USH1649H - HIV protease inhibitor combinations - Google Patents
HIV protease inhibitor combinations Download PDFInfo
- Publication number
- USH1649H USH1649H US08/436,868 US43686895A USH1649H US H1649 H USH1649 H US H1649H US 43686895 A US43686895 A US 43686895A US H1649 H USH1649 H US H1649H
- Authority
- US
- United States
- Prior art keywords
- pharmaceutically acceptable
- formula
- compound
- acceptable derivative
- hiv
- 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.)
- Abandoned
Links
- 239000004030 hiv protease inhibitor Substances 0.000 title description 4
- 229940122440 HIV protease inhibitor Drugs 0.000 title 1
- 241000725303 Human immunodeficiency virus Species 0.000 claims abstract description 28
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims abstract description 26
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 201000010099 disease Diseases 0.000 claims abstract description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 52
- 239000000203 mixture Substances 0.000 claims description 28
- 230000002401 inhibitory effect Effects 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 12
- 229940126544 HIV-1 protease inhibitor Drugs 0.000 claims description 11
- 239000003085 diluting agent Substances 0.000 claims description 6
- 230000000840 anti-viral effect Effects 0.000 claims description 4
- 239000003112 inhibitor Substances 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 108091005804 Peptidases Proteins 0.000 claims description 2
- 239000004365 Protease Substances 0.000 claims description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims 8
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 abstract description 18
- 108010016183 Human immunodeficiency virus 1 p16 protease Proteins 0.000 abstract description 15
- 206010034133 Pathogen resistance Diseases 0.000 abstract description 3
- 230000003612 virological effect Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 35
- 239000000243 solution Substances 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
- 125000000217 alkyl group Chemical group 0.000 description 20
- 239000007787 solid Substances 0.000 description 19
- 235000019439 ethyl acetate Nutrition 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- OQHZMGOXOOOFEE-SYQUUIDJSA-N tert-butyl n-[(2s,3r)-3-hydroxy-4-[[(2r,3s)-2-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-[4-(2-morpholin-4-yl-2-oxoethoxy)phenyl]butyl]amino]-1-phenylbutan-2-yl]carbamate Chemical compound C([C@H](NC(=O)OC(C)(C)C)[C@H](O)CNC[C@@H](O)[C@H](CC=1C=CC(OCC(=O)N2CCOCC2)=CC=1)NC(=O)OC(C)(C)C)C1=CC=CC=C1 OQHZMGOXOOOFEE-SYQUUIDJSA-N 0.000 description 13
- 150000003839 salts Chemical class 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 239000001257 hydrogen Substances 0.000 description 9
- 229910052739 hydrogen Inorganic materials 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 230000037396 body weight Effects 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 208000030507 AIDS Diseases 0.000 description 7
- 125000003342 alkenyl group Chemical group 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- QPVWMQXBTCSLCB-BYAJYZPISA-N (2s)-n-[(2s,3s,4r,5s)-3,4-dihydroxy-5-[[(2s)-3-methyl-2-[[methyl(pyridin-2-ylmethyl)carbamoyl]amino]butanoyl]amino]-1,6-diphenylhexan-2-yl]-3-methyl-2-[[methyl(pyridin-2-ylmethyl)carbamoyl]amino]butanamide Chemical compound N([C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)[C@H](O)[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)N(C)CC=1N=CC=CC=1)C(C)C)C(=O)N(C)CC1=CC=CC=N1 QPVWMQXBTCSLCB-BYAJYZPISA-N 0.000 description 6
- SSIBMWPFXYSVEK-CUPIEXAXSA-N A 80987 Chemical compound N([C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)[C@@H](O)C[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=NC=CC=1)C(=O)OCC1=CC=CC=N1 SSIBMWPFXYSVEK-CUPIEXAXSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 208000031886 HIV Infections Diseases 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- -1 1,1-dimethylethoxy Chemical group 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 125000000623 heterocyclic group Chemical group 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 239000002777 nucleoside Substances 0.000 description 5
- 150000003833 nucleoside derivatives Chemical class 0.000 description 5
- 229960000311 ritonavir Drugs 0.000 description 5
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 5
- 239000012453 solvate Substances 0.000 description 5
- 208000037357 HIV infectious disease Diseases 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000003443 antiviral agent Substances 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 4
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 229910004809 Na2 SO4 Inorganic materials 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 229940125773 compound 10 Drugs 0.000 description 3
- 229940126214 compound 3 Drugs 0.000 description 3
- 229940125898 compound 5 Drugs 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 229940093915 gynecological organic acid Drugs 0.000 description 3
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 3
- 239000006210 lotion Substances 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 229960002555 zidovudine Drugs 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
- 206010001513 AIDS related complex Diseases 0.000 description 2
- 241000220479 Acacia Species 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 108010010369 HIV Protease Proteins 0.000 description 2
- 101900297506 Human immunodeficiency virus type 1 group M subtype B Reverse transcriptase/ribonuclease H Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- VZUNGTLZRAYYDE-UHFFFAOYSA-N N-methyl-N'-nitro-N-nitrosoguanidine Chemical compound O=NN(C)C(=N)N[N+]([O-])=O VZUNGTLZRAYYDE-UHFFFAOYSA-N 0.000 description 2
- 229910017917 NH4 Cl Inorganic materials 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960004106 citric acid Drugs 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 229960002656 didanosine Drugs 0.000 description 2
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 229960000443 hydrochloric acid Drugs 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 125000000468 ketone group Chemical group 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 229940098895 maleic acid Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229960004838 phosphoric acid Drugs 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 229960001367 tartaric acid Drugs 0.000 description 2
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 229960000523 zalcitabine Drugs 0.000 description 2
- XJSQNGVSDAUVJJ-AWEZNQCLSA-N (2S)-2-amino-N'-methyl-2-propan-2-yl-N'-[(2-propan-2-yl-1,3-thiazol-4-yl)methyl]propanediamide Chemical compound CC(C)C1=NC(CN(C)C(=O)[C@](N)(C(C)C)C(N)=O)=CS1 XJSQNGVSDAUVJJ-AWEZNQCLSA-N 0.000 description 1
- ZYJPUMXJBDHSIF-NSHDSACASA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZYJPUMXJBDHSIF-NSHDSACASA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 1
- ZXNDTHXXZRQCTC-UHFFFAOYSA-N 2-[4-[tert-butylcarbamoyl(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinoline-2-carbonylamino)butanediamide Chemical compound C=1C=C2C=CC=CC2=NC=1C(=O)NC(CC(N)=O)(C(N)=O)C(C(O)CN(CC(C)C)C(=O)NC(C)(C)C)CC1=CC=CC=C1 ZXNDTHXXZRQCTC-UHFFFAOYSA-N 0.000 description 1
- LLLQAMNGYJQUKK-UHFFFAOYSA-N 2-bromo-1-morpholin-4-ylethanone Chemical compound BrCC(=O)N1CCOCC1 LLLQAMNGYJQUKK-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- 125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
- 125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 208000032484 Accidental exposure to product Diseases 0.000 description 1
- 101100177155 Arabidopsis thaliana HAC1 gene Proteins 0.000 description 1
- 108010017640 Aspartic Acid Proteases Proteins 0.000 description 1
- 102000004580 Aspartic Acid Proteases Human genes 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 206010069803 Injury associated with device Diseases 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 101100434170 Oryza sativa subsp. japonica ACR2.1 gene Proteins 0.000 description 1
- 101100434171 Oryza sativa subsp. japonica ACR2.2 gene Proteins 0.000 description 1
- 101150108015 STR6 gene Proteins 0.000 description 1
- 101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 150000008043 acidic salts Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- PKSROMPNLONTJT-UHFFFAOYSA-N azanium;chloroform;methanol;hydroxide Chemical compound N.O.OC.ClC(Cl)Cl PKSROMPNLONTJT-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N carbon tetrachloride Substances ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- ONCCWDRMOZMNSM-FBCQKBJTSA-N compound Z Chemical compound N1=C2C(=O)NC(N)=NC2=NC=C1C(=O)[C@H]1OP(O)(=O)OC[C@H]1O ONCCWDRMOZMNSM-FBCQKBJTSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000012153 long-term therapy Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- GRWIABMEEKERFV-UHFFFAOYSA-N methanol;oxolane Chemical compound OC.C1CCOC1 GRWIABMEEKERFV-UHFFFAOYSA-N 0.000 description 1
- DGEYTDCFMQMLTH-UHFFFAOYSA-N methanol;propan-2-ol Chemical compound OC.CC(C)O DGEYTDCFMQMLTH-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- CZFNISFYDPIDNM-UHFFFAOYSA-N n,n-dimethylformamide;oxolane Chemical compound CN(C)C=O.C1CCOC1 CZFNISFYDPIDNM-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229940074355 nitric acid Drugs 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 229940064914 retrovir Drugs 0.000 description 1
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
- 229960001852 saquinavir Drugs 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 101150035983 str1 gene Proteins 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229940032330 sulfuric acid Drugs 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003239 susceptibility assay Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
-
- 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
- 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
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0205—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/021—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)n-C(=0)-, n being 5 or 6; for n > 6, classification in C07K5/06 - C07K5/10, according to the moiety having normal peptide bonds
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/436,868 USH1649H (en) | 1987-07-31 | 1995-05-17 | HIV protease inhibitor combinations |
| CA002153270A CA2153270A1 (en) | 1994-07-05 | 1995-07-05 | Hiv protease inhibitor combinations |
| EP95304718A EP0691345A3 (de) | 1994-07-05 | 1995-07-05 | Kombinationen von HIV-Protease Inhibitoren |
| JP7169630A JPH08109131A (ja) | 1994-07-05 | 1995-07-05 | Ｈｉｖプロテアーゼ抑制因子組成物 |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US7997887A | 1987-07-31 | 1987-07-31 | |
| US27061494A | 1994-07-05 | 1994-07-05 | |
| US08/436,868 USH1649H (en) | 1987-07-31 | 1995-05-17 | HIV protease inhibitor combinations |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US27061494A Continuation-In-Part | 1987-07-31 | 1994-07-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| USH1649H true USH1649H (en) | 1997-05-06 |
Family
ID=26954391
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US08/436,868 Abandoned USH1649H (en) | 1987-07-31 | 1995-05-17 | HIV protease inhibitor combinations |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | USH1649H (de) |
| EP (1) | EP0691345A3 (de) |
| JP (1) | JPH08109131A (de) |
| CA (1) | CA2153270A1 (de) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6100277A (en) * | 1994-06-03 | 2000-08-08 | G.D. Searle & Co. | Retroviral protease inhibitor combinations |
| US6538006B1 (en) | 1998-07-08 | 2003-03-25 | Pharmacia Corporation | Retroviral protease inhibitors |
| US20060240410A1 (en) * | 1994-06-03 | 2006-10-26 | G.D. Searle & Co. | Retroviral protease inhibitor combinations |
| WO2007094983A2 (en) * | 2006-02-03 | 2007-08-23 | Tanox, Inc. | Methods and compositions for the inhibition of hiv infection of t cells |
| USRE42889E1 (en) | 1992-08-25 | 2011-11-01 | G.D. Searle Llc | α- and β- amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors |
| USRE43596E1 (en) | 1992-08-25 | 2012-08-21 | G.D. Searle Llc | α- and β-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6037157A (en) * | 1995-06-29 | 2000-03-14 | Abbott Laboratories | Method for improving pharmacokinetics |
| AU723563B2 (en) * | 1996-01-26 | 2000-08-31 | Pharmacia & Upjohn Company | Use of a combination of delavirdine and one or more protease inhibitors in HIV-1 infected patients |
| US6180634B1 (en) | 1997-11-13 | 2001-01-30 | Merck & Co., Inc. | Combination therapy for the treatment of AIDS |
| EP1151992B1 (de) * | 1999-01-21 | 2003-09-17 | Kaneka Corporation | Methode zur reinigung und abtrennung von (2s,3s)- oder (2r,3s)-halohydrinderivaten |
| CA2417127A1 (en) * | 2000-07-24 | 2002-01-31 | The University Of Queensland | Compounds and inhibitors of phospholipases |
| EP1346979A4 (de) * | 2000-11-30 | 2005-11-09 | Ajinomoto Kk | Verfahren zur herstellung von n-geschützten aminoalkoholen und n-geschützten aminoepoxiden |
| AU2003227446A1 (en) * | 2002-04-26 | 2003-11-10 | Ajinomoto Co., Inc. | Process for producing aminoepoxide |
| DE102010004957A1 (de) | 2010-01-14 | 2011-07-21 | Universitätsklinikum Jena, 07743 | Biologisch wirksame Moleküle zur Beeinflussung von Virus-, Bakterien-, Parasiten-infizierten Zellen und/oder Tumorzellen und Verfahren zu deren Anwendung |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0580402A2 (de) * | 1992-07-20 | 1994-01-26 | E.R. Squibb & Sons, Inc. | Amindiole als Protease-Hemmer |
| US5484926A (en) * | 1993-10-07 | 1996-01-16 | Agouron Pharmaceuticals, Inc. | HIV protease inhibitors |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5142056A (en) | 1989-05-23 | 1992-08-25 | Abbott Laboratories | Retroviral protease inhibiting compounds |
| FR2490872A1 (fr) | 1980-09-19 | 1982-03-26 | Thomson Csf | Ligne a retard a cavites couplees pour tube a ondes progressives et tube a ondes progressives comportant une telle ligne |
| GB8927913D0 (en) | 1989-12-11 | 1990-02-14 | Hoffmann La Roche | Amino acid derivatives |
| WO1992008701A1 (en) | 1990-11-19 | 1992-05-29 | Monsanto Company | Retroviral protease inhibitors |
| IE913840A1 (en) | 1990-11-20 | 1992-05-20 | Abbott Lab | Retroviral protease inhibiting compounds |
| US5110979A (en) | 1991-01-15 | 1992-05-05 | Imperial Chemical Industries Plc | Trisubstituted benzoic acid intermediates |
| EP0541168B1 (de) | 1991-11-08 | 1998-03-11 | Merck & Co. Inc. | HIV-Protease-Inhibitoren verwendbar in der AIDS-Behandlung |
| WO1994002149A1 (en) | 1992-07-17 | 1994-02-03 | The General Hospital Corporation | Convergent combination anti-viral therapy |
| MX9308016A (es) | 1992-12-22 | 1994-08-31 | Lilly Co Eli | Compuestos inhibidores de la proteasa del virus de la inmunodeficiencia humana, procedimiento para su preparacion y formulacion farmaceutica que los contiene. |
| JP4369973B2 (ja) | 2007-12-27 | 2009-11-25 | 株式会社日本製鋼所 | カッタ装置 |
-
1995
- 1995-05-17 US US08/436,868 patent/USH1649H/en not_active Abandoned
- 1995-07-05 EP EP95304718A patent/EP0691345A3/de not_active Withdrawn
- 1995-07-05 CA CA002153270A patent/CA2153270A1/en not_active Abandoned
- 1995-07-05 JP JP7169630A patent/JPH08109131A/ja active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0580402A2 (de) * | 1992-07-20 | 1994-01-26 | E.R. Squibb & Sons, Inc. | Amindiole als Protease-Hemmer |
| US5484926A (en) * | 1993-10-07 | 1996-01-16 | Agouron Pharmaceuticals, Inc. | HIV protease inhibitors |
Non-Patent Citations (4)
| Title |
|---|
| D. pillay et al., "HIV-1 Protease Inhibitors: . . . Clin. Potential", Rev. Med. Virol., vol. 5, pp. 23-33. |
| D. pillay et al., HIV 1 Protease Inhibitors: . . . Clin. Potential , Rev. Med. Virol., vol. 5, pp. 23 33. * |
| HIV 1 Protease Inhibitors: Their Development, Mechanism of Action and Clinical Potential, D. Pillay et al, Rev. Med. Virol. , 5: 23 33, 1995. * |
| HIV-1 Protease Inhibitors: Their Development, Mechanism of Action and Clinical Potential, D. Pillay et al, Rev. Med. Virol., 5: 23-33, 1995. |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE42889E1 (en) | 1992-08-25 | 2011-11-01 | G.D. Searle Llc | α- and β- amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors |
| USRE43596E1 (en) | 1992-08-25 | 2012-08-21 | G.D. Searle Llc | α- and β-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors |
| USRE43802E1 (en) | 1992-08-25 | 2012-11-13 | G.D. Searle Llc | α- and β-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors |
| US6100277A (en) * | 1994-06-03 | 2000-08-08 | G.D. Searle & Co. | Retroviral protease inhibitor combinations |
| US20060240410A1 (en) * | 1994-06-03 | 2006-10-26 | G.D. Searle & Co. | Retroviral protease inhibitor combinations |
| US6538006B1 (en) | 1998-07-08 | 2003-03-25 | Pharmacia Corporation | Retroviral protease inhibitors |
| US7026333B1 (en) | 1998-07-08 | 2006-04-11 | G. D. Searle & Co. | Retroviral protease inhibitors |
| WO2007094983A2 (en) * | 2006-02-03 | 2007-08-23 | Tanox, Inc. | Methods and compositions for the inhibition of hiv infection of t cells |
| WO2007094983A3 (en) * | 2006-02-03 | 2007-12-06 | Tanox Inc | Methods and compositions for the inhibition of hiv infection of t cells |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH08109131A (ja) | 1996-04-30 |
| CA2153270A1 (en) | 1996-01-06 |
| EP0691345A3 (de) | 1996-02-28 |
| EP0691345A2 (de) | 1996-01-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1302468B1 (de) | Verfahren und Intermediate zur Herstellung von retroviralen Proteasehemmern | |
| USH1649H (en) | HIV protease inhibitor combinations | |
| KR100520737B1 (ko) | 아스파틸 프로테아제 억제제의 전구약물로서 술폰아미드유도체 | |
| US6037157A (en) | Method for improving pharmacokinetics | |
| DE69534549T2 (de) | Kombination von retroviralen Proteasehemmern | |
| EP0735019B1 (de) | Inhibitoren retroviraler Proteasen | |
| CZ176298A3 (cs) | Sloučeniny inhibující proteázy retrovirů | |
| RO115726B1 (ro) | Derivati substituiti ai pentanamidei, procedeu de obtinere, intermediari in sinteza acestora, compozitie care ii contine, si metode de tratament | |
| PL187747B1 (pl) | Zastosowanie sulfonamidowego inhibitora proteazy HIV | |
| WO1992017176A1 (en) | Retroviral protease inhibiting compounds | |
| CA3095164A1 (en) | Calpain modulators and therapeutic uses thereof | |
| JP2012528160A (ja) | Ｈｉｖプロテアーゼ阻害薬 | |
| US6673821B2 (en) | Nitrogen heterocycle inhibitors of aspartyl protease | |
| JP2019534332A (ja) | Ｈｉｖ／ａｉｄｓに対する強力な三環式ｐ２リガンド含有ｈｉｖプロテアーゼ阻害剤 | |
| US20130274254A1 (en) | Inhibitors of cytochrome p450 (cyp3a4) | |
| KR20010032055A (ko) | Ａｉｄｓ 치료를 위한 혼합물 치료방법 | |
| JP2000502997A (ja) | レトロウイルスプロテアーゼ抑制化合物 | |
| EP3778577B1 (de) | Neuartige verbindung mit enteropeptasehemmender wirkung | |
| TWI292752B (en) | Retroviral protease inhibiting compounds | |
| JP2004043324A (ja) | 芳香族アミン化合物及びその用途 | |
| MXPA00006315A (en) | Sulphonamide derivatives as prodrugs of aspartyl protease inhibitors | |
| MXPA00011244A (en) | Retroviral protease inhibiting compounds | |
| MXPA00006316A (es) | Profarmacos de inhibidores de aspartil proteasa | |
| JP2003504383A (ja) | アルファ−ヒドロキシ−ガンマ−［［（炭素環式−又はヘテロ環式−置換）アミノ］カルボニル］アルカンアミド誘導体及びこれらの使用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AS | Assignment |
Owner name: BRISTOL-MYERS SQUIBB COMPANY, NEW JERSEY Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BARRISH, JOEL C.;COLONNO, RICHARD J.;LIN, PIN-FANG M.;REEL/FRAME:007665/0003;SIGNING DATES FROM 19950510 TO 19950515 |
|
| STCF | Information on status: patent grant |
Free format text: PATENTED CASE |