IE54927B1 - Oligopeptide prodrugs - Google Patents
Oligopeptide prodrugsInfo
- Publication number
- IE54927B1 IE54927B1 IE1144/83A IE114483A IE54927B1 IE 54927 B1 IE54927 B1 IE 54927B1 IE 1144/83 A IE1144/83 A IE 1144/83A IE 114483 A IE114483 A IE 114483A IE 54927 B1 IE54927 B1 IE 54927B1
- Authority
- IE
- Ireland
- Prior art keywords
- compound
- alanyl
- glycine
- mixture
- residue
- Prior art date
Links
- 229940002612 prodrug Drugs 0.000 title claims abstract description 31
- 239000000651 prodrug Substances 0.000 title claims abstract description 31
- 108010038807 Oligopeptides Proteins 0.000 title claims abstract description 29
- 102000015636 Oligopeptides Human genes 0.000 title claims abstract description 29
- 239000000203 mixture Substances 0.000 claims description 83
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 73
- 150000001875 compounds Chemical class 0.000 claims description 64
- -1 aminobutyl Chemical group 0.000 claims description 49
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 49
- 150000001413 amino acids Chemical class 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 24
- 238000006073 displacement reaction Methods 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000006239 protecting group Chemical group 0.000 claims description 13
- 239000004471 Glycine Substances 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical group SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims description 11
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 10
- 150000003839 salts Chemical class 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
- 230000000845 anti-microbial effect Effects 0.000 claims description 8
- 239000004599 antimicrobial Substances 0.000 claims description 7
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 4
- 230000000507 anthelmentic effect Effects 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000003412 L-alanyl group Chemical group [H]N([H])[C@@](C([H])([H])[H])(C(=O)[*])[H] 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 210000000170 cell membrane Anatomy 0.000 abstract description 14
- 239000000126 substance Substances 0.000 abstract description 13
- 230000000269 nucleophilic effect Effects 0.000 abstract description 5
- 230000000973 chemotherapeutic effect Effects 0.000 abstract description 4
- 230000035699 permeability Effects 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 64
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 55
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 239000007787 solid Substances 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 229940024606 amino acid Drugs 0.000 description 16
- 235000001014 amino acid Nutrition 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 102000004196 processed proteins & peptides Human genes 0.000 description 12
- 108010016626 Dipeptides Proteins 0.000 description 11
- 102000035195 Peptidases Human genes 0.000 description 11
- 108091005804 Peptidases Proteins 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 239000002253 acid Substances 0.000 description 10
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 238000004809 thin layer chromatography Methods 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 229920001184 polypeptide Polymers 0.000 description 7
- 235000019833 protease Nutrition 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 229960002949 fluorouracil Drugs 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 239000002246 antineoplastic agent Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 241000222122 Candida albicans Species 0.000 description 4
- 108090000301 Membrane transport proteins Proteins 0.000 description 4
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 229960002669 albendazole Drugs 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000003096 antiparasitic agent Substances 0.000 description 4
- 229940125687 antiparasitic agent Drugs 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 239000000852 hydrogen donor Substances 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 235000019419 proteases Nutrition 0.000 description 4
- 230000000087 stabilizing effect Effects 0.000 description 4
- 239000003039 volatile agent Substances 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
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- RAOCRURYZCVHMG-UHFFFAOYSA-N N-(6-propoxy-1H-benzimidazol-2-yl)carbamic acid methyl ester Chemical compound CCCOC1=CC=C2N=C(NC(=O)OC)NC2=C1 RAOCRURYZCVHMG-UHFFFAOYSA-N 0.000 description 3
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- 125000001980 alanyl group Chemical group 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
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- 238000001727 in vivo Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 3
- 229950003188 isovaleryl diethylamide Drugs 0.000 description 3
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- AHLPHDHHMVZTML-BYPYZUCNSA-N ornithyl group Chemical group N[C@@H](CCCN)C(=O)O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 3
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- OBETXYAYXDNJHR-SSDOTTSWSA-M (2r)-2-ethylhexanoate Chemical compound CCCC[C@@H](CC)C([O-])=O OBETXYAYXDNJHR-SSDOTTSWSA-M 0.000 description 2
- PQXMQZYDBQBWNL-UHFFFAOYSA-N 1,3-benzothiazol-2-ylmethanol Chemical compound C1=CC=C2SC(CO)=NC2=C1 PQXMQZYDBQBWNL-UHFFFAOYSA-N 0.000 description 2
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- 238000000354 decomposition reaction Methods 0.000 description 2
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- 238000009792 diffusion process Methods 0.000 description 2
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- 125000001288 lysyl group Chemical group 0.000 description 2
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- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
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- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
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- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 229960004454 oxfendazole Drugs 0.000 description 1
- BEZZFPOZAYTVHN-UHFFFAOYSA-N oxfendazole Chemical compound C=1C=C2NC(NC(=O)OC)=NC2=CC=1S(=O)C1=CC=CC=C1 BEZZFPOZAYTVHN-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-VENIDDJXSA-N palladium-100 Chemical compound [100Pd] KDLHZDBZIXYQEI-VENIDDJXSA-N 0.000 description 1
- 229950007337 parbendazole Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 108010082406 peptide permease Proteins 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- XNQULTQRGBXLIA-UHFFFAOYSA-O phosphonic anhydride Chemical compound O[P+](O)=O XNQULTQRGBXLIA-UHFFFAOYSA-O 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- CAEWJEXPFKNBQL-UHFFFAOYSA-N prop-2-enyl carbonochloridate Chemical compound ClC(=O)OCC=C CAEWJEXPFKNBQL-UHFFFAOYSA-N 0.000 description 1
- QZWHWHNCPFEXLL-UHFFFAOYSA-N propan-2-yl n-[2-(1,3-thiazol-4-yl)-3h-benzimidazol-5-yl]carbamate Chemical compound N1C2=CC(NC(=O)OC(C)C)=CC=C2N=C1C1=CSC=N1 QZWHWHNCPFEXLL-UHFFFAOYSA-N 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000010583 slow cooling Methods 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940073490 sodium glutamate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 239000004308 thiabendazole Substances 0.000 description 1
- 229960004546 thiabendazole Drugs 0.000 description 1
- WJCNZQLZVWNLKY-UHFFFAOYSA-N thiabendazole Chemical compound S1C=NC(C=2NC3=CC=CC=C3N=2)=C1 WJCNZQLZVWNLKY-UHFFFAOYSA-N 0.000 description 1
- 235000010296 thiabendazole Nutrition 0.000 description 1
- 229960002898 threonine Drugs 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 1
- 229960001082 trimethoprim Drugs 0.000 description 1
- 239000001974 tryptic soy broth Substances 0.000 description 1
- 108010050327 trypticase-soy broth Proteins 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37953782A | 1982-05-18 | 1982-05-18 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE831144L IE831144L (en) | 1983-11-18 |
| IE54927B1 true IE54927B1 (en) | 1990-03-28 |
Family
ID=23497666
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE1144/83A IE54927B1 (en) | 1982-05-18 | 1983-05-17 | Oligopeptide prodrugs |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0094815B1 (enExample) |
| JP (1) | JPS58219151A (enExample) |
| AT (1) | ATE39930T1 (enExample) |
| AU (2) | AU563196B2 (enExample) |
| CA (1) | CA1247088A (enExample) |
| DE (1) | DE3378914D1 (enExample) |
| DK (1) | DK207583A (enExample) |
| ES (1) | ES522476A0 (enExample) |
| GR (1) | GR81343B (enExample) |
| IE (1) | IE54927B1 (enExample) |
| PT (1) | PT76677B (enExample) |
| ZA (1) | ZA832844B (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4479898A (en) * | 1982-05-18 | 1984-10-30 | Smithkline Beckman Corporation | Oligopeptide prodrugs |
| US5126451A (en) * | 1988-02-11 | 1992-06-30 | Warner-Lambert Company | Renin inhibitors containing α-heteroatom amino acids |
| US5036054A (en) * | 1988-02-11 | 1991-07-30 | Warner-Lambert Company | Renin inhibitors containing alpha-heteroatom amino acids |
| JP2578044B2 (ja) * | 1992-03-14 | 1997-02-05 | 呉羽化学工業株式会社 | フェニルアラニン−グリシン誘導体、その製造方法、及びその誘導体を含有する抗腫瘍剤 |
| FR2736055B1 (fr) * | 1995-06-29 | 1997-09-12 | Laphal Sa Lab | Nouveaux thiophenoxy peptides, leur procede de preparation et les compositions pharmaceutiques en renfermant |
| IT1292438B1 (it) * | 1997-06-30 | 1999-02-08 | Zambon Spa | Derivati peptidomimetici inibitori suicidi della proliferazione del hiv |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH338197A (fr) * | 1954-08-18 | 1959-05-15 | Uclaf Societe Anonyme | Procédé d'obtention de peptides |
| CH616912A5 (en) * | 1974-06-17 | 1980-04-30 | Sandoz Ag | Process for the preparation of dipeptide derivatives. |
| PH14064A (en) * | 1977-05-06 | 1981-01-26 | Pfizer | Phenylgycine derivatives,pharmaceutical compositions and method of use |
| FR2434392A1 (fr) * | 1978-04-28 | 1980-03-21 | Toyo Jozo Kk | Nouveau compose disulfure utile dans la chromatographie de covalence |
| US4258193A (en) * | 1978-07-13 | 1981-03-24 | Toyo Jozo Kabushiki Kaisha | Disulfide derivatives having S--S exchange reactivity |
| IL58849A (en) * | 1978-12-11 | 1983-03-31 | Merck & Co Inc | Carboxyalkyl dipeptides and derivatives thereof,their preparation and pharmaceutical compositions containing them |
| US4284624A (en) * | 1980-05-02 | 1981-08-18 | E. R. Squibb & Sons, Inc. | Mixed disulfides |
| EP0046742B1 (en) * | 1980-08-25 | 1984-06-27 | KabiVitrum AB | Peptide substrates for determination of protease activity |
| JPS5754151A (en) * | 1980-09-18 | 1982-03-31 | Takeda Chem Ind Ltd | Physiologically active substance b-52653 and its preparation |
| CY1406A (en) * | 1980-12-18 | 1988-04-22 | Schering Corp | Substituted dipeptides, processes for their preparation and pharmaceutical compositions containing them and their use in the inhibition of enkephalinase |
| JPS57123155A (en) * | 1981-01-26 | 1982-07-31 | Takeda Chem Ind Ltd | Preparation of pyrrolidine derivative and its intermediate |
| DE3127930A1 (de) * | 1981-07-15 | 1983-01-27 | A. Nattermann & Cie GmbH, 5000 Köln | Neue optisch aktive dipeptide, verfahren zur herstellung und diese enthaltende pharmazeutische praeparate |
| DE3173632D1 (en) * | 1981-09-11 | 1986-03-13 | Amersham Int Plc | Derivatives of iodothyronine compounds and their use in an assay for the free iodothyronine compounds |
| JPS58105948A (ja) * | 1981-12-16 | 1983-06-24 | Fujirebio Inc | ジペプチド誘導体 |
| US4427582A (en) * | 1982-06-08 | 1984-01-24 | Smithkline Beckman Corporation | Antimicrobial disulfide prodrugs |
-
1983
- 1983-04-22 ZA ZA832844A patent/ZA832844B/xx unknown
- 1983-04-22 AU AU13883/83A patent/AU563196B2/en not_active Ceased
- 1983-04-27 CA CA000426790A patent/CA1247088A/en not_active Expired
- 1983-05-10 DK DK207583A patent/DK207583A/da not_active Application Discontinuation
- 1983-05-11 PT PT76677A patent/PT76677B/pt unknown
- 1983-05-16 EP EP83302736A patent/EP0094815B1/en not_active Expired
- 1983-05-16 DE DE8383302736T patent/DE3378914D1/de not_active Expired
- 1983-05-16 AT AT83302736T patent/ATE39930T1/de not_active IP Right Cessation
- 1983-05-17 ES ES522476A patent/ES522476A0/es active Granted
- 1983-05-17 GR GR71370A patent/GR81343B/el unknown
- 1983-05-17 IE IE1144/83A patent/IE54927B1/en unknown
- 1983-05-18 JP JP58088334A patent/JPS58219151A/ja active Pending
-
1987
- 1987-04-16 AU AU71759/87A patent/AU586743B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP0094815A2 (en) | 1983-11-23 |
| CA1247088A (en) | 1988-12-20 |
| IE831144L (en) | 1983-11-18 |
| PT76677B (en) | 1986-01-14 |
| EP0094815B1 (en) | 1989-01-11 |
| AU563196B2 (en) | 1987-07-02 |
| ES8407010A1 (es) | 1984-08-16 |
| DE3378914D1 (en) | 1989-02-16 |
| EP0094815A3 (en) | 1986-03-12 |
| AU586743B2 (en) | 1989-07-20 |
| PT76677A (en) | 1983-06-01 |
| AU7175987A (en) | 1987-08-13 |
| DK207583D0 (da) | 1983-05-10 |
| DK207583A (da) | 1983-11-19 |
| ZA832844B (en) | 1984-03-28 |
| AU1388383A (en) | 1983-11-24 |
| GR81343B (enExample) | 1984-12-11 |
| JPS58219151A (ja) | 1983-12-20 |
| ATE39930T1 (de) | 1989-01-15 |
| ES522476A0 (es) | 1984-08-16 |
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