CZ298847B6 - Zpusob výroby proteázového inhibitoru - Google Patents
Zpusob výroby proteázového inhibitoru Download PDFInfo
- Publication number
- CZ298847B6 CZ298847B6 CZ20000804A CZ2000804A CZ298847B6 CZ 298847 B6 CZ298847 B6 CZ 298847B6 CZ 20000804 A CZ20000804 A CZ 20000804A CZ 2000804 A CZ2000804 A CZ 2000804A CZ 298847 B6 CZ298847 B6 CZ 298847B6
- Authority
- CZ
- Czechia
- Prior art keywords
- acid
- hydroxylactone
- formula
- phenyl
- hydroxy
- Prior art date
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- 238000004519 manufacturing process Methods 0.000 title claims abstract description 11
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 title abstract description 9
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title abstract description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 135
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 134
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 99
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 49
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 34
- 238000000034 method Methods 0.000 claims description 34
- 239000002253 acid Substances 0.000 claims description 30
- 238000002360 preparation method Methods 0.000 claims description 28
- -1 3-nitrophenyl Chemical group 0.000 claims description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
- 230000008569 process Effects 0.000 claims description 19
- 239000011541 reaction mixture Substances 0.000 claims description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 17
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- QUCVMTKZXVHNNT-CQSZACIVSA-N (3r)-3-hydroxy-3-(2-phenylethyl)hexanoic acid Chemical compound CCC[C@](O)(CC(O)=O)CCC1=CC=CC=C1 QUCVMTKZXVHNNT-CQSZACIVSA-N 0.000 claims description 9
- 229910021529 ammonia Inorganic materials 0.000 claims description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 7
- DLNKOYKMWOXYQA-CBAPKCEASA-N (-)-norephedrine Chemical compound C[C@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-CBAPKCEASA-N 0.000 claims description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 5
- 230000003213 activating effect Effects 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 229910052749 magnesium Inorganic materials 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 229960000281 trometamol Drugs 0.000 claims description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 3
- 239000012190 activator Substances 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- DLNKOYKMWOXYQA-VXNVDRBHSA-N (+)-norephedrine Chemical compound C[C@@H](N)[C@@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-VXNVDRBHSA-N 0.000 claims description 2
- RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 claims description 2
- RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 claims description 2
- IJXJGQCXFSSHNL-MRVPVSSYSA-N (2s)-2-amino-2-phenylethanol Chemical compound OC[C@@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-MRVPVSSYSA-N 0.000 claims description 2
- IJXJGQCXFSSHNL-UHFFFAOYSA-N 2-amino-2-phenylethanol Chemical compound OCC(N)C1=CC=CC=C1 IJXJGQCXFSSHNL-UHFFFAOYSA-N 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 4
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 claims 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 2
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims 2
- 229940106681 chloroacetic acid Drugs 0.000 claims 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims 2
- 229940071870 hydroiodic acid Drugs 0.000 claims 2
- 150000007522 mineralic acids Chemical class 0.000 claims 2
- 150000007524 organic acids Chemical class 0.000 claims 2
- 239000003495 polar organic solvent Substances 0.000 claims 2
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 claims 1
- JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims 1
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 claims 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 claims 1
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 claims 1
- 238000000605 extraction Methods 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 claims 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 claims 1
- 239000001120 potassium sulphate Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 claims 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 claims 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 claims 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 claims 1
- 241000725303 Human immunodeficiency virus Species 0.000 abstract description 5
- 239000000543 intermediate Substances 0.000 abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- 239000000203 mixture Substances 0.000 description 73
- 150000001875 compounds Chemical class 0.000 description 53
- 239000000243 solution Substances 0.000 description 35
- 239000000047 product Substances 0.000 description 23
- 239000002244 precipitate Substances 0.000 description 22
- 238000004809 thin layer chromatography Methods 0.000 description 22
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000012071 phase Substances 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- 238000003828 vacuum filtration Methods 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- 239000008346 aqueous phase Substances 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 238000007792 addition Methods 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- 239000007787 solid Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 6
- 230000009466 transformation Effects 0.000 description 6
- 208000030507 AIDS Diseases 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- LSEJDXFJBNGGBI-UHFFFAOYSA-N 1-(3-nitrophenyl)propan-1-ol Chemical compound CCC(O)C1=CC=CC([N+]([O-])=O)=C1 LSEJDXFJBNGGBI-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 239000000538 analytical sample Substances 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- PJKIILWMVXQSGH-UHFFFAOYSA-N 1-(bromomethylsulfanyl)-4-chlorobenzene Chemical compound ClC1=CC=C(SCBr)C=C1 PJKIILWMVXQSGH-UHFFFAOYSA-N 0.000 description 3
- GWMKCZGJHKWPFM-UHFFFAOYSA-N 1-(chloromethoxy)-4-phenylbenzene Chemical compound C1=CC(OCCl)=CC=C1C1=CC=CC=C1 GWMKCZGJHKWPFM-UHFFFAOYSA-N 0.000 description 3
- WSDRGQITBWEKQA-UHFFFAOYSA-N 1-chloro-4-[(4-phenylphenoxy)methylsulfanyl]benzene Chemical compound C1=CC(Cl)=CC=C1SCOC1=CC=C(C=2C=CC=CC=2)C=C1 WSDRGQITBWEKQA-UHFFFAOYSA-N 0.000 description 3
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 3
- DIYWMJFAVIYCGH-UHFFFAOYSA-N 6-propylpyran-2-one Chemical compound CCCC1=CC=CC(=O)O1 DIYWMJFAVIYCGH-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 150000001923 cyclic compounds Chemical class 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- LSEJDXFJBNGGBI-VIFPVBQESA-N (1s)-1-(3-nitrophenyl)propan-1-ol Chemical compound CC[C@H](O)C1=CC=CC([N+]([O-])=O)=C1 LSEJDXFJBNGGBI-VIFPVBQESA-N 0.000 description 2
- JOJIETQASLPADP-HHHXNRCGSA-N (3r)-3-(2-phenylethyl)-3-[(4-phenylphenoxy)methoxy]hexan-1-ol Chemical compound C([C@@](CCO)(CCC)OCOC=1C=CC(=CC=1)C=1C=CC=CC=1)CC1=CC=CC=C1 JOJIETQASLPADP-HHHXNRCGSA-N 0.000 description 2
- QWIVSBUSLLCPTK-HHHXNRCGSA-N (3r)-3-(2-phenylethyl)-3-[(4-phenylphenoxy)methoxy]hexanal Chemical compound C([C@](CCC)(CC=O)OCOC=1C=CC(=CC=1)C=1C=CC=CC=1)CC1=CC=CC=C1 QWIVSBUSLLCPTK-HHHXNRCGSA-N 0.000 description 2
- JDTSGYHXRDOSCX-QMMMGPOBSA-N (3s)-3-(3-nitrophenyl)pentanoic acid Chemical compound OC(=O)C[C@H](CC)C1=CC=CC([N+]([O-])=O)=C1 JDTSGYHXRDOSCX-QMMMGPOBSA-N 0.000 description 2
- RZIBXUTWMSXUBQ-RRHRGVEJSA-N (4-phenylphenoxy)methyl (3r)-3-(2-phenylethyl)-3-[(4-phenylphenoxy)methoxy]hexanoate Chemical compound C([C@](CCC)(CC(=O)OCOC=1C=CC(=CC=1)C=1C=CC=CC=1)OCOC=1C=CC(=CC=1)C=1C=CC=CC=1)CC1=CC=CC=C1 RZIBXUTWMSXUBQ-RRHRGVEJSA-N 0.000 description 2
- QUCVMTKZXVHNNT-UHFFFAOYSA-N 3-hydroxy-3-(2-phenylethyl)hexanoic acid Chemical compound CCCC(O)(CC(O)=O)CCC1=CC=CC=C1 QUCVMTKZXVHNNT-UHFFFAOYSA-N 0.000 description 2
- VZXOZSQDJJNBRC-UHFFFAOYSA-N 4-chlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1 VZXOZSQDJJNBRC-UHFFFAOYSA-N 0.000 description 2
- MRIFFPWOMKLYKZ-UHFFFAOYSA-N 5-(trifluoromethyl)pyridine-2-sulfonyl chloride Chemical compound FC(F)(F)C1=CC=C(S(Cl)(=O)=O)N=C1 MRIFFPWOMKLYKZ-UHFFFAOYSA-N 0.000 description 2
- NQHOCUSTYHHGRC-XVDYFQFQSA-N C(=O)(OC)C(C(CC)C1=CC(=CC=C1)[N+](=O)[O-])C(C[C@](CCC)(OCOC1=CC=C(C=C1)C1=CC=CC=C1)CCC1=CC=CC=C1)=O Chemical compound C(=O)(OC)C(C(CC)C1=CC(=CC=C1)[N+](=O)[O-])C(C[C@](CCC)(OCOC1=CC=C(C=C1)C1=CC=CC=C1)CCC1=CC=CC=C1)=O NQHOCUSTYHHGRC-XVDYFQFQSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- HCVUBIYUOHGTSH-JTQLQIEISA-N [(1s)-1-(3-nitrophenyl)propyl] methanesulfonate Chemical compound CS(=O)(=O)O[C@@H](CC)C1=CC=CC([N+]([O-])=O)=C1 HCVUBIYUOHGTSH-JTQLQIEISA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- YXVFYQXJAXKLAK-UHFFFAOYSA-N biphenyl-4-ol Chemical compound C1=CC(O)=CC=C1C1=CC=CC=C1 YXVFYQXJAXKLAK-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- QGGZBXOADPVUPN-UHFFFAOYSA-N dihydrochalcone Chemical compound C=1C=CC=CC=1C(=O)CCC1=CC=CC=C1 QGGZBXOADPVUPN-UHFFFAOYSA-N 0.000 description 2
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- JTDXSNGBXBTUKS-KQQRWUGMSA-N methyl (5r)-3-hydroxy-2-[1-(3-nitrophenyl)propyl]-5-(2-phenylethyl)-5-[(4-phenylphenoxy)methoxy]octanoate Chemical compound C([C@](CCC)(CC(O)C(C(CC)C=1C=C(C=CC=1)[N+]([O-])=O)C(=O)OC)OCOC=1C=CC(=CC=1)C=1C=CC=CC=1)CC1=CC=CC=C1 JTDXSNGBXBTUKS-KQQRWUGMSA-N 0.000 description 2
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- RCJVRSBWZCNNQT-UHFFFAOYSA-N dichloridooxygen Chemical compound ClOCl RCJVRSBWZCNNQT-UHFFFAOYSA-N 0.000 description 1
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- QDYBCIWLGJMJGO-UHFFFAOYSA-N dinitromethanone Chemical compound [O-][N+](=O)C(=O)[N+]([O-])=O QDYBCIWLGJMJGO-UHFFFAOYSA-N 0.000 description 1
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- PVCRXRJCJJIZJW-VIFPVBQESA-N methyl (3s)-3-(3-nitrophenyl)pentanoate Chemical compound COC(=O)C[C@H](CC)C1=CC=CC([N+]([O-])=O)=C1 PVCRXRJCJJIZJW-VIFPVBQESA-N 0.000 description 1
- PVCRXRJCJJIZJW-UHFFFAOYSA-N methyl 3-(3-nitrophenyl)pentanoate Chemical compound COC(=O)CC(CC)C1=CC=CC([N+]([O-])=O)=C1 PVCRXRJCJJIZJW-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
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- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 229960000395 phenylpropanolamine Drugs 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- WVUCPRGADMCTBN-UHFFFAOYSA-M potassium;3-ethoxy-3-oxopropanoate Chemical compound [K+].CCOC(=O)CC([O-])=O WVUCPRGADMCTBN-UHFFFAOYSA-M 0.000 description 1
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- 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
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- PODWXQQNRWNDGD-UHFFFAOYSA-L sodium thiosulfate pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[O-]S([S-])(=O)=O PODWXQQNRWNDGD-UHFFFAOYSA-L 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- JSPLKZUTYZBBKA-UHFFFAOYSA-N trioxidane Chemical compound OOO JSPLKZUTYZBBKA-UHFFFAOYSA-N 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/56—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups bound to carbon atoms of six-membered aromatic rings and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/30—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with halogen containing compounds, e.g. hypohalogenation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/20—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms
- C07C47/277—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/42—Unsaturated compounds containing hydroxy or O-metal groups
- C07C59/48—Unsaturated compounds containing hydroxy or O-metal groups containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/32—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrane Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pyridine Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5861897P | 1997-09-11 | 1997-09-11 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CZ2000804A3 CZ2000804A3 (cs) | 2000-08-16 |
| CZ298847B6 true CZ298847B6 (cs) | 2008-02-27 |
Family
ID=22017924
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ20000804A CZ298847B6 (cs) | 1997-09-11 | 1998-09-03 | Zpusob výroby proteázového inhibitoru |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US6077963A (enExample) |
| EP (1) | EP1015441B1 (enExample) |
| JP (3) | JP4462760B2 (enExample) |
| KR (1) | KR100569771B1 (enExample) |
| CN (3) | CN1284763C (enExample) |
| AT (1) | ATE266654T1 (enExample) |
| CA (1) | CA2300204C (enExample) |
| CZ (1) | CZ298847B6 (enExample) |
| DE (1) | DE69823844T2 (enExample) |
| DK (1) | DK1015441T3 (enExample) |
| ES (1) | ES2221199T3 (enExample) |
| FI (1) | FI120973B (enExample) |
| HU (1) | HU228986B1 (enExample) |
| NO (1) | NO321835B1 (enExample) |
| NZ (1) | NZ503338A (enExample) |
| PL (1) | PL193240B1 (enExample) |
| PT (1) | PT1015441E (enExample) |
| RU (2) | RU2223958C2 (enExample) |
| SK (1) | SK284974B6 (enExample) |
| WO (1) | WO1999012919A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2185582T3 (es) * | 1999-03-18 | 2003-05-01 | Upjohn Co | Procedimiento mejorado de hidrogenacion asimetrica. |
| US6552204B1 (en) * | 2000-02-04 | 2003-04-22 | Roche Colorado Corporation | Synthesis of 3,6-dialkyl-5,6-dihydro-4-hydroxy-pyran-2-one |
| US6500963B2 (en) | 2001-02-22 | 2002-12-31 | Boehringer Ingelheim Pharma Kg | Process for preparing optically active dihydropyrones |
| DE10108470A1 (de) * | 2001-02-22 | 2002-09-05 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung optisch aktiver Dihydropyrone |
| US6987123B2 (en) * | 2001-07-26 | 2006-01-17 | Cadila Healthcare Limited | Heterocyclic compounds, their preparation, pharmaceutical compositions containing them and their use in medicine |
| JP4108611B2 (ja) * | 2002-02-07 | 2008-06-25 | 住友化学株式会社 | （ｒ）−３−ヒドロキシ−３−（２−フェニルエチル）ヘキサン酸の製造方法 |
| DE10313118A1 (de) | 2003-03-24 | 2004-10-07 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Enantioselektive Hydrierung von Intermediaten bei der Tipranavir-Synthese |
| US7512945B2 (en) * | 2003-12-29 | 2009-03-31 | Intel Corporation | Method and apparatus for scheduling the processing of commands for execution by cryptographic algorithm cores in a programmable network processor |
| CN100448836C (zh) * | 2005-06-03 | 2009-01-07 | 浙江中贝化工有限公司 | 一种抗艾滋病药物关键中间体的制备方法 |
| US7807838B2 (en) * | 2005-08-24 | 2010-10-05 | Pfizer Inc. | Methods for the preparation of HCV polymerase inhibitors |
| KR101614103B1 (ko) * | 2007-11-30 | 2016-04-21 | 가부시키가이샤 한도오따이 에네루기 켄큐쇼 | 발광 소자, 발광 장치 및 전자기기 |
| US8853393B2 (en) * | 2011-07-29 | 2014-10-07 | Anhui New Star Pharmaceutical Development Co., Ltd. | Intermediate for preparing tapentadol or analogues thereof |
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| FR2096877A1 (enExample) * | 1970-07-09 | 1972-03-03 | Hexachimie | |
| WO1994011361A1 (en) * | 1992-11-13 | 1994-05-26 | The Upjohn Company | Pyran-2-ones and 5,6-dihydropyran-2-ones useful for treating hiv and other retroviruses |
| WO1995014012A1 (en) * | 1993-11-19 | 1995-05-26 | Parke, Davis & Company | 5,6-dihydropyrone derivatives as protease inhibitors and antiviral agents |
| WO1995030670A2 (en) * | 1994-05-06 | 1995-11-16 | Pharmacia & Upjohn Company | Pyranone compounds useful to treat retroviral infections |
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| FR1355667A (fr) * | 1963-02-05 | 1964-03-20 | Meci Materiel Elect Contr | Gaine tubulaire pour électrode servant à la mesure du ph |
| FR1355668A (fr) * | 1963-02-05 | 1964-03-20 | Moteur rotatif à combustion interne perfectionné | |
| JPH0665657B2 (ja) * | 1984-11-08 | 1994-08-24 | 日本化薬株式会社 | 光学活性マンデル酸の製法 |
| JPH072677B2 (ja) * | 1988-02-19 | 1995-01-18 | 株式会社クラレ | （±）―２―ヒドロキシ―４―フェニルブタン酸の光学分割法 |
| JPH01221345A (ja) * | 1988-02-27 | 1989-09-04 | Ajinomoto Co Inc | マンデル酸誘導体の光学分割方法 |
| JP3084577B2 (ja) * | 1991-09-27 | 2000-09-04 | 山川薬品工業株式会社 | 光学活性なアトロラクチン酸の製造方法および製造の中間体 |
| JP3178086B2 (ja) * | 1992-06-17 | 2001-06-18 | 山川薬品工業株式会社 | 光学活性α−メチルベンジルアミンの製造方法 |
| RU2074169C1 (ru) * | 1995-05-10 | 1997-02-27 | Акционерное общество открытого типа "Химпром" | Способ получения этилового эфира п-нитробензойной кислоты |
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1998
- 1998-09-03 RU RU2000109277/04A patent/RU2223958C2/ru active
- 1998-09-03 PL PL339138A patent/PL193240B1/pl unknown
- 1998-09-03 SK SK226-2000A patent/SK284974B6/sk not_active IP Right Cessation
- 1998-09-03 ES ES98945806T patent/ES2221199T3/es not_active Expired - Lifetime
- 1998-09-03 PT PT98945806T patent/PT1015441E/pt unknown
- 1998-09-03 CN CNB031594735A patent/CN1284763C/zh not_active Expired - Lifetime
- 1998-09-03 CN CNB988087111A patent/CN1298714C/zh not_active Expired - Lifetime
- 1998-09-03 AT AT98945806T patent/ATE266654T1/de active
- 1998-09-03 DK DK98945806T patent/DK1015441T3/da active
- 1998-09-03 CN CNB2007100079776A patent/CN100471832C/zh not_active Expired - Lifetime
- 1998-09-03 CZ CZ20000804A patent/CZ298847B6/cs not_active IP Right Cessation
- 1998-09-03 EP EP98945806A patent/EP1015441B1/en not_active Expired - Lifetime
- 1998-09-03 NZ NZ503338A patent/NZ503338A/en not_active IP Right Cessation
- 1998-09-03 JP JP2000510727A patent/JP4462760B2/ja not_active Expired - Lifetime
- 1998-09-03 HU HU0003593A patent/HU228986B1/hu unknown
- 1998-09-03 KR KR1020007002546A patent/KR100569771B1/ko not_active Expired - Lifetime
- 1998-09-03 CA CA002300204A patent/CA2300204C/en not_active Expired - Lifetime
- 1998-09-03 WO PCT/US1998/017993 patent/WO1999012919A1/en not_active Ceased
- 1998-09-03 DE DE69823844T patent/DE69823844T2/de not_active Expired - Lifetime
- 1998-12-17 US US09/213,887 patent/US6077963A/en not_active Expired - Lifetime
-
2000
- 2000-02-28 US US09/514,087 patent/US6265604B1/en not_active Expired - Lifetime
- 2000-03-10 NO NO20001274A patent/NO321835B1/no not_active IP Right Cessation
- 2000-03-10 FI FI20000553A patent/FI120973B/fi not_active IP Right Cessation
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2003
- 2003-10-21 RU RU2003131081/04A patent/RU2263106C2/ru active
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2009
- 2009-02-03 JP JP2009022289A patent/JP5016621B2/ja not_active Expired - Lifetime
- 2009-12-10 JP JP2009280318A patent/JP5266194B2/ja not_active Expired - Lifetime
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| FR2096877A1 (enExample) * | 1970-07-09 | 1972-03-03 | Hexachimie | |
| WO1994011361A1 (en) * | 1992-11-13 | 1994-05-26 | The Upjohn Company | Pyran-2-ones and 5,6-dihydropyran-2-ones useful for treating hiv and other retroviruses |
| WO1995014012A1 (en) * | 1993-11-19 | 1995-05-26 | Parke, Davis & Company | 5,6-dihydropyrone derivatives as protease inhibitors and antiviral agents |
| WO1995030670A2 (en) * | 1994-05-06 | 1995-11-16 | Pharmacia & Upjohn Company | Pyranone compounds useful to treat retroviral infections |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PD00 | Pending as of 2000-06-30 in czech republic | ||
| MK4A | Patent expired |
Effective date: 20180903 |