OA10054A - Compose peptidique sa preparation composition pharmaceutique le contenant et son application en medecine pour le traitement d'infections a retrovirus - Google Patents

Compose peptidique sa preparation composition pharmaceutique le contenant et son application en medecine pour le traitement d'infections a retrovirus Download PDF

Info

Publication number: OA10054A
Authority: OA; OAPI
Prior art keywords: tert; group; alkyl; compound; formula
Prior art date: 1992-03-25

Application number

OA60355A

Other languages

English (en)

French (fr)

Inventor

Colin William Greengrass

Stephen Derek Albert Street

Peter John Whittle

Original Assignee

Pfizer

Priority date (The priority date 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 date listed.)

1992-03-25

Filing date

1993-03-25

Publication date

1996-10-14

1993-03-25 Application filed by Pfizer filed Critical Pfizer

1996-10-14 Publication of OA10054A publication Critical patent/OA10054A/fr

Links

150000001875 compounds Chemical class 0.000 title claims description 98
238000002360 preparation method Methods 0.000 title claims description 53
238000011282 treatment Methods 0.000 title claims description 17
239000003814 drug Substances 0.000 title claims description 9
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
108090000765 processed proteins & peptides Proteins 0.000 title description 6
208000005074 Retroviridae Infections Diseases 0.000 title description 4
-1 R11 is H Chemical group 0.000 claims description 45
238000000034 method Methods 0.000 claims description 31
125000006239 protecting group Chemical group 0.000 claims description 19
125000000623 heterocyclic group Chemical group 0.000 claims description 18
125000003118 aryl group Chemical group 0.000 claims description 15
229950003188 isovaleryl diethylamide Drugs 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 14
229910052757 nitrogen Inorganic materials 0.000 claims description 11
229920006395 saturated elastomer Polymers 0.000 claims description 11
125000000753 cycloalkyl group Chemical group 0.000 claims description 10
125000006633 tert-butoxycarbonylamino group Chemical group 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
125000001153 fluoro group Chemical group F* 0.000 claims description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
230000008569 process Effects 0.000 claims description 6
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
229910052739 hydrogen Inorganic materials 0.000 claims description 5
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 5
230000003449 preventive effect Effects 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
206010038997 Retroviral infections Diseases 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
125000001425 triazolyl group Chemical group 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 3
239000001257 hydrogen Substances 0.000 claims description 3
125000002883 imidazolyl group Chemical group 0.000 claims description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
239000000651 prodrug Substances 0.000 claims description 3
229940002612 prodrug Drugs 0.000 claims description 3
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
125000006192 3-phenylprop-2-enyl group Chemical group [H]\C(=C(\[H])C([H])([H])*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
238000002955 isolation Methods 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 1
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims 1
125000003627 8 membered carbocyclic group Chemical group 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
125000002950 monocyclic group Chemical group 0.000 claims 1
125000003566 oxetanyl group Chemical group 0.000 claims 1
YUAQOAMSIBZOSM-LYXINOJLSA-N tert-butyl n-[(2r,3s,5s)-5-benzyl-3-hydroxy-6-[[(2s)-1-(3-imidazol-1-ylazetidin-1-yl)-3-methyl-1-oxobutan-2-yl]amino]-6-oxo-1-phenylhexan-2-yl]carbamate Chemical compound C([C@H]([C@@H](O)C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CC(C1)N1C=NC=C1)CC=1C=CC=CC=1)NC(=O)OC(C)(C)C)C1=CC=CC=C1 YUAQOAMSIBZOSM-LYXINOJLSA-N 0.000 claims 1
PCQXVCCCAGSMBW-PEBYJJCOSA-N tert-butyl n-[(2s,3s,5r)-3-hydroxy-5-[[(2s)-1-(4-imidazol-1-ylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl]carbamoyl]-1,8-diphenyloct-7-en-2-yl]carbamate Chemical compound C([C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC(CC1)N1C=NC=C1)C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OC(C)(C)C)C=CC1=CC=CC=C1 PCQXVCCCAGSMBW-PEBYJJCOSA-N 0.000 claims 1
IZWAQBCPOXQRRH-WKJCSOSYSA-N tert-butyl n-[(2s,3s,5r)-3-hydroxy-6-[[(2s,3s)-1-(4-imidazol-1-ylpiperidin-1-yl)-3-methyl-1-oxopentan-2-yl]amino]-6-oxo-1-phenyl-5-[[4-(trifluoromethoxy)phenyl]methyl]hexan-2-yl]carbamate Chemical compound C([C@@H]([C@@H](O)C[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1CCC(CC1)N1C=NC=C1)CC=1C=CC(OC(F)(F)F)=CC=1)NC(=O)OC(C)(C)C)C1=CC=CC=C1 IZWAQBCPOXQRRH-WKJCSOSYSA-N 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 91
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
239000000243 solution Substances 0.000 description 73
239000000047 product Substances 0.000 description 59
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 42
239000000203 mixture Substances 0.000 description 42
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
229910001868 water Inorganic materials 0.000 description 32
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
238000006243 chemical reaction Methods 0.000 description 28
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 24
239000002904 solvent Substances 0.000 description 24
229940073584 methylene chloride Drugs 0.000 description 22
239000011541 reaction mixture Substances 0.000 description 22
239000000741 silica gel Substances 0.000 description 22
229910002027 silica gel Inorganic materials 0.000 description 22
239000000543 intermediate Substances 0.000 description 21
239000003921 oil Substances 0.000 description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 19
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 19
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 19
235000011114 ammonium hydroxide Nutrition 0.000 description 19
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 17
239000007787 solid Substances 0.000 description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
238000004587 chromatography analysis Methods 0.000 description 14
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
238000005859 coupling reaction Methods 0.000 description 12
239000006260 foam Substances 0.000 description 12
230000008878 coupling Effects 0.000 description 11
238000010168 coupling process Methods 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
210000004027 cell Anatomy 0.000 description 10
229910052943 magnesium sulfate Inorganic materials 0.000 description 10
235000019341 magnesium sulphate Nutrition 0.000 description 10
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 10
238000000746 purification Methods 0.000 description 10
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
241000725303 Human immunodeficiency virus Species 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
239000012074 organic phase Substances 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
230000008020 evaporation Effects 0.000 description 8
208000015181 infectious disease Diseases 0.000 description 8
239000000126 substance Substances 0.000 description 8
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 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 7
125000003277 amino group Chemical group 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
238000010898 silica gel chromatography Methods 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
238000003756 stirring Methods 0.000 description 7
239000012359 Methanesulfonyl chloride Substances 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
239000002585 base Substances 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
238000011097 chromatography purification Methods 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
239000000284 extract Substances 0.000 description 6
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 5
241000700605 Viruses Species 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
239000012267 brine Substances 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
239000012230 colorless oil Substances 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
238000009472 formulation Methods 0.000 description 5
239000000843 powder Substances 0.000 description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
125000004076 pyridyl group Chemical group 0.000 description 5
239000007858 starting material Substances 0.000 description 5
239000011975 tartaric acid Substances 0.000 description 5
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
241001430294 unidentified retrovirus Species 0.000 description 5
125000000173 4-trifluoromethoxy benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC(F)(F)F)C([H])([H])* 0.000 description 4
208000030507 AIDS Diseases 0.000 description 4
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
208000031886 HIV Infections Diseases 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
229940024606 amino acid Drugs 0.000 description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 4
238000001914 filtration Methods 0.000 description 4
150000002596 lactones Chemical class 0.000 description 4
239000012071 phase Substances 0.000 description 4
125000000714 pyrimidinyl group Chemical group 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
229960004295 valine Drugs 0.000 description 4
125000004209 (C1-C8) alkyl group Chemical group 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
208000037357 HIV infectious disease Diseases 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
210000001744 T-lymphocyte Anatomy 0.000 description 3
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 3
150000001408 amides Chemical class 0.000 description 3
150000001413 amino acids Chemical class 0.000 description 3
230000000840 anti-viral effect Effects 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
238000001816 cooling Methods 0.000 description 3
239000007822 coupling agent Substances 0.000 description 3
230000018044 dehydration Effects 0.000 description 3
238000006297 dehydration reaction Methods 0.000 description 3
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 3
229940043279 diisopropylamine Drugs 0.000 description 3
201000010099 disease Diseases 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
230000000694 effects Effects 0.000 description 3
208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 3
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
229910000041 hydrogen chloride Inorganic materials 0.000 description 3
125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
102000004196 processed proteins & peptides Human genes 0.000 description 3
230000000750 progressive effect Effects 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
230000009467 reduction Effects 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
239000000725 suspension Substances 0.000 description 3
235000002906 tartaric acid Nutrition 0.000 description 3
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 3
238000012360 testing method Methods 0.000 description 3
125000001544 thienyl group Chemical group 0.000 description 3
230000009466 transformation Effects 0.000 description 3
239000004474 valine Substances 0.000 description 3
NNQBAGFIYBBAFL-UHFFFAOYSA-N 1-(diethoxymethyl)imidazole Chemical compound CCOC(OCC)N1C=CN=C1 NNQBAGFIYBBAFL-UHFFFAOYSA-N 0.000 description 2
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 2
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
239000005695 Ammonium acetate Substances 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
108091005804 Peptidases Proteins 0.000 description 2
239000004365 Protease Substances 0.000 description 2
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
125000003342 alkenyl group Chemical group 0.000 description 2
229940043376 ammonium acetate Drugs 0.000 description 2
235000019257 ammonium acetate Nutrition 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
239000003443 antiviral agent Substances 0.000 description 2
238000003556 assay Methods 0.000 description 2
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
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150000002894 organic compounds Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
QMLWSAXEQSBAAQ-UHFFFAOYSA-N oxetan-3-ol Chemical compound OC1COC1 QMLWSAXEQSBAAQ-UHFFFAOYSA-N 0.000 description 1
150000002924 oxiranes Chemical group 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000007170 pathology Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
230000035515 penetration Effects 0.000 description 1
229960001639 penicillamine Drugs 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
229960003424 phenylacetic acid Drugs 0.000 description 1
239000003279 phenylacetic acid Substances 0.000 description 1
NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
XIMLAVRHZBUYBE-UHFFFAOYSA-N piperidin-2-one;hydrate;hydrochloride Chemical compound O.Cl.O=C1CCCCN1 XIMLAVRHZBUYBE-UHFFFAOYSA-N 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
108010043277 recombinant soluble CD4 Proteins 0.000 description 1
230000010076 replication Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
238000007142 ring opening reaction Methods 0.000 description 1
239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
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 1
238000000926 separation method Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000011343 solid material Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
230000017960 syncytium formation Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
PTXURQZIMCLTNW-ZDUSSCGKSA-N tert-butyl n-[(2s)-1-(3-imidazol-1-ylazetidin-1-yl)-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound C1N(C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)C)CC1N1C=NC=C1 PTXURQZIMCLTNW-ZDUSSCGKSA-N 0.000 description 1
YXZISSQOFIZLNX-JTQLQIEISA-N tert-butyl n-[(2s)-1-oxo-1-phenylpropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](C)C(=O)C1=CC=CC=C1 YXZISSQOFIZLNX-JTQLQIEISA-N 0.000 description 1
YOHNPWQCDUNXJA-UWVYSXLVSA-N tert-butyl n-[(2s,3r,5s)-5-[(4-chlorophenyl)methyl]-3-hydroxy-6-[[(2s)-1-(3-imidazol-1-ylazetidin-1-yl)-3-methyl-1-oxobutan-2-yl]amino]-6-oxo-1-phenylhexan-2-yl]carbamate Chemical compound C([C@@H]([C@H](O)C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CC(C1)N1C=NC=C1)CC=1C=CC(Cl)=CC=1)NC(=O)OC(C)(C)C)C1=CC=CC=C1 YOHNPWQCDUNXJA-UWVYSXLVSA-N 0.000 description 1
DDLFESZLXFANDD-UAMZLAIYSA-N tert-butyl n-[(2s,3s,5r)-3-hydroxy-6-[[(2s)-1-(4-imidazol-1-ylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl]amino]-6-oxo-1-phenyl-5-[[4-(trifluoromethoxy)phenyl]methyl]hexan-2-yl]carbamate Chemical compound C([C@@H]([C@@H](O)C[C@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC(CC1)N1C=NC=C1)CC=1C=CC(OC(F)(F)F)=CC=1)NC(=O)OC(C)(C)C)C1=CC=CC=C1 DDLFESZLXFANDD-UAMZLAIYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000010998 test method Methods 0.000 description 1
125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
231100000167 toxic agent Toxicity 0.000 description 1
239000003440 toxic substance Substances 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
238000000844 transformation Methods 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
230000029812 viral genome replication Effects 0.000 description 1
230000003612 virological effect Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Peptides Or Proteins (AREA)
Plural Heterocyclic Compounds (AREA)

OA60355A 1992-03-25 1993-03-25 Compose peptidique sa preparation composition pharmaceutique le contenant et son application en medecine pour le traitement d'infections a retrovirus OA10054A (fr)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB929206462A GB9206462D0 (en)	1992-03-25	1992-03-25	Antiviral peptides

Publications (1)

Publication Number	Publication Date
OA10054A true OA10054A (fr)	1996-10-14

Family

ID=10712788

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA60355A OA10054A (fr)	1992-03-25	1993-03-25	Compose peptidique sa preparation composition pharmaceutique le contenant et son application en medecine pour le traitement d'infections a retrovirus

Country Status (11)

Country	Link
CN (1)	CN1077716A (is)
GB (1)	GB9206462D0 (is)
HR (1)	HRP930283A2 (is)
IL (1)	IL105099A0 (is)
IS (1)	IS3988A (is)
MA (1)	MA22838A1 (is)
MX (1)	MX9301694A (is)
MY (1)	MY131321A (is)
OA (1)	OA10054A (is)
UY (1)	UY23555A1 (is)
ZA (1)	ZA932079B (is)

1992
- 1992-03-25 GB GB929206462A patent/GB9206462D0/en active Pending
1993
- 1993-03-09 HR HR9206462.5A patent/HRP930283A2/hr not_active Application Discontinuation
- 1993-03-18 IL IL105099A patent/IL105099A0/xx unknown
- 1993-03-19 MY MYPI93000495A patent/MY131321A/en unknown
- 1993-03-22 IS IS3988A patent/IS3988A/is unknown
- 1993-03-23 CN CN93103206A patent/CN1077716A/zh active Pending
- 1993-03-23 MA MA23132A patent/MA22838A1/fr unknown
- 1993-03-24 UY UY23555A patent/UY23555A1/es unknown
- 1993-03-24 ZA ZA932079A patent/ZA932079B/xx unknown
- 1993-03-25 MX MX9301694A patent/MX9301694A/es unknown
- 1993-03-25 OA OA60355A patent/OA10054A/fr unknown

Also Published As

Publication number	Publication date
UY23555A1 (es)	1993-09-08
ZA932079B (en)	1994-09-26
MA22838A1 (fr)	1993-10-01
CN1077716A (zh)	1993-10-27
IS3988A (is)	1993-09-26
IL105099A0 (en)	1993-07-08
HRP930283A2 (en)	1997-08-31
GB9206462D0 (en)	1992-05-06
MY131321A (en)	2007-08-30
MX9301694A (es)	1993-09-01

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