 | 2009-12-10 | Concert Pharmaceuticals, Inc. | Deuterated lysine-based compounds |
| EP2435037B1 (en) | 2009-05-27 | 2014-11-12 | Merck Sharp & Dohme Corp. | Hiv protease inhibitors |
| US9079834B2 (en) | 2010-10-28 | 2015-07-14 | Merck Canada Inc. | HIV protease inhibitors |
| EP2632908B1 (en) | 2010-10-29 | 2016-05-25 | Merck Canada Inc. | Sulfonamides as hiv protease inhibitors |
| US9133157B2 (en) | 2011-10-26 | 2015-09-15 | Merck Canada Inc. | HIV protease inhibitors |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6436989B1 (en) * | 1997-12-24 | 2002-08-20 | Vertex Pharmaceuticals, Incorporated | Prodrugs of aspartyl protease inhibitors |
| CA2405151A1 (en) * | 2000-04-07 | 2001-10-18 | University Of Maryland, Baltimore | Bile acid containing prodrugs with enhanced bioavailability |
| US6617310B2 (en) * | 2000-07-19 | 2003-09-09 | Bristol-Myers Squibb Pharma Company | Phosphate esters of bis-amino acid sulfonamides containing substituted benzyl amines |
| JP2004517045A (ja) * | 2000-08-18 | 2004-06-10 | ザ ボード オブ トラスティーズ オブ ザ ユニバーシティ オブ イリノイ | 癌およびｈｉｖの治療用ベツリン酸誘導体のプロドラッグ |
| US6506786B2 (en) * | 2001-02-13 | 2003-01-14 | Pharmacor Inc. | HIV protease inhibitors based on amino acid derivatives |
| US6632816B1 (en) * | 2002-12-23 | 2003-10-14 | Pharmacor Inc. | Aromatic derivatives as HIV aspartyl protease inhibitors |
| ES2575871T3 (es) | 2004-08-02 | 2016-07-01 | Ambrilia Biopharma Inc. | Composiciones farmacéuticas que comprende un compuesto a base de lisina y un agente antiviral o antirretroviral VIH |
-
2004
- 2004-08-02 ES ES08021798.7T patent/ES2575871T3/es not_active Expired - Lifetime
- 2004-08-02 MX MX2007001278A patent/MX2007001278A/es active IP Right Grant
- 2004-08-02 BR BRPI0418651-6A patent/BRPI0418651A/pt not_active IP Right Cessation
- 2004-08-02 WO PCT/CA2004/001440 patent/WO2006012725A1/en not_active Ceased
- 2004-08-02 EP EP04761606A patent/EP1773763B1/en not_active Expired - Lifetime
- 2004-08-02 CA CA2560071A patent/CA2560071C/en not_active Expired - Fee Related
- 2004-08-02 ES ES04761606T patent/ES2319996T3/es not_active Expired - Lifetime
- 2004-08-02 EP EP08021798.7A patent/EP2165709B1/en not_active Expired - Lifetime
- 2004-08-02 JP JP2007501073A patent/JP4579970B2/ja not_active Expired - Fee Related
- 2004-08-02 AU AU2004322123A patent/AU2004322123B2/en not_active Ceased
- 2004-08-02 AT AT04761606T patent/ATE417823T1/de not_active IP Right Cessation
- 2004-08-02 DE DE602004018548T patent/DE602004018548D1/de not_active Expired - Lifetime
- 2004-08-02 CN CN2004800427980A patent/CN1942436B/zh not_active Expired - Fee Related
-
2007
- 2007-01-25 IL IL180958A patent/IL180958A0/en unknown
- 2007-03-01 NO NO20071152A patent/NO20071152L/no not_active Application Discontinuation
-
2009
- 2009-10-23 RU RU2009139259/04A patent/RU2009139259A/ru not_active Application Discontinuation
- 2009-10-28 AU AU2009230800A patent/AU2009230800A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP2165709B1 (en) | 2016-03-16 |
| NO20071152L (no) | 2007-03-01 |
| CA2560071A1 (en) | 2006-02-09 |
| EP1773763A4 (en) | 2007-08-08 |
| EP2165709A2 (en) | 2010-03-24 |
| IL180958A0 (en) | 2007-07-04 |
| JP4579970B2 (ja) | 2010-11-10 |
| EP1773763B1 (en) | 2008-12-17 |
| MX2007001278A (es) | 2007-09-14 |
| CN1942436B (zh) | 2011-03-23 |
| EP2165709A3 (en) | 2010-06-23 |
| DE602004018548D1 (de) | 2009-01-29 |
| RU2009139259A (ru) | 2011-04-27 |
| AU2004322123A1 (en) | 2006-02-09 |
| BRPI0418651A (pt) | 2007-05-29 |
| EP1773763A1 (en) | 2007-04-18 |
| AU2009230800A1 (en) | 2009-11-19 |
| WO2006012725A1 (en) | 2006-02-09 |
| AU2004322123B2 (en) | 2009-08-13 |
| CN1942436A (zh) | 2007-04-04 |
| HK1105406A1 (en) | 2008-02-15 |
| ES2575871T3 (es) | 2016-07-01 |
| ATE417823T1 (de) | 2009-01-15 |
| JP2007525527A (ja) | 2007-09-06 |
| ES2319996T3 (es) | 2009-05-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20150803 |