ES2275866T3 - 2-(aminosustituido)-benzotiazol-sulfonamidas de amplio esprecto inhibidoras de la proteasa de vih. - Google Patents
2-(aminosustituido)-benzotiazol-sulfonamidas de amplio esprecto inhibidoras de la proteasa de vih. Download PDFInfo
- Publication number
- ES2275866T3 ES2275866T3 ES02729930T ES02729930T ES2275866T3 ES 2275866 T3 ES2275866 T3 ES 2275866T3 ES 02729930 T ES02729930 T ES 02729930T ES 02729930 T ES02729930 T ES 02729930T ES 2275866 T3 ES2275866 T3 ES 2275866T3
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- Spain
- Prior art keywords
- alkyl
- het
- aryl
- compound
- cycloalkyl
- 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 - Lifetime
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- 108091005804 Peptidases Proteins 0.000 title claims description 10
- 239000004365 Protease Substances 0.000 title claims description 9
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 title claims description 9
- 229940124530 sulfonamide Drugs 0.000 title description 8
- 230000002401 inhibitory effect Effects 0.000 title description 4
- 235000015096 spirit Nutrition 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 352
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 283
- 125000003118 aryl group Chemical group 0.000 claims abstract description 105
- -1 C1- aryl alkyl 6 Chemical group 0.000 claims abstract description 97
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 82
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 64
- 239000001257 hydrogen Substances 0.000 claims abstract description 64
- 239000000203 mixture Substances 0.000 claims abstract description 61
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 54
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 49
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 48
- 125000003277 amino group Chemical group 0.000 claims abstract description 39
- 125000001424 substituent group Chemical group 0.000 claims abstract description 38
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 32
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 27
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 27
- 150000002367 halogens Chemical class 0.000 claims abstract description 27
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 19
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 18
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims abstract description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 15
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 14
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims abstract description 14
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 13
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims abstract description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 12
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 9
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- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims abstract description 6
- 125000005199 aryl carbonyloxy group Chemical group 0.000 claims abstract description 5
- 125000005200 aryloxy carbonyloxy group Chemical group 0.000 claims abstract description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 55
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 47
- 150000002431 hydrogen Chemical class 0.000 claims description 46
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- 238000000034 method Methods 0.000 claims description 35
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- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 26
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 20
- 125000005429 oxyalkyl group Chemical group 0.000 claims description 19
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
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- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
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- 241001430294 unidentified retrovirus Species 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 239000011593 sulfur Substances 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- 125000002619 bicyclic group Chemical group 0.000 claims description 8
- 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
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- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
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- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 5
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
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- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 4
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 4
- 125000005201 cycloalkylcarbonyloxy group Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 3
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
- FODOUIXGKGNSMR-UHFFFAOYSA-L magnesium;2-oxidooxycarbonylbenzoate;hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[O-]OC(=O)C1=CC=CC=C1C([O-])=O FODOUIXGKGNSMR-UHFFFAOYSA-L 0.000 claims description 3
- 230000010076 replication Effects 0.000 claims description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 2
- 206010061598 Immunodeficiency Diseases 0.000 claims description 2
- 208000029462 Immunodeficiency disease Diseases 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 230000007813 immunodeficiency Effects 0.000 claims description 2
- 125000000169 tricyclic heterocycle group Chemical group 0.000 claims description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims 2
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims 2
- GSFNQBFZFXUTBN-UHFFFAOYSA-N 2-chlorothiophene Chemical compound ClC1=CC=CS1 GSFNQBFZFXUTBN-UHFFFAOYSA-N 0.000 claims 1
- MOPCVYGYIJCLEZ-UHFFFAOYSA-N [4-[[2-[3-(dimethylamino)propyl-methylamino]-1,3-benzothiazol-6-yl]sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamic acid Chemical compound C=1C=C2N=C(N(C)CCCN(C)C)SC2=CC=1S(=O)(=O)N(CC(C)C)CC(O)C(NC(O)=O)CC1=CC=CC=C1 MOPCVYGYIJCLEZ-UHFFFAOYSA-N 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 4
- 125000003107 substituted aryl group Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 219
- 239000000543 intermediate Chemical class 0.000 description 137
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 75
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- 239000000243 solution Substances 0.000 description 51
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- 241000725303 Human immunodeficiency virus Species 0.000 description 37
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- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 28
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 23
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 20
- 230000000694 effects Effects 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
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- 230000002829 reductive effect Effects 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
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- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- 239000000651 prodrug Substances 0.000 description 11
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
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- 230000036436 anti-hiv Effects 0.000 description 8
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 6
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- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical group O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 4
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- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
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- WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—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
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/82—Nitrogen atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
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| EP01200529 | 2001-02-14 | ||
| EP01200529 | 2001-02-14 | ||
| US28775801P | 2001-05-02 | 2001-05-02 | |
| US287758P | 2001-05-02 |
Publications (1)
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| ES2275866T3 true ES2275866T3 (es) | 2007-06-16 |
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| ES02729930T Expired - Lifetime ES2275866T3 (es) | 2001-02-14 | 2002-02-14 | 2-(aminosustituido)-benzotiazol-sulfonamidas de amplio esprecto inhibidoras de la proteasa de vih. |
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| BR (1) | BR0207862A (enExample) |
| CA (1) | CA2438304C (enExample) |
| CY (1) | CY1108073T1 (enExample) |
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| HR (1) | HRP20030735B1 (enExample) |
| HU (1) | HU229224B1 (enExample) |
| IL (2) | IL157171A0 (enExample) |
| MX (1) | MXPA03007236A (enExample) |
| NO (1) | NO326174B1 (enExample) |
| NZ (1) | NZ527391A (enExample) |
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| ZA (1) | ZA200306086B (enExample) |
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| WO2000073511A1 (en) | 1999-05-28 | 2000-12-07 | Virco Nv | New mutational profiles in hiv-1 reverse transcriptase correlated with phenotypic drug resistance |
| EP1356082A2 (en) | 2000-10-20 | 2003-10-29 | Virco Bvba | Mutational profiles in hiv-1 reverse transcriptase correlated with phenotypic drug resistance |
| ATE343567T1 (de) | 2001-02-14 | 2006-11-15 | Tibotec Pharm Ltd | Breitspektrum 2-(substituierte-amino)- benzothiazol-sulfonamide hiv protease inhibitoren |
| US7109230B2 (en) | 2002-01-07 | 2006-09-19 | Sequoia Pharmaceuticals, Inc. | Resistance-repellent retroviral protease inhibitors |
| US7157489B2 (en) | 2002-03-12 | 2007-01-02 | The Board Of Trustees Of The University Of Illinois | HIV protease inhibitors |
| EP1520247B1 (en) | 2002-07-01 | 2009-05-27 | Tibotec Pharmaceuticals Ltd. | Mutational profiles in hiv-1 protease correlated with phenotypic drug resistance |
| WO2004003223A2 (en) | 2002-07-01 | 2004-01-08 | Tibotec Pharmaceuticals Ltd. | New mutational profiles in hiv-1 reverse transcriptase correlated with phenotypic drug resistance |
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