DE69321845T2 - Hydroxyethylaminosulfonamide verwendbar als inhibitoren retroviraler proteasen - Google Patents
Hydroxyethylaminosulfonamide verwendbar als inhibitoren retroviraler proteasenInfo
- Publication number
- DE69321845T2 DE69321845T2 DE69321845T DE69321845T DE69321845T2 DE 69321845 T2 DE69321845 T2 DE 69321845T2 DE 69321845 T DE69321845 T DE 69321845T DE 69321845 T DE69321845 T DE 69321845T DE 69321845 T2 DE69321845 T2 DE 69321845T2
- Authority
- DE
- Germany
- Prior art keywords
- radicals
- compound according
- amino
- hydrogen
- phenylmethyl
- 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
Links
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- 239000004365 Protease Substances 0.000 title claims abstract description 22
- 230000001177 retroviral effect Effects 0.000 title claims abstract description 19
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- 230000002401 inhibitory effect Effects 0.000 claims abstract description 12
- 108010010369 HIV Protease Proteins 0.000 claims abstract description 7
- 206010038997 Retroviral infections Diseases 0.000 claims abstract description 6
- 208000031886 HIV Infections Diseases 0.000 claims abstract description 5
- 208000030507 AIDS Diseases 0.000 claims abstract description 4
- 208000037357 HIV infectious disease Diseases 0.000 claims abstract description 4
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims abstract description 4
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- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 42
- 125000000217 alkyl group Chemical group 0.000 claims description 39
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
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- 229940121354 immunomodulator Drugs 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
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- 238000009776 industrial production Methods 0.000 description 1
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- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
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- MJGFBOZCAJSGQW-UHFFFAOYSA-N mercury sodium Chemical compound [Na].[Hg] MJGFBOZCAJSGQW-UHFFFAOYSA-N 0.000 description 1
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- 150000004692 metal hydroxides Chemical class 0.000 description 1
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- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 1
- OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
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- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- UQRORFVVSGFNRO-UTINFBMNSA-N miglustat Chemical compound CCCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO UQRORFVVSGFNRO-UTINFBMNSA-N 0.000 description 1
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- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
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- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- XURVRZSODRHRNK-UHFFFAOYSA-N o-quinodimethane Chemical compound C=C1C=CC=CC1=C XURVRZSODRHRNK-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000000369 oxido group Chemical group [*]=O 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
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- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 125000005545 phthalimidyl group Chemical group 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
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- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
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- 101150088264 pol gene Proteins 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- DITHIFQMPPCBCU-UHFFFAOYSA-N propa-1,2-diene Chemical group [CH]=C=C DITHIFQMPPCBCU-UHFFFAOYSA-N 0.000 description 1
- KPBSJEBFALFJTO-UHFFFAOYSA-N propane-1-sulfonyl chloride Chemical compound CCCS(Cl)(=O)=O KPBSJEBFALFJTO-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- TYRDEZUMAVRTEO-UHFFFAOYSA-N pyrimidin-5-ylmethanol Chemical compound OCC1=CN=CN=C1 TYRDEZUMAVRTEO-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
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- 229910052703 rhodium Inorganic materials 0.000 description 1
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- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 229910001023 sodium amalgam Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000008259 solid foam Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 150000008648 triflates Chemical group 0.000 description 1
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 1
- PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- RKBCYCFRFCNLTO-UHFFFAOYSA-N triisopropylamine Chemical compound CC(C)N(C(C)C)C(C)C RKBCYCFRFCNLTO-UHFFFAOYSA-N 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229960002555 zidovudine Drugs 0.000 description 1
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
Classifications
-
- 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
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C311/05—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
-
- 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
-
- 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
-
- 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
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/11—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic unsaturated carbon skeleton
-
- 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
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/12—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
- C07C311/13—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings the carbon skeleton containing six-membered aromatic rings
-
- 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
- C07C311/14—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of rings other than six-membered aromatic rings
-
- 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
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/18—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings 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
-
- 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
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Claims (62)
1. Verbindung mit der Formel
oder ein pharmazeutisch unbedenkliches Salz, Prodrug oder Ester davon, worin
R Wasserstoff, Alkoxycarbonyl-, Aralkoxycarbonyl-, Alkylcarbonyl-, Cycloalkylcarbonyl-,
Cycloalkylalkoxycarbonyl-, Cycloalkylalkanoyl-, Alkanoyl-, Aralkanoyl-, Aroyl-,
Aryloxycarbonyl-, Aryloxycarbonylalkyl-, Aryloxyalkanoyl-, Heterocyclylcarbonyl-,
Heterocyclyloxycarbonyl-, Heterocyclylalkanoyl-, Heterocyclylalkoxycarbonyl-, Heteroaralkanoyl-,
Heteroaralkoxycarbonyl-, Heteroaryloxycarbonyl-, Heteroaroyl-, Alkyl-, Alkenyl-, Alkinyl-, Cycloalkyl-,
Aryl-, Aralkyl-, Aryloxyalkyl-, Heteroaryloxyalkyl-, Hydroxyalkyl-, Aminocarbonyl-,
Aminoalkanoyl- und mono- und disubstituierte Aminocarbonyl- und mono- und disubstituierte
Aminoalkanoylreste, worin die Substituenten ausgewählt sind aus Alkyl-, Aryl-, Aralkyl-, Cycloalkyl-,
Cycloalkylalkyl-, Heteroaryl-, Heteroaralkyl-, Heterocycloalkyl-, Heterocycloalkylalkylresten
oder, wo die Aminocarbonyl- und Aminoalkanoylreste disubstituiert sind, diese Substituenten
zusammen mit dem Stickstoffatom, an das sie gebunden sind, einen Heterocycloalkyl- oder
Heteroarylrest bilden, bedeutet;
R' Wasserstoff oder Reste, wie sie für R³ definiert sind, oder R"SO&sub2;-, worin R" Reste
darstellt, wie sie für R³ definiert sind, bedeutet; oder R und R' zusammen mit dem Stickstoff,
an den sie gebunden sind, einen Heterocycloalkyl- und Heteroarylrest darstellen;
R¹ Wasserstoff, -CH&sub2;SO&sub2;NH&sub2;, -CH&sub2;CO&sub2;CH&sub3;, -CO&sub2;CH&sub3;, -CONH&sub2;, -CH&sub2;C(O)NHCH&sub3;,
-C(CH&sub3;)&sub2;(SH), -C(CH&sub3;)&sub2;(SCH&sub3;), -C(CH&sub3;)&sub2;(S[O]CH&sub3;), -C(CH&sub3;)&sub2;(S[O]&sub2;CH&sub3;), Alkyl-, Halogenalkyl-,
Alkenyl-, Alkinyl- und Cycloalkylreste und Aminosäureseitenketten ausgewählt aus Asparagin-,
S-Methylcystein- und Sulfoxid(SO)- und Sulfon(SO&sub2;)-Derivaten davon, Isoleucin-,
Alloisoleucin-, Alanin-, Leucin-, tert-Leucin-, Phenylalanin-, Ornithin-, Histidin-, Norleucin-,
Glutamin-, Threonin-, Glycin-, Allothreonin-, Serin-, O-Alkylserin-, Asparaginsäure-,
beta-Cyanoalanin- und Valinseitenketten bedeutet;
R1' und R1" unabhängig Wasserstoff und Reste, wie sie für R¹ definiert sind, bedeuten, oder
eines von R1' und R1" zusammen mit R¹ und den Kohlenstoffatomen, an die R¹, R1' und R1"
gebun
den sind, einen Cycloalkylrest darstellt;
R² Alkyl-, Aryl-, Cycloalkyl-, Cycloalkylalkyl- und Aralkylreste, welche Reste
gegebenenfalls substituiert sind mit einer Gruppe ausgewählt aus Alkyl- und Halogenresten, -NO&sub2;, -C N,
CF&sub3;, -OR&sup9;, -SR&sup9;, worin R&sup9; Wasserstoff und Alkylreste darstellt, bedeutet;
R³ Wasserstoff, Alkyl-, Halogenalkyl-, Alkenyl-, Alkinyl-, Hydroxyalkyl-, Alkoxyalkyl-,
Cycloalkyl-, Cycloalkylalkyl-, Heterocycloalkyl-, Heteroaryl-, Heterocycloalkylalkyl-, Aryl-,
Aralkyl-, Heteroaralkyl-, Aminoalkyl- und mono- und disubstituierte Aminoalkylreste, worin
die Substituenten ausgewählt sind aus Alkyl-, Aryl-, Aralkyl-, Cycloalkyl-, Cycloalkylalkyl-,
Heteroaryl-, Heteroaralkyl-, Heterocycloalkyl- und Heterocycloalkylalkylresten, oder, im
Falle eines disubstituierten Aminoalkylrestes, die Substituenten zusammen mit dem
Stickstoffatom, an das sie gebunden sind, einen Heterocycloalkyl- oder einen Heteroarylrest bilden,
bedeutet;
R&sup4; Reste darstellt, wie sie durch R³ definiert sind, mit Ausnahme von Wasserstoff;
R&sup6; Wasserstoff und Alkylreste darstellt;
x für 0, 1 oder 2 steht;
t für 0 oder 1 steht; und
Y für O, S und NR¹&sup5; steht, wobei R¹&sup5; Wasserstoff und Reste, wie sie für R³ definiert sind,
darstellt.
2. Verbindung nach Anspruch 1, worin t 0 ist, Y O ist, x 2 ist, R&sup6; = Wasserstoff und R' wie
im Anspruch 1, außer R"SO&sub2;, mit R¹ wie im Anspruch 1 definiert, außer daß O-Alkylserin durch
O-Methylserin ersetzt ist, mit R³ wie im Anspruch 1, außer Wasserstoff, mit R, R² und R&sup4; wie
im Anspruch 1 definiert.
3. Verbindung nach Anspruch 2, worin R für Aralkoxycarbonyl- und Heteroaroylreste steht.
4. Verbindung nach Anspruch 2, worin R für Carbobenzoxy-, 2-Benzofurancarbonyl- und
2-Chinolinylcarbonylreste steht.
5. Verbindung nach Anspruch 2, worin R¹ Alkyl-, Alkinyl- und Alkenylreste und
Aminosäureseitenketten ausgewählt aus der Gruppe bestehend aus Asparagin, Valin, Threonin, Allothreonin,
Isoleucin, S-Methylcystein und Sulfon- und Sulfoxidderivaten davon, Alanin und Alloisoleucin
darstellt.
6. Verbindung nach Anspruch 2, worin R¹ Methyl-, Propargyl-, t-Butyl-, Isopropyl- und
sec-Butylreste und Aminosäureseitenketten ausgewählt aus der Gruppe bestehend aus Asparagin-,
Valin-, S-Methylcystein-, Alloisoleucin-, Isoleucin-, Threonin-, Serin-, Asparaginsäure-, beta-
Cyanoalanin- und Allothreoninseitenketten darstellt.
7. Verbindung nach Anspruch 2, worin R¹ Propargyl- und t-Butylreste darstellt.
8. Verbindung nach Anspruch 2, worin R&sup4; Phenyl- und substituierte Phenylreste darstellt und
worin R³ n-Pentyl-, n-Hexyl-, n-Propyl-, i-Butyl-, Cyclohexyl-, Neopentyl-, i-Amyl- und
n-Butylreste darstellt.
9. Verbindung nach Anspruch 2, worin R³ und R&sup4; unabhängig Alkylreste mit 2 bis 5
Kohlenstoff
atomen, Cycloalkylalkylreste, Aralkylreste, Heterocycloalkylalkylreste oder
Heteroaralkylreste darstellen.
10. Verbindung nach Anspruch 2, worin R³ Isobutyl-, n-Propyl-, n-Butyl-, Isoamyl-,
Cyclohexyl-, Cyclohexylmethylreste darstellt und R&sup4; Phenyl- und substituierte Phenylreste darstellt.
11. Verbindung nach Anspruch 10, worin R³ i-Amyl oder i-Butyl ist und R&sup4; Phenyl oder
substituiertes Phenyl ausgewählt aus p-Chlorphenyl, p-Fluorphenyl, p-Nitrophenyl, p-Aminophenyl und
p-Methoxyphenyl darstellt.
12. Verbindung nach Anspruch 2, worin R&sup4; Heteroarylreste darstellt.
13. Verbindung nach Anspruch 2, worin R³ ein p-Fluorbenzylrest ist und R&sup4; ein Phenylrest
oder substituierter Phenylrest ausgewählt aus p-Chlorphenyl, p-Fluorphenyl, p-Nitrophenyl,
p-Aminophenyl und p-Methoxyphenyl ist.
14. Verbindung nach Anspruch 2, worin R³ ein 4-Pyridylmethylrest oder dessen N-Oxid ist und
R&sup4; ein Phenylrest oder ein substituierter Phenylrest ausgewählt aus p-Chlorphenyl,
p-Fluorphenyl, p-Nitrophenyl, p-Aminophenyl und p-Methoxyphenyl ist.
15. Verbindung nach Anspruch 2, worin R&sup4; einen Alkylrest mit 1 bis 6 Kohlenstoffatomen oder
einen 5- oder 6-gliedrigen Heterocyclylrest, der gegebenenfalls mit einem Alkylrest mit 1 bis
3 Kohlenstoffatomen substituiert ist, darstellt.
16. Verbindung nach Anspruch 1, worin R1' und R1" beide Wasserstoff sind und R¹ -CH&sub2;SO&sub2;NH&sub2;,
CO&sub2;NH&sub2;, CO&sub2;CH&sub3;, Alkyl- und Cycloalkylreste und Aminosäureseitenketten ausgewählt aus
Asparagin-, S-Methylcystein- und den Sulfon- und Sulfoxidderivaten davon, Histidin-,
Norleucin-, Glutamin-, Glycin-, Alloisoleucin-, Alanin-, Threonin-, Isoleucin-, Leucin-,
tert-Leucin-, Phenylalanin-, Ornithin-, Allothreonin-, Serin-, Asparaginsäure-,
beta-Cyanoalanin- und Valinseitenketten darstellt.
17. Verbindung nach Anspruch 3 oder 4, worin R¹ die Aminosäureseitenkette von Asparagin und
R einen Heteroaroylrest darstellt.
18. Verbindung nach Anspruch 2, worin R¹ einen t-Butyl- oder einen Propargylrest oder eine
Aminosäureseitenkette von Valin oder Isoleucin darstellt.
19. Verbindung nach Anspruch 18, worin R einen Arylalkanoyl-, Aryloxycarbonyl-, Alkanoyl-,
Aminocarbonyl-, monosubstituierten Aminoalkanoyl- oder disubstituierten Aminoalkanoyl- oder
Mono- oder Dialkylaminocarbonylrest darstellt.
20. Verbindung nach Anspruch 18, worin R Acetyl, N,N-Dimethylaminoacetyl,
N-Methylaminoacetyl oder N-Benzyl-N-methylaminoacetyl darstellt.
21. Verbindung nach Anspruch 1, worin R¹ einen Methylrest darstellt.
22. Verbindung nach Anspruch 21, worin R einen Alkanoyl-, Arylalkanoyl-, Aryloxyalkanoyl-
oder Arylalkyloxycarbonylrest darstellt.
23. Verbindung nach Anspruch 21, worin R einen Phenoxyacetyl-, 2-Naphthyloxyacetyl-,
Benzyloxycarbonyl- oder p-Methoxybenzyloxycarbonylrest darstellt.
24. Verbindung nach Anspruch 21, worin R einen N,N-Dialkylaminocarbonylrest darstellt.
25. Verbindung nach Anspruch 21, worin R einen Aminocarbonyl- oder einen
Alkylaminocarbonylrest darstellt.
26. Verbindung nach Anspruch 21, worin R einen N-Methylaminocarbonylrest darstellt.
27. Verbindung nach Anspruch 1, worin t = 1, R1' und R1" Wasserstoff sind, x 2 ist; Y O ist,
R&sup6; Wasserstoff ist und worin R, R², R³, R&sup4; wie im Anspruch 1 definiert sind und R¹ wie im
Anspruch 1 ist, außer O-Alkylserin, und R' wie im Anspruch 1 ist, außer R"SO&sub2;.
28. Verbindung nach Anspruch 27, worin R¹ Alkylreste mit 1 bis 4 Kohlenstoffatomen und
Alkinylreste mit 3 bis 8 Kohlenstoffatomen darstellt.
29. Verbindung nach Anspruch 27, worin R¹ Methyl-, Ethyl-, Isopropyl-, Propargyl- und
t-Butylreste darstellt.
30. Verbindung nach Anspruch 27, worin R' Wasserstoff ist und R
Gruppe,
Acetyl, Phenoxyacetyl, 2-Naphthyloxycarbonyl, Benzyloxycarbonyl oder p-Methoxybenzyloxycarbonyl
ist.
31. Verbindung nach Anspruch 27, worin R' Wasserstoff darstellt und R ein
Aralkoxycarbonylrest oder ein Heteroaralkoxycarbonylrest ist.
32. Verbindung nach Anspruch 27, worin R und R' unabhängig aus Methyl- und Phenethylresten
ausgewählt sind.
33. Verbindung nach Anspruch 27, worin R³ Alkylreste mit 2 bis 5 Kohlenstoffatomen und R&sup4;
Methyl-, Phenyl- und substituierte Phenylreste darstellt.
34. Verbindung nach Anspruch 27, worin R³ Isobutyl-, n-Propyl-, n-Butyl-, Isoamyl-,
Cyclohexylmethyl-, Cyclohexyl-, Benzyl-, p-Fluorbenzyl-, p-Methoxybenzyl-, p-Methylbenzyl- und
2-Naphthylmethylreste darstellt und R&sup4; Phenyl- und substituierte Phenylreste darstellt, worin
die Substituenten des substituierten Phenylrestes aus Chlor-, Fluor-, Nitro-, Methoxy- und
Aminosubstituenten ausgewählt sind.
35. Verbindung nach Anspruch 27, worin R³ Cyclohexylmethyl und R&sup4; Phenyl ist, oder R³ i-Amyl
und R&sup4; Phenyl ist, oder R³ i-Butyl und R&sup4; Phenyl ist, oder R³ n-Butyl und R&sup4; Phenyl ist, oder
R³ Cyclohexyl und R&sup4; Phenyl ist.
36. Verbindung nach Anspruch 27, worin R&sup4; Methyl- oder Cyclohexylreste darstellt.
37. Verbindung nach Anspruch 27, worin R und R' zusammen mit dem Stickstoff, an den sie
gebunden sind, Pyrrolidinyl-, Piperidinyl-, Morpholinyl- und Piperazinylreste darstellen.
38. Verbindung nach Anspruch 27, worin R³ Heteroaralkylreste darstellt und R&sup4; Methyl oder
Phenyl ist.
39. Verbindung nach Anspruch 1, worin t = 1, x = 2, Y für O steht, R&sup6; Wasserstoff ist und
worin R, R¹, R1", R², R&sup4; wie im Anspruch 1 definiert sind und worin R³ wie im Anspruch 1
ist, außer Wasserstoff, und R¹ wie im Anspruch 1 ist, außer O-Alkylserin, und worin R' wie im
Anspruch 1 ist, außer R"SO&sub2;.
40. Verbindung nach Anspruch 39, worin R' Wasserstoff darstellt und R Aralkoxycarbonyl- und
Heteroaroylreste darstellt.
41. Verbindung nach Anspruch 39, worin R' Wasserstoff ist und R für Carbobenzoxy-,
2-Benzofurancarbonyl- und 2-Chinolinylcarbonylreste steht.
42. Verbindung nach Anspruch 39, worin R¹, R1', und R1" unabhängig Wasserstoff und Alkylreste
mit 1 bis etwa 4 Kohlenstoffatomen, Alkenyl-, Alkinyl-, Aralkylreste und Reste ausgewählt aus
-CH&sub2;SO&sub2;NH&sub2;, -CO&sub2;CH&sub3;, -CONHCH&sub3;, -CON(CH&sub3;)&sub2;, -CH&sub2;C(O)NHCH&sub3;, -CH&sub2;C(O)N(CH&sub3;)&sub2;,
-CONH&sub2;, -C(CH&sub3;)&sub2;(SCH&sub3;), -C(CH&sub3;)&sub2;(S[O]CH&sub3;) und -C(CH&sub3;)&sub2;(S[O]CH&sub3;) darstellen.
43. Verbindung nach Anspruch 39, worin R¹, R1' und R1" unabhängig Wasserstoff, Methyl,
Ethyl, Benzyl, Phenylpropyl, Propargyl, Hydroxyl und Reste ausgewählt aus -C(O)OCH&sub3;,
-C(O)NH&sub2;, -C(O)OH darstellen.
44. Verbindung nach Anspruch 39, worin R¹ und R1' beide Wasserstoff sind und R1" C(O)NH&sub2;
ist.
45. Verbindung nach Anspruch 39, worin R¹ und R1' beide Wasserstoff sind und R1" Methyl ist.
46. Verbindung nach Anspruch 39, worin R1' Wasserstoff ist und R¹ und R1" zusammen mit den
Kohlenstoffatomen, an die sie gebunden sind, einen 3- bis 6-gliedrigen Cycloalkylrest bilden.
47. Verbindung nach Anspruch 44, worin R Carbobenzoxy-, 2-Chinolinylcarbonyl- und
2-Benzofurancarbonylreste darstellt.
48. Verbindung nach Anspruch 39, worin R³ Alkylreste mit 2 bis 5 Kohlenstoffatomen
darstellt.
49. Verbindung nach Anspruch 39, worin R³ unabhängig n-Propyl-, i-Butyl-, Cyclohexyl-,
Cyclohexylmethyl-, i-Amyl- und n-Butylreste darstellt und R&sup4; Phenyl- und substituierte Phenylreste
darstellt.
50. Verbindung nach Anspruch 39, worin R³ und R&sup4; unabhängig Alkylreste mit 2 bis 5
Kohlenstoffatomen, Cycloalkylalkylreste, Arylreste, Heteroarylreste, Aralkylreste,
Heterocycloalkylalkylreste und Heteroaralkylreste darstellen.
51. Verbindung nach Anspruch 39, worin R³ Benzyl-, p-Fluorbenzyl-, p-Methoxybenzyl-,
p-Methylbenzyl- und 2-Naphthylmethylreste darstellt und R&sup4; Phenyl- und substituierte Phenylreste
darstellt, wobei die Substituenten der substituierten Phenylreste ausgewählt sind aus Chlor-,
Fluor-, Nitro-, Methoxy- und Aminosubstituenten.
52. Verbindung nach Anspruch 2, 27 oder 39, worin R² Alkyl-, Cycloalkylalkylreste darstellt,
welche Reste gegebenenfalls substituiert sind mit Halogenresten und Resten, die dargestellt
werden durch die Formel -OR&sup9; und -SR&sup9;, worin R&sup9; Wasserstoff und Alkylreste darstellt.
53. Verbindung nach Anspruch 2, 27 oder 39, worin R² CH&sub3;SCH&sub2;CH&sub2;-, Isobutyl, n-Butyl-,
Benzyl-, 2-Naphthylmethyl- und Cyclohexylmethylreste darstellt.
54. Verbindung nach Anspruch 2, 27 oder 39, worin R³ und R&sup4; unabhängig Alkyl-,
Halogenalkyl-, Alkenyl-, Alkoxyalkyl-, Cycloalkyl-, Cycloalkylalkyl-, Heterocycloalkyl-,
Heterocycloalkylalkyl-, Heteroaryl-, Aryl-, Aralkyl- und Heteroaralkyireste darstellen.
55. Verbindung nach Anspruch 2, 27 oder 39, worin R³ Alkyl- und Alkenylreste darstellt und
R&sup4; Arylreste darstellt.
56. Pharmazeutische Zusammensetzung, umfassend eine Verbindung nach irgendeinem der
Ansprüche 1, 2, 27 oder 39 und einen pharmazeutisch unbedenklichen Träger.
57. Verwendung einer Zusammensetzung nach Anspruch 56 zur Herstellung eines Medikaments zur
Hemmung einer retroviralen Protease.
58. Verwendung nach Anspruch 57, worin die retrovirale Protease HIV-Protease ist.
59. Verwendung einer Zusammensetzung nach Anspruch 56 zur Herstellung eines Medikaments zur
Behandlung einer retroviralen Infektion.
60. Verwendung nach Anspruch 59, worin die retrovirale Infektion eine HIV-Infektion ist.
61. Verwendung einer Zusammensetzung nach Anspruch 56 zur Herstellung eines Medikaments zur
Behandlung von AIDS.
62. Verbindung nach Anspruch 1, welche ist:
Phenylmethyl[2R-hydroxy-3-[(3-methylbutyl)(methylsulfonyl)amino]-1S-(phenylmethyl)propyl]carbamat;
Phenylmethyl[2R-hydroxy-3-[(3-methylbutyl)(phenylsulfonyl)amino]-1S-(phenylmethyl)propyl]carbamat;
N1-[2R-Hydroxy-3-[(3-methylbutyl)(methylsulfonyl)amino]-1S-(phenylmethyl)propyl]-2S-[(2-chinolinylcarbonyl)amino]butandiamid;
N1-[2R-Hydroxy-3-[(3-methylbutyl)(methylsulfonyl)amino]-1S-(phenylmethyl)propyl]-2S-[(phenylmethyloxycarbonyl)amino]butandiamid;
N1-[2R-Hydroxy-3-[(3-methylbutyl)(phenylsulfonyl)amino]-1S-(phenylmethyl)propyl]-2S-[(2-chinolinylcarbonyl)amino]butandiamid;
N1-[2R-Hydroxy-3-[(3-methylbutyl)(phenylsulfonyl)amino]-1S-(phenylmethyl)propyl]-2S-[(phenylmethyloxycarbonyl)amino]butandiamid;
2S-[[(Dimethylamino)acetyl]amino]-N-[2R-hydroxy-3-[(3-methylbutyl)(phenylsulfonyl)amino]-1S-
(phenylmethyl)propyl]-3,3-dimethylbutanamid;
2S-[[(Methylamino)acetyl]amino]-N-[2R-hydroxy-3-[(3-methylbutyl)(phenylsulfonyl)amino]-1S-
(phenylmethyl)propyl]-3,3-dimethylbutanamid; oder
N1-[2R-Hydroxy-3-[(3-methylbutyl)(phenylsulfonyl)amino]-N4-methyl-1S-(phenylmethyl)propyl]-
2S-[(2-chinolinylcarbonyl)amino]butandiamid; oder
Carbaminsäure,
[3-[[2-Hydroxy-3-[(3-methylbutyl)(phenylsulfonyl)amino]-1-(phenylmethyl)propyl]amino]-2-methyl-3-oxopropyl]-, (4-Methoxyphenyl)methylester, [1S-[1R*(S*),2S*]]-.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US93498492A | 1992-08-25 | 1992-08-25 | |
PCT/US1993/007814 WO1994004492A1 (en) | 1992-08-25 | 1993-08-24 | Hydroxyethylamino sulfonamides useful as retroviral protease inhibitors |
Publications (2)
Publication Number | Publication Date |
---|---|
DE69321845D1 DE69321845D1 (en) | 1998-12-03 |
DE69321845T2 true DE69321845T2 (de) | 1999-04-29 |
Family
ID=25466397
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE69321845T Expired - Lifetime DE69321845T2 (de) | 1992-08-25 | 1993-08-24 | Hydroxyethylaminosulfonamide verwendbar als inhibitoren retroviraler proteasen |
DE69332002T Expired - Lifetime DE69332002T2 (de) | 1992-08-25 | 1993-08-24 | Hydroxyethylaminosulfonamide verwendbar als Inhibitoren retroviraler Proteasen |
DE200712000045 Active DE122007000045I2 (de) | 1992-08-25 | 1993-08-24 | Darunavir oder pharmazeutisch vertragliche Salze, Hydroxyethylaminosulfonamide verwendbar als InhibiEster oder Prodrugs davon. toren retroviraler Proteasen. |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
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DE69332002T Expired - Lifetime DE69332002T2 (de) | 1992-08-25 | 1993-08-24 | Hydroxyethylaminosulfonamide verwendbar als Inhibitoren retroviraler Proteasen |
DE200712000045 Active DE122007000045I2 (de) | 1992-08-25 | 1993-08-24 | Darunavir oder pharmazeutisch vertragliche Salze, Hydroxyethylaminosulfonamide verwendbar als InhibiEster oder Prodrugs davon. toren retroviraler Proteasen. |
Country Status (17)
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US (16) | US5843946A (de) |
EP (2) | EP0656887B1 (de) |
JP (1) | JP3657002B2 (de) |
KR (2) | KR100336699B1 (de) |
AT (2) | ATE218541T1 (de) |
AU (1) | AU680635C (de) |
CA (1) | CA2140929C (de) |
DE (3) | DE69321845T2 (de) |
DK (2) | DK0656887T3 (de) |
ES (2) | ES2177868T3 (de) |
FI (2) | FI112471B (de) |
FR (1) | FR07C0034I2 (de) |
LU (1) | LU91339I2 (de) |
NL (1) | NL300283I1 (de) |
NO (2) | NO305478B1 (de) |
PT (1) | PT810209E (de) |
WO (1) | WO1994004492A1 (de) |
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1993
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- 1993-08-24 DE DE69321845T patent/DE69321845T2/de not_active Expired - Lifetime
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