HRP930283A2 - Antiviral peptides - Google Patents

Antiviral peptides Download PDF

Info

Publication number: HRP930283A2
Authority: HR; Croatia
Prior art keywords: alkyl; compound; cycloalkyl; hydroxy; formula
Prior art date: 1992-03-25

Application number

HR9206462.5A

Other languages

English (en)

Croatian (hr)

Inventor

Colin William Greengras

Peter John Whitle

Stephen Derek Albert Street

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

1993-03-09

Publication date

1997-08-31

1993-03-09 Application filed by Pfizer filed Critical Pfizer

1997-08-31 Publication of HRP930283A2 publication Critical patent/HRP930283A2/hr

Links

108090000765 processed proteins & peptides Proteins 0.000 title description 5
230000000840 anti-viral effect Effects 0.000 title description 4
102000004196 processed proteins & peptides Human genes 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 92
238000002360 preparation method Methods 0.000 claims description 55
238000000034 method Methods 0.000 claims description 53
238000006243 chemical reaction Methods 0.000 claims description 40
-1 chloro, iodo Chemical group 0.000 claims description 37
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 31
125000000623 heterocyclic group Chemical group 0.000 claims description 27
125000003118 aryl group Chemical group 0.000 claims description 26
125000006239 protecting group Chemical group 0.000 claims description 21
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 19
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 19
230000008569 process Effects 0.000 claims description 16
229920006395 saturated elastomer Polymers 0.000 claims description 15
238000011282 treatment Methods 0.000 claims description 15
150000003839 salts Chemical class 0.000 claims description 14
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims description 14
229950003188 isovaleryl diethylamide Drugs 0.000 claims description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 13
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
125000001153 fluoro group Chemical group F* 0.000 claims description 9
229910052757 nitrogen Inorganic materials 0.000 claims description 9
229910052739 hydrogen Inorganic materials 0.000 claims description 8
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 7
229910052799 carbon Inorganic materials 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
125000001424 substituent group Chemical group 0.000 claims description 7
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 7
206010038997 Retroviral infections Diseases 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 6
229910052731 fluorine Inorganic materials 0.000 claims description 6
239000011737 fluorine Substances 0.000 claims description 6
238000011321 prophylaxis Methods 0.000 claims description 6
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 5
230000015572 biosynthetic process Effects 0.000 claims description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
125000001425 triazolyl group Chemical group 0.000 claims description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
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 3
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 3
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
239000003960 organic solvent Substances 0.000 claims description 3
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 description 3
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 description 3
239000003085 diluting agent Substances 0.000 claims description 2
239000004615 ingredient Substances 0.000 claims description 2
238000002955 isolation Methods 0.000 claims description 2
VHLOQUQGTBOALD-YTQWTBANSA-N tert-butyl n-[(2r,3s,5s)-5-benzyl-3-hydroxy-6-[[(2s)-1-(4-imidazol-1-ylpiperidin-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)N1CCC(CC1)N1C=NC=C1)CC=1C=CC=CC=1)NC(=O)OC(C)(C)C)C1=CC=CC=C1 VHLOQUQGTBOALD-YTQWTBANSA-N 0.000 claims description 2
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 claims description 2
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 description 2
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 claims description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
125000003566 oxetanyl group Chemical group 0.000 claims 2
125000004008 6 membered carbocyclic group Chemical group 0.000 claims 1
125000003627 8 membered carbocyclic group Chemical group 0.000 claims 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 98
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 75
239000000243 solution Substances 0.000 description 64
239000000047 product Substances 0.000 description 56
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 48
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 44
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 25
238000004587 chromatography analysis Methods 0.000 description 25
239000000203 mixture Substances 0.000 description 25
239000000741 silica gel Substances 0.000 description 25
229910002027 silica gel Inorganic materials 0.000 description 25
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 24
229910052943 magnesium sulfate Inorganic materials 0.000 description 24
235000019341 magnesium sulphate Nutrition 0.000 description 24
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
239000002904 solvent Substances 0.000 description 24
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
239000000543 intermediate Substances 0.000 description 22
239000003921 oil Substances 0.000 description 20
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 19
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
239000007787 solid Substances 0.000 description 18
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
238000000746 purification Methods 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-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
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 12
230000008878 coupling Effects 0.000 description 11
238000010168 coupling process Methods 0.000 description 11
241000725303 Human immunodeficiency virus Species 0.000 description 10
208000015181 infectious disease Diseases 0.000 description 10
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
210000004027 cell Anatomy 0.000 description 9
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
238000003756 stirring Methods 0.000 description 9
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
125000003277 amino group Chemical group 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
230000008020 evaporation Effects 0.000 description 8
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 7
239000012044 organic layer Substances 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
239000007858 starting material Substances 0.000 description 7
241001430294 unidentified retrovirus Species 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
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
229960000583 acetic acid Drugs 0.000 description 5
229940024606 amino acid Drugs 0.000 description 5
239000002585 base Substances 0.000 description 5
239000012267 brine Substances 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
238000001914 filtration Methods 0.000 description 5
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
229910000041 hydrogen chloride Inorganic materials 0.000 description 5
239000000843 powder Substances 0.000 description 5
125000004076 pyridyl group Chemical group 0.000 description 5
238000010898 silica gel chromatography Methods 0.000 description 5
208000030507 AIDS Diseases 0.000 description 4
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
239000012230 colorless oil Substances 0.000 description 4
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 4
239000011521 glass Substances 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
125000000714 pyrimidinyl group Chemical group 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
238000010992 reflux Methods 0.000 description 4
238000012360 testing method Methods 0.000 description 4
125000001544 thienyl group Chemical group 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
XAVCNOSDJOIMOB-UHFFFAOYSA-N (2,5-dioxopyrrolidin-3-yl) oxetan-2-yl carbonate Chemical compound C1C(=O)NC(=O)C1OC(=O)OC1CCO1 XAVCNOSDJOIMOB-UHFFFAOYSA-N 0.000 description 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
208000031886 HIV Infections 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
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
210000001744 T-lymphocyte Anatomy 0.000 description 3
241000700605 Viruses Species 0.000 description 3
150000001413 amino acids Chemical class 0.000 description 3
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
238000001816 cooling Methods 0.000 description 3
239000007822 coupling agent Substances 0.000 description 3
238000010511 deprotection reaction Methods 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
238000001035 drying Methods 0.000 description 3
230000000694 effects Effects 0.000 description 3
125000005843 halogen group Chemical group 0.000 description 3
150000001261 hydroxy acids Chemical class 0.000 description 3
150000002596 lactones Chemical class 0.000 description 3
239000010410 layer Substances 0.000 description 3
125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 description 3
238000010647 peptide synthesis reaction Methods 0.000 description 3
239000012071 phase Substances 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
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
238000000926 separation method Methods 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
238000010561 standard procedure Methods 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
239000011975 tartaric acid Substances 0.000 description 3
229940095064 tartrate Drugs 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
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
229960004295 valine Drugs 0.000 description 3
UEVGWVOLUCPPDE-NXCFDTQHSA-N (2S,4S,5R)-2-benzyl-4-[tert-butyl(dimethyl)silyl]oxy-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-phenylhexanoic acid Chemical compound C([C@@H](NC(=O)OC(C)(C)C)[C@H](C[C@H](CC=1C=CC=CC=1)C(O)=O)O[Si](C)(C)C(C)(C)C)C1=CC=CC=C1 UEVGWVOLUCPPDE-NXCFDTQHSA-N 0.000 description 2
JAHKKPSKFZUAHI-UHFFFAOYSA-N 1-(1-isocyano-3-methylbut-1-enyl)sulfonyl-4-methylbenzene Chemical compound CC(C)C=C([N+]#[C-])S(=O)(=O)C1=CC=C(C)C=C1 JAHKKPSKFZUAHI-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
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
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HSPKIXPRSRGOQK-UHFFFAOYSA-N isoquinolin-5-ylmethanol Chemical compound N1=CC=C2C(CO)=CC=CC2=C1 HSPKIXPRSRGOQK-UHFFFAOYSA-N 0.000 description 1
VLONTUPZTAEOIH-UHFFFAOYSA-N isoquinolin-7-ylmethanol Chemical compound C1=CN=CC2=CC(CO)=CC=C21 VLONTUPZTAEOIH-UHFFFAOYSA-N 0.000 description 1
ILRSABOCKMOFGW-UHFFFAOYSA-N isoquinoline-5-carbaldehyde Chemical compound N1=CC=C2C(C=O)=CC=CC2=C1 ILRSABOCKMOFGW-UHFFFAOYSA-N 0.000 description 1
QEAGQILEKLFCEK-UHFFFAOYSA-N isoquinoline-7-carbaldehyde Chemical compound C1=CN=CC2=CC(C=O)=CC=C21 QEAGQILEKLFCEK-UHFFFAOYSA-N 0.000 description 1
150000003893 lactate salts Chemical class 0.000 description 1
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
238000000465 moulding Methods 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
229910000069 nitrogen hydride Inorganic materials 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000002894 organic compounds Chemical class 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
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 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
229960001639 penicillamine Drugs 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical class [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
125000003386 piperidinyl group Chemical group 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
238000003825 pressing Methods 0.000 description 1
230000001737 promoting 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
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
WTTIBCHOELPGFK-LBPRGKRZSA-N r82150 Chemical class C1N(CC=C(C)C)[C@@H](C)CN2C(=S)NC3=CC=CC1=C32 WTTIBCHOELPGFK-LBPRGKRZSA-N 0.000 description 1
108010043277 recombinant soluble CD4 Proteins 0.000 description 1
230000010076 replication Effects 0.000 description 1
230000003362 replicative effect Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
230000001177 retroviral effect 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
239000012266 salt solution 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
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
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
125000004434 sulfur atom Chemical group 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
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
HQMYWQCBINPHBB-MRVPVSSYSA-N tert-butyl (2r)-2-methyl-4-oxopiperidine-1-carboxylate Chemical compound C[C@@H]1CC(=O)CCN1C(=O)OC(C)(C)C HQMYWQCBINPHBB-MRVPVSSYSA-N 0.000 description 1
MMVDGCVHNGWMJO-DGEZQFQFSA-N tert-butyl N-[(2R,3S,5S)-5-benzyl-3-hydroxy-6-[[(2S)-3-methyl-1-oxo-1-[4-(1,2,4-triazol-4-yl)piperidin-1-yl]butan-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)N1CCC(CC1)N1C=NN=C1)CC=1C=CC=CC=1)NC(=O)OC(C)(C)C)C1=CC=CC=C1 MMVDGCVHNGWMJO-DGEZQFQFSA-N 0.000 description 1
ZJTYRNPLVNMVPQ-LBPRGKRZSA-N tert-butyl n-[(2s)-1-oxo-3-phenylpropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](C=O)CC1=CC=CC=C1 ZJTYRNPLVNMVPQ-LBPRGKRZSA-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
238000002560 therapeutic procedure Methods 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
230000009466 transformation Effects 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
150000003852 triazoles Chemical class 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
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
230000029812 viral genome replication Effects 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1
230000003313 weakening 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)
Peptides Or Proteins (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

HR9206462.5A 1992-03-25 1993-03-09 Antiviral peptides HRP930283A2 (en)

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
HRP930283A2 true HRP930283A2 (en)	1997-08-31

Family

ID=10712788

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR9206462.5A HRP930283A2 (en)	1992-03-25	1993-03-09	Antiviral peptides

Country Status (11)

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

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
MY131321A (en)	2007-08-30
MA22838A1 (fr)	1993-10-01
IS3988A (is)	1993-09-26
GB9206462D0 (en)	1992-05-06
OA10054A (fr)	1996-10-14
IL105099A0 (en)	1993-07-08
CN1077716A (zh)	1993-10-27
ZA932079B (en)	1994-09-26
MX9301694A (es)	1993-09-01

Legal Events

Date	Code	Title
1997-08-31	A1OB	Publication of a patent application
1997-12-31	AIPI	Request for the grant of a patent on the basis of a substantive examination of a patent application
1998-03-24	OBST	Application withdrawn

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