DE60215623T2 - Breitspektrum 2-(substituierte-amino)-benzothiazol-sulfonamide hiv protease inhibitoren - Google Patents
Breitspektrum 2-(substituierte-amino)-benzothiazol-sulfonamide hiv protease inhibitoren Download PDFInfo
- Publication number
- DE60215623T2 DE60215623T2 DE60215623T DE60215623T DE60215623T2 DE 60215623 T2 DE60215623 T2 DE 60215623T2 DE 60215623 T DE60215623 T DE 60215623T DE 60215623 T DE60215623 T DE 60215623T DE 60215623 T2 DE60215623 T2 DE 60215623T2
- Authority
- DE
- Germany
- Prior art keywords
- alkyl
- het
- aryl
- amino
- 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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- -1 2- (SUBSTITUTED AMINO) -BENZOTHIAZOLE-SULFONAMIDE Chemical class 0.000 title claims description 99
- 239000004030 hiv protease inhibitor Substances 0.000 title description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 292
- 150000001875 compounds Chemical class 0.000 claims description 217
- 239000000543 intermediate Substances 0.000 claims description 150
- 125000003118 aryl group Chemical group 0.000 claims description 94
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 69
- 239000000203 mixture Substances 0.000 claims description 62
- 229910052739 hydrogen Inorganic materials 0.000 claims description 61
- 239000001257 hydrogen Substances 0.000 claims description 61
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 56
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 53
- 150000002431 hydrogen Chemical class 0.000 claims description 43
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 40
- 239000003814 drug Substances 0.000 claims description 39
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 38
- 125000001424 substituent group Chemical group 0.000 claims description 36
- 125000003277 amino group Chemical group 0.000 claims description 33
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 32
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 28
- 238000002360 preparation method Methods 0.000 claims description 28
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 229940079593 drug Drugs 0.000 claims description 26
- 150000002367 halogens Chemical class 0.000 claims description 26
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 24
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 23
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 17
- 241001430294 unidentified retrovirus Species 0.000 claims description 17
- 125000004043 oxo group Chemical group O=* 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
- 241000700605 Viruses Species 0.000 claims description 15
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000004104 aryloxy group Chemical group 0.000 claims description 12
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 238000004519 manufacturing process Methods 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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 150000001204 N-oxides Chemical class 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 208000015181 infectious disease Diseases 0.000 claims description 9
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 8
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
- 125000002619 bicyclic group Chemical group 0.000 claims description 8
- 125000000169 tricyclic heterocycle group Chemical group 0.000 claims description 8
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 7
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 6
- 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
- 241000124008 Mammalia Species 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
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 6
- 101100219283 Amycolatopsis orientalis cyp165C4 gene Proteins 0.000 claims description 5
- 108091005804 Peptidases Proteins 0.000 claims description 5
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 239000004365 Protease Substances 0.000 claims description 4
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 4
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 4
- 125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 4
- 125000005200 aryloxy carbonyloxy group Chemical group 0.000 claims description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
- 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 4
- 230000008569 process Effects 0.000 claims description 4
- 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
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical class C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 3
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000005843 halogen group Chemical group 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
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- KRLZUGUOORSXFA-UHFFFAOYSA-N oxolan-3-yl n-[4-[[2-[2-(dimethylamino)ethylamino]-1,3-benzothiazol-6-yl]sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate Chemical compound C=1C=C2N=C(NCCN(C)C)SC2=CC=1S(=O)(=O)N(CC(C)C)CC(O)C(NC(=O)OC1COCC1)CC1=CC=CC=C1 KRLZUGUOORSXFA-UHFFFAOYSA-N 0.000 claims 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 2
- CSOOJXHGLYGRJL-UHFFFAOYSA-N 2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl n-[4-[[2-[(1-ethylpyrrolidin-2-yl)methylamino]-1,3-benzothiazol-6-yl]sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate Chemical compound CCN1CCCC1CNC1=NC2=CC=C(S(=O)(=O)N(CC(C)C)CC(O)C(CC=3C=CC=CC=3)NC(=O)OC3C4CCOC4OC3)C=C2S1 CSOOJXHGLYGRJL-UHFFFAOYSA-N 0.000 claims 1
- BIPRNLSSLKASRT-UHFFFAOYSA-N 2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl n-[4-[[2-[2-(dimethylamino)ethylamino]-1,3-benzothiazol-6-yl]sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate Chemical compound C=1C=C2N=C(NCCN(C)C)SC2=CC=1S(=O)(=O)N(CC(C)C)CC(O)C(NC(=O)OC1C2CCOC2OC1)CC1=CC=CC=C1 BIPRNLSSLKASRT-UHFFFAOYSA-N 0.000 claims 1
- HBJMMMAJSBLTMB-UHFFFAOYSA-N 2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl n-[4-[[2-[3-(dimethylamino)propyl-methylamino]-1,3-benzothiazol-6-yl]sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate 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)OC1C2CCOC2OC1)CC1=CC=CC=C1 HBJMMMAJSBLTMB-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
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 222
- 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 57
- 239000000243 solution Substances 0.000 description 54
- 239000002904 solvent Substances 0.000 description 45
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 239000011541 reaction mixture Substances 0.000 description 33
- 238000004949 mass spectrometry Methods 0.000 description 29
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 230000000694 effects Effects 0.000 description 21
- 239000012074 organic phase Substances 0.000 description 19
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- 230000002829 reductive effect Effects 0.000 description 16
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 15
- 0 CC(*)C(*)(N(C)*)O Chemical compound CC(*)C(*)(N(C)*)O 0.000 description 14
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 13
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 13
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
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- 150000003254 radicals Chemical class 0.000 description 12
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 11
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- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
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- 238000004587 chromatography analysis Methods 0.000 description 9
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 8
- 208000030507 AIDS Diseases 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 230000036436 anti-hiv Effects 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
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- 210000004027 cell Anatomy 0.000 description 8
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- 230000000144 pharmacologic effect Effects 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 229940124522 antiretrovirals Drugs 0.000 description 7
- 239000000126 substance Substances 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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- 239000003903 antiretrovirus agent Substances 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
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- 150000007513 acids Chemical class 0.000 description 5
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- 125000004429 atom Chemical group 0.000 description 5
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- 238000002953 preparative HPLC Methods 0.000 description 5
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- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 4
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- 101000898643 Candida albicans Vacuolar aspartic protease Proteins 0.000 description 4
- 101000898783 Candida tropicalis Candidapepsin Proteins 0.000 description 4
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- 108010010369 HIV Protease Proteins 0.000 description 4
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- 101000910088 Rhizopus niveus Rhizopuspepsin-5 Proteins 0.000 description 4
- 101000898773 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Saccharopepsin Proteins 0.000 description 4
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- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
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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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (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 (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01200529 | 2001-02-14 | ||
| EP01200529 | 2001-02-14 | ||
| US28775801P | 2001-05-02 | 2001-05-02 | |
| US287758P | 2001-05-02 | ||
| PCT/EP2002/001788 WO2002083657A2 (en) | 2001-02-14 | 2002-02-14 | Broadspectrum 2-(substituted-amino)-benzothiazole sulfonamide hiv protease inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60215623D1 DE60215623D1 (de) | 2006-12-07 |
| DE60215623T2 true DE60215623T2 (de) | 2007-08-30 |
Family
ID=26076833
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60215623T Expired - Lifetime DE60215623T2 (de) | 2001-02-14 | 2002-02-14 | Breitspektrum 2-(substituierte-amino)-benzothiazol-sulfonamide hiv protease inhibitoren |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US7659404B2 (https=) |
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| WO (1) | WO2002083657A2 (https=) |
| ZA (1) | ZA200306086B (https=) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MXPA01012270A (es) | 1999-05-28 | 2003-06-24 | Virco Nv | Nuevos perfiles mutacionales en la transcriptasa reversa de vih-1 correlacionadas con resistencia fenotipica a farmacos. |
| EP1356082A2 (en) | 2000-10-20 | 2003-10-29 | Virco Bvba | Mutational profiles in hiv-1 reverse transcriptase correlated with phenotypic drug resistance |
| ES2275866T3 (es) | 2001-02-14 | 2007-06-16 | Tibotec Pharmaceuticals Ltd. | 2-(aminosustituido)-benzotiazol-sulfonamidas de amplio esprecto inhibidoras de la proteasa de vih. |
| AU2003202914A1 (en) | 2002-01-07 | 2003-07-24 | Sequoia Pharmaceuticals | Broad spectrum inhibitors |
| US7157489B2 (en) | 2002-03-12 | 2007-01-02 | The Board Of Trustees Of The University Of Illinois | HIV protease inhibitors |
| US7217506B2 (en) | 2002-07-01 | 2007-05-15 | Tibotec Pharmaceuticals, Ltd. | Mutational profiles in HIV-1 protease correlated with phenotypic protease inhibitor resistance |
| AU2003251732B2 (en) | 2002-07-01 | 2008-09-18 | Tibotec Pharmaceuticals Ltd. | New mutational profiles in HIV-1 reverse transcriptase correlated with phenotypic drug resistance |
| KR101327772B1 (ko) * | 2002-08-02 | 2013-11-11 | 얀센 알 앤드 디 아일랜드 | 광범위 2-아미노-벤조티아졸 설폰아미드 ｈｉｖ 프로테아제 저해제 |
| PL374948A1 (en) * | 2002-08-02 | 2005-11-14 | Tibotec Pharmaceuticals Ltd. | Broadspectrum 2-amino-benzothiazole sulfonamide hiv protease inhibitors |
| JP4919802B2 (ja) * | 2003-09-30 | 2012-04-18 | テイボテク・フアーマシユーチカルズ | ベンゾオキサゾールスルホンアミド化合物およびその中間体の製造方法 |
| DE10360835A1 (de) * | 2003-12-23 | 2005-07-21 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclische Imidazolverbindungen, deren Herstellung und deren Verwendung als Arzneimittel |
| EP2422781A1 (en) * | 2004-05-07 | 2012-02-29 | Sequoia Pharmaceuticals, Inc. | Resistance-repellent retroviral protease inhibitors |
| RU2421459C2 (ru) | 2005-02-25 | 2011-06-20 | Тиботек Фармасьютикалз Лтд. | Синтез предшественника ингибитора протеазы |
| AR053845A1 (es) | 2005-04-15 | 2007-05-23 | Tibotec Pharm Ltd | 5-tiazolilmetil[(1s,2r)-3-[[(2-amino-6-benzoxazolil)sulfonil)](2-metilpropil)amino]-2-hidroxi-1-(fenilmetil)propil]carbamato como mejorador de farmacos metabolizados por el citocromo p450 |
| JO2841B1 (en) | 2006-06-23 | 2014-09-15 | تيبوتيك فارماسيوتيكالز ليمتد | 2-(substituted-amino) -benzothiazole sulfonamide as protease inhibitors HIV (HIV) |
| WO2011061590A1 (en) | 2009-11-17 | 2011-05-26 | Hetero Research Foundation | Novel carboxamide derivatives as hiv inhibitors |
| JO3090B1 (ar) * | 2009-12-11 | 2017-03-15 | Janssen Sciences Ireland Uc | 5- امينو-4- هيدروكسي-بنتويل اميدات |
| US9024038B2 (en) * | 2010-12-27 | 2015-05-05 | Purdue Research Foundation | Compunds and methods for treating HIV |
| ES2571479T3 (es) | 2012-04-20 | 2016-05-25 | Gilead Sciences Inc | Derivados del ácido benzotiazol-6-il acético y su uso para tratar una infección por VIH |
| CN104000824B (zh) * | 2014-05-28 | 2016-07-06 | 中山大学 | 苯并五元杂环类化合物在制备抗hiv-1病毒药物中的应用 |
| US11439608B2 (en) | 2017-09-25 | 2022-09-13 | Qun Lu | Roles of modulators of intersectin-CDC42 signaling in Alzheimer's disease |
| CN116354903B (zh) * | 2021-12-28 | 2025-09-09 | 南京药石科技股份有限公司 | 一种6-苯并噻唑磺酰氯的制备方法 |
| EP4676475A1 (en) * | 2023-03-24 | 2026-01-14 | Purdue Research Foundation | Hiv-1p rotease inhibitors and uses thereof |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0445926B1 (en) | 1990-03-09 | 1996-08-21 | Milliken Research Corporation | Organic materials having sulfonamido linked poly(oxyalkylene) moieties and their preparation |
| US5145684A (en) | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
| ATE218541T1 (de) | 1992-08-25 | 2002-06-15 | Searle & Co | Hydroxyethylaminosulfonamide verwendbar als inhibitoren retroviraler proteasen |
| PH30929A (en) | 1992-09-03 | 1997-12-23 | Janssen Pharmaceutica Nv | Beads having a core coated with an antifungal and a polymer. |
| IS2334B (is) * | 1992-09-08 | 2008-02-15 | Vertex Pharmaceuticals Inc., (A Massachusetts Corporation) | Aspartyl próteasi hemjari af nýjum flokki súlfonamíða |
| EP0715618B1 (en) * | 1993-08-24 | 1998-12-16 | G.D. Searle & Co. | Hydroxyethylamino sulphonamides useful as retroviral protease inhibitors |
| SK283569B6 (sk) | 1993-10-01 | 2003-09-11 | Astra Aktiebolag | Spôsob spracovania jemne deleného práškového liečiva, zariadenie na vykonávanie tohto spôsobu a aglomeráty vyrobené týmto spôsobom |
| US6143747A (en) | 1995-01-20 | 2000-11-07 | G. D. Searle & Co. | Bis-sulfonamide hydroxyethylamino retroviral protease inhibitors |
| US6140505A (en) * | 1995-03-10 | 2000-10-31 | G. D. Searle & Co. | Synthesis of benzo fused heterocyclic sulfonyl chlorides |
| US5756533A (en) * | 1995-03-10 | 1998-05-26 | G.D. Searle & Co. | Amino acid hydroxyethylamino sulfonamide retroviral protease inhibitors |
| US6150556A (en) * | 1995-03-10 | 2000-11-21 | G. D. Dearle & Co. | Bis-amino acid hydroxyethylamino sulfonamide retroviral protease inhibitors |
| US6861539B1 (en) * | 1995-03-10 | 2005-03-01 | G. D. Searle & Co. | Bis-amino acid hydroxyethylamino sulfonamide retroviral protease inhibitors |
| US5705500A (en) * | 1995-03-10 | 1998-01-06 | G.D. Searle & Co. | Sulfonylalkanoylamino hydroxyethylamino sulfonamide retroviral protease inhibitors |
| CN1530372A (zh) | 1995-03-10 | 2004-09-22 | G.D.ɪ����˾ | 杂环羰基氨基酸羟乙氨基磺酰胺逆转录病毒蛋白酶抑制剂 |
| US6143788A (en) * | 1995-03-10 | 2000-11-07 | G.D. Searle & Co. | Bis-amino acid hydroxyethlamino sulfonamide retroviral protease inhibitors |
| AU7722296A (en) | 1995-11-15 | 1997-06-05 | G.D. Searle & Co. | Substituted sulfonylalkanoylamino hydroxyethylamino sulfonamide retroviral protease inhibitors |
| ATE255883T1 (de) | 1996-05-20 | 2003-12-15 | Janssen Pharmaceutica Nv | Fungizide mittel mit verbesserter bioverfügbarkeit |
| JP3608800B2 (ja) | 1997-03-26 | 2005-01-12 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 抗真菌剤およびポリマーでコートされたコアを有するペレット剤 |
| WO1999033792A2 (en) | 1997-12-24 | 1999-07-08 | Vertex Pharmaceuticals Incorporated | Prodrugs os aspartyl protease inhibitors |
| US6436989B1 (en) | 1997-12-24 | 2002-08-20 | Vertex Pharmaceuticals, Incorporated | Prodrugs of aspartyl protease inhibitors |
| EE200000386A (et) | 1997-12-24 | 2001-12-17 | Vertex Pharmaceuticals Incorporated | Aspartüülproteaasi inhibiitorite eelravimid |
| AU2012199A (en) | 1997-12-24 | 1999-07-19 | Vertex Pharmaceuticals Incorporated | Prodrugs of aspartyl protease inhibitors |
| BR9912169A (pt) * | 1998-06-19 | 2001-04-10 | Vertex Pharma | Inibidores de sulfonamida de protease de aspartil |
| WO1999067254A2 (en) | 1998-06-23 | 1999-12-29 | The United States Of America Represented By The Secretary, Department Of Health And Human Services | Multi-drug resistant retroviral protease inhibitors and use thereof |
| PT2336134T (pt) | 1998-06-23 | 2016-10-19 | The Board Of Trustees Of The Univ Of Illionis | Ensaio de aptidão e métodos para reduzir a resistência do hiv à terapia |
| AR031520A1 (es) * | 1999-06-11 | 2003-09-24 | Vertex Pharma | Un compuesto inhibidor de aspartilo proteasa, una composicion que lo comprende y un metodo para tratar un paciente con dicha composicion |
| ES2275866T3 (es) | 2001-02-14 | 2007-06-16 | Tibotec Pharmaceuticals Ltd. | 2-(aminosustituido)-benzotiazol-sulfonamidas de amplio esprecto inhibidoras de la proteasa de vih. |
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