NO784354L - Peptidderivater og fremstilling derav - Google Patents

Peptidderivater og fremstilling derav

Info

Publication number: NO784354L
Authority: NO; Norway
Prior art keywords: benzyloxycarbonyl; ethylphosphonic acid; alanyl; amino; acid
Prior art date: 1977-12-23

Application number

NO784354A

Other languages

English (en)

Norwegian (no)

Inventor

Frank Ratcliffe Atherton

Michael John Hall

Cedric Herbert Hassall

Robert Wilson Lambert

Peter Stuart Ringrose

Original Assignee

Hoffmann La Roche

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.)

1977-12-23

Filing date

1978-12-22

Publication date

1979-06-26

1978-12-22 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1979-06-26 Publication of NO784354L publication Critical patent/NO784354L/no

Links

238000004519 manufacturing process Methods 0.000 title claims description 32
108090000765 processed proteins & peptides Proteins 0.000 title description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 102
238000000034 method Methods 0.000 claims description 61
150000001875 compounds Chemical class 0.000 claims description 34
125000006239 protecting group Chemical group 0.000 claims description 27
125000000217 alkyl group Chemical group 0.000 claims description 21
150000003839 salts Chemical class 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 14
239000001257 hydrogen Substances 0.000 claims description 13
125000004432 carbon atom Chemical group C* 0.000 claims description 11
235000018102 proteins Nutrition 0.000 claims description 11
108090000623 proteins and genes Proteins 0.000 claims description 11
102000004169 proteins and genes Human genes 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
125000003277 amino group Chemical group 0.000 claims description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 5
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
239000000825 pharmaceutical preparation Substances 0.000 claims description 4
235000008206 alpha-amino acids Nutrition 0.000 claims description 3
125000000524 functional group Chemical group 0.000 claims description 3
150000002431 hydrogen Chemical class 0.000 claims description 3
238000002360 preparation method Methods 0.000 claims description 3
150000001371 alpha-amino acids Chemical class 0.000 claims description 2
125000004953 trihalomethyl group Chemical group 0.000 claims description 2
239000003242 anti bacterial agent Substances 0.000 claims 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 163
238000002844 melting Methods 0.000 description 157
230000008018 melting Effects 0.000 description 157
238000000354 decomposition reaction Methods 0.000 description 145
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 135
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 123
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 117
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 90
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 84
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 80
239000000203 mixture Substances 0.000 description 80
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 56
239000000243 solution Substances 0.000 description 56
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 48
239000003921 oil Substances 0.000 description 45
235000019198 oils Nutrition 0.000 description 45
239000007787 solid Substances 0.000 description 45
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
238000001953 recrystallisation Methods 0.000 description 36
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
229960000583 acetic acid Drugs 0.000 description 31
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
239000000706 filtrate Substances 0.000 description 27
239000007858 starting material Substances 0.000 description 26
239000000047 product Substances 0.000 description 25
238000001704 evaporation Methods 0.000 description 24
230000008020 evaporation Effects 0.000 description 24
-1 2-methylthio-ethyl Chemical group 0.000 description 21
PNRXIXZOPVPLMM-UHFFFAOYSA-N 1-hydroxypyrrolidine-2,5-dione;2-[methyl(phenylmethoxycarbonyl)amino]acetic acid Chemical compound ON1C(=O)CCC1=O.OC(=O)CN(C)C(=O)OCC1=CC=CC=C1 PNRXIXZOPVPLMM-UHFFFAOYSA-N 0.000 description 19
239000012043 crude product Substances 0.000 description 19
239000003054 catalyst Substances 0.000 description 16
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 14
239000002253 acid Substances 0.000 description 14
239000011550 stock solution Substances 0.000 description 14
238000009833 condensation Methods 0.000 description 13
230000005494 condensation Effects 0.000 description 13
230000002378 acidificating effect Effects 0.000 description 12
239000010410 layer Substances 0.000 description 11
DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 10
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 10
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 10
239000002244 precipitate Substances 0.000 description 10
239000012362 glacial acetic acid Substances 0.000 description 9
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 9
238000000746 purification Methods 0.000 description 8
GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical class C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 7
229940024606 amino acid Drugs 0.000 description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
GATNOFPXSDHULC-UHFFFAOYSA-N ethylphosphonic acid Chemical compound CCP(O)(O)=O GATNOFPXSDHULC-UHFFFAOYSA-N 0.000 description 7
229910000042 hydrogen bromide Inorganic materials 0.000 description 7
239000002904 solvent Substances 0.000 description 7
239000000126 substance Substances 0.000 description 7
238000001665 trituration Methods 0.000 description 7
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
239000007859 condensation product Substances 0.000 description 6
238000001914 filtration Methods 0.000 description 6
239000000463 material Substances 0.000 description 6
GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 6
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
238000003756 stirring Methods 0.000 description 6
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
239000006286 aqueous extract Substances 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
239000003729 cation exchange resin Substances 0.000 description 5
238000003776 cleavage reaction Methods 0.000 description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 5
230000007017 scission Effects 0.000 description 5
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 4
150000008064 anhydrides Chemical class 0.000 description 4
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 4
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 4
239000002024 ethyl acetate extract Substances 0.000 description 4
239000000284 extract Substances 0.000 description 4
239000003208 petroleum Substances 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
UIQSKEDQPSEGAU-UWTATZPHSA-N (R)-(1-aminoethyl)phosphonic acid Chemical compound C[C@H](N)P(O)(O)=O UIQSKEDQPSEGAU-UWTATZPHSA-N 0.000 description 3
CBWFTZNMONHKNZ-UHFFFAOYSA-N 2-[methyl(phenylmethoxycarbonyl)amino]acetic acid Chemical compound OC(=O)CN(C)C(=O)OCC1=CC=CC=C1 CBWFTZNMONHKNZ-UHFFFAOYSA-N 0.000 description 3
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
239000004471 Glycine Substances 0.000 description 3
CJUMAFVKTCBCJK-UHFFFAOYSA-N N-benzyloxycarbonylglycine Chemical compound OC(=O)CNC(=O)OCC1=CC=CC=C1 CJUMAFVKTCBCJK-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
RBZNWFFBUNHRQC-KHSUWTBESA-N [(3S)-3-amino-1-[[(2S)-2-aminopentanoyl]amino]-2-oxohexyl]phosphonic acid Chemical compound N[C@@H](CCC)C(=O)C(NC([C@@H](N)CCC)=O)P(O)(O)=O RBZNWFFBUNHRQC-KHSUWTBESA-N 0.000 description 3
125000005099 aryl alkyl carbonyl group Chemical group 0.000 description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
239000012876 carrier material Substances 0.000 description 3
238000010828 elution Methods 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
238000000605 extraction Methods 0.000 description 3
229960002449 glycine Drugs 0.000 description 3
238000011065 in-situ storage Methods 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
238000005342 ion exchange Methods 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 3
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
MFAOBGXYLNLLJE-HNNXBMFYSA-N (2,5-dioxopyrrolidin-1-yl) (2s)-3-methyl-2-(phenylmethoxycarbonylamino)butanoate Chemical compound N([C@@H](C(C)C)C(=O)ON1C(CCC1=O)=O)C(=O)OCC1=CC=CC=C1 MFAOBGXYLNLLJE-HNNXBMFYSA-N 0.000 description 2
NSJDRLWFFAWSFP-NSHDSACASA-N (2s)-2-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound CCC[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 NSJDRLWFFAWSFP-NSHDSACASA-N 0.000 description 2
CANZBRDGRHNSGZ-NSHDSACASA-N (2s)-3-methyl-2-(phenylmethoxycarbonylamino)butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 CANZBRDGRHNSGZ-NSHDSACASA-N 0.000 description 2
NNEHOKZDWLJKHP-LBPRGKRZSA-N (2s)-3-methyl-2-[methyl(phenylmethoxycarbonyl)amino]butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)N(C)C(=O)OCC1=CC=CC=C1 NNEHOKZDWLJKHP-LBPRGKRZSA-N 0.000 description 2
LACZBXBXDSGMGS-UHFFFAOYSA-N 2-(cyclopropylamino)acetic acid;hydrochloride Chemical compound Cl.OC(=O)CNC1CC1 LACZBXBXDSGMGS-UHFFFAOYSA-N 0.000 description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
AIHWEWRRKFVMEH-UHFFFAOYSA-N 2-[benzyl(phenylmethoxycarbonyl)amino]acetic acid Chemical compound C=1C=CC=CC=1COC(=O)N(CC(=O)O)CC1=CC=CC=C1 AIHWEWRRKFVMEH-UHFFFAOYSA-N 0.000 description 2
YGKNIMGNXSLCFF-UHFFFAOYSA-N 2-[cyclopropyl(phenylmethoxycarbonyl)amino]acetic acid Chemical compound C=1C=CC=CC=1COC(=O)N(CC(=O)O)C1CC1 YGKNIMGNXSLCFF-UHFFFAOYSA-N 0.000 description 2
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
241000194032 Enterococcus faecalis Species 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
GWSVFEHNNMXSGW-VDTYLAMSSA-N [(1r)-1-[[(2s)-2-amino-3-(1h-imidazol-5-yl)propanoyl]amino]ethyl]phosphonic acid Chemical compound OP(=O)(O)[C@H](C)NC(=O)[C@@H](N)CC1=CNC=N1 GWSVFEHNNMXSGW-VDTYLAMSSA-N 0.000 description 2
JBXBOVLKPXAIDD-RITPCOANSA-N [(1r)-1-[[(2s)-2-aminopentanoyl]amino]ethyl]phosphonic acid Chemical compound CCC[C@H](N)C(=O)N[C@@H](C)P(O)(O)=O JBXBOVLKPXAIDD-RITPCOANSA-N 0.000 description 2
AVUUDZKTDWRXEG-NBFOIZRFSA-N [(3S)-3-amino-2-oxo-1-(2-phenylpropan-2-yloxycarbonylamino)hexyl]phosphonic acid Chemical compound CCC[C@@H](C(=O)C(NC(=O)OC(C)(C)C1=CC=CC=C1)P(=O)(O)O)N AVUUDZKTDWRXEG-NBFOIZRFSA-N 0.000 description 2
LQCQFDGRRKXTOP-XBGLIEATSA-N [(5S)-5-amino-3-[[(2S)-2-aminopropanoyl]amino]-1-(methylamino)-2,4-dioxohexan-3-yl]phosphonic acid Chemical compound N(C)CC(=O)C(NC([C@@H](N)C)=O)(C([C@@H](N)C)=O)P(O)(O)=O LQCQFDGRRKXTOP-XBGLIEATSA-N 0.000 description 2
MSEBNAXFIZIHJN-YFKPBYRVSA-N [[(2s)-2-aminopentanoyl]amino]methylphosphonic acid Chemical compound CCC[C@H](N)C(=O)NCP(O)(O)=O MSEBNAXFIZIHJN-YFKPBYRVSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
BHAYDBSYOBONRV-IUYQGCFVSA-N alafosfalin Chemical compound C[C@H](N)C(=O)N[C@@H](C)P(O)(O)=O BHAYDBSYOBONRV-IUYQGCFVSA-N 0.000 description 2
125000003342 alkenyl group Chemical group 0.000 description 2
MMCPOSDMTGQNKG-UHFFFAOYSA-N anilinium chloride Chemical compound Cl.NC1=CC=CC=C1 MMCPOSDMTGQNKG-UHFFFAOYSA-N 0.000 description 2
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
239000000872 buffer Substances 0.000 description 2
125000004744 butyloxycarbonyl group Chemical group 0.000 description 2
239000006227 byproduct Substances 0.000 description 2
150000001718 carbodiimides Chemical class 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
238000001816 cooling Methods 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
125000000753 cycloalkyl group Chemical group 0.000 description 2
238000010908 decantation Methods 0.000 description 2
LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
VOZPZBSGYPGXEE-UHFFFAOYSA-N ethyl 2-(cyclopropylamino)acetate Chemical compound CCOC(=O)CNC1CC1 VOZPZBSGYPGXEE-UHFFFAOYSA-N 0.000 description 2
229960002885 histidine Drugs 0.000 description 2
238000007327 hydrogenolysis reaction Methods 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical group OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 2
125000005544 phthalimido group Chemical group 0.000 description 2
FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
239000000725 suspension Substances 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
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 2
238000005406 washing Methods 0.000 description 2
238000010626 work up procedure Methods 0.000 description 2
OLMBOHVAVKHHTK-UHFFFAOYSA-N (1-carboxy-2,2-dimethylpropyl)azanium;chloride Chemical compound Cl.CC(C)(C)C(N)C(O)=O OLMBOHVAVKHHTK-UHFFFAOYSA-N 0.000 description 1
QGEQKVZQPWSOTI-VIFPVBQESA-N (2s)-2-[methyl(phenylmethoxycarbonyl)amino]propanoic acid Chemical compound OC(=O)[C@H](C)N(C)C(=O)OCC1=CC=CC=C1 QGEQKVZQPWSOTI-VIFPVBQESA-N 0.000 description 1
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Classifications

- 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
- C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
- 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
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S930/00—Peptide or protein sequence
- Y10S930/01—Peptide or protein sequence
- Y10S930/27—Cyclic peptide or cyclic protein

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Chemical & Material Sciences (AREA)
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Molecular Biology (AREA)
Biochemistry (AREA)
Medicinal Chemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Veterinary Medicine (AREA)
Oncology (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
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Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Communicable Diseases (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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NO784354A 1977-12-23 1978-12-22 Peptidderivater og fremstilling derav NO784354L (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB5366877		1977-12-23
GB7845272		1978-11-20

Publications (1)

Publication Number	Publication Date
NO784354L true NO784354L (no)	1979-06-26

Family

ID=26267312

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO784354A NO784354L (no)	1977-12-23	1978-12-22	Peptidderivater og fremstilling derav

Country Status (24)

Country	Link
US (1)	US4250085A (cs)
EP (1)	EP0002822B1 (cs)
JP (1)	JPS5492922A (cs)
AR (1)	AR222479A1 (cs)
AT (1)	AT365166B (cs)
AU (1)	AU4258178A (cs)
BR (1)	BR7808474A (cs)
CA (1)	CA1108125A (cs)
CS (1)	CS210680B2 (cs)
DE (2)	DE2855786A1 (cs)
DK (1)	DK581178A (cs)
ES (2)	ES476264A1 (cs)
FI (1)	FI783959A7 (cs)
FR (3)	FR2453866A1 (cs)
GR (1)	GR72974B (cs)
IL (1)	IL56241A0 (cs)
IT (1)	IT1102755B (cs)
LU (1)	LU80715A1 (cs)
MC (1)	MC1243A1 (cs)
NL (1)	NL7812314A (cs)
NO (1)	NO784354L (cs)
NZ (1)	NZ189205A (cs)
PT (1)	PT68978A (cs)
SE (1)	SE7813274L (cs)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0026867A1 (de) *	1979-09-28	1981-04-15	F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft	Peptidylphosphonsäuren, deren Herstellung und Verwendung und sie enthaltende pharmazeutische Präparate
JPS5885897A (ja) *	1981-11-17	1983-05-23	Kyowa Hakko Kogyo Co Ltd	光学活性な１−アミノ−２−（４−ヒドロキシフエニル）エチルホスホン酸およびその誘導体
JPS5831992A (ja) *	1981-08-19	1983-02-24	Kyowa Hakko Kogyo Co Ltd	新規生理活性物質ｋ−４およびその製造法
EP0061172B1 (en) *	1981-03-20	1985-06-19	Kyowa Hakko Kogyo Co., Ltd.	Phosphorus-containing oligopeptides, processes for preparation thereof and a pharmaceutical composition containing the same
JPS57156498A (en) *	1981-03-20	1982-09-27	Kyowa Hakko Kogyo Co Ltd	Novel physiologically active substance k-26
DE3368418D1 (en) *	1982-09-17	1987-01-29	Kyowa Hakko Kogyo Kk	Phosphorus-containing peptide derivative
PT77368A (en) *	1982-09-27	1983-10-01	Lilly Co Eli	Improved process for preparing immunomodulating agents or rela-ting there to
US4482488A (en) *	1982-09-27	1984-11-13	Eli Lilly And Company	Antibiotic A53868 and process for production thereof
FR2584077B1 (fr) *	1985-06-28	1988-07-08	Irceba	L-di ou tripeptides possedant une activite biologique utilisable en medecine humaine et veterinaire, procede pour leur obtention et medicament en contenant
HUT52785A (en) *	1988-03-03	1990-08-28	Squibb & Sons Inc	Process for producing 1,2-hydroxy-phosphonates and derivatives
AU3964489A (en) *	1988-07-08	1990-02-05	Smithkline Beckman Corporation	Retroviral protease binding peptides
WO1990009172A1 (en) *	1989-02-16	1990-08-23	Pfizer Inc.	Phosphorus containing renin inhibitors
US5468732A (en) *	1989-02-16	1995-11-21	Pfizer Inc.	Phosphorus containing renin inhibitors
DE4417478A1 (de)	1994-05-19	1995-11-23	Basf Ag	Verfahren zur Herstellung N-Z-geschützter N-methylierter Aminosäuren
US11174288B2 (en)	2016-12-06	2021-11-16	Northeastern University	Heparin-binding cationic peptide self-assembling peptide amphiphiles useful against drug-resistant bacteria

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL48835A (en) *	1975-01-27	1979-05-31	Sparamedica Ag	Amino acyl and peptidyl derivatives of phophonic acids, their preparation and pharmaceutical compositions containingthem
CA1057082A (en) *	1976-05-13	1979-06-26	Dale K. Bell	Air piston differential lockout
JPS6037745Y2 (ja) *	1976-05-18	1985-11-11	富士写真フイルム株式会社	磁気テ−プカセツト
IT1081511B (it) *	1976-07-13	1985-05-21	Hoffmann La Roche	Derivati di peptidi e loro preparazione

1978
- 1978-12-08 CA CA317,617A patent/CA1108125A/en not_active Expired
- 1978-12-15 AU AU42581/78A patent/AU4258178A/en active Pending
- 1978-12-18 NZ NZ189205A patent/NZ189205A/xx unknown
- 1978-12-18 IL IL56241A patent/IL56241A0/xx unknown
- 1978-12-19 NL NL7812314A patent/NL7812314A/xx not_active Application Discontinuation
- 1978-12-19 FR FR7835650A patent/FR2453866A1/fr not_active Withdrawn
- 1978-12-20 US US05/971,156 patent/US4250085A/en not_active Expired - Lifetime
- 1978-12-20 MC MC781350A patent/MC1243A1/fr unknown
- 1978-12-21 AT AT0918478A patent/AT365166B/de not_active IP Right Cessation
- 1978-12-21 CS CS788751A patent/CS210680B2/cs unknown
- 1978-12-21 FI FI783959A patent/FI783959A7/fi unknown
- 1978-12-21 GR GR57956A patent/GR72974B/el unknown
- 1978-12-21 AR AR274942A patent/AR222479A1/es active
- 1978-12-22 JP JP15773078A patent/JPS5492922A/ja active Pending
- 1978-12-22 IT IT31276/78A patent/IT1102755B/it active
- 1978-12-22 PT PT68978A patent/PT68978A/pt unknown
- 1978-12-22 DK DK581178A patent/DK581178A/da unknown
- 1978-12-22 LU LU80715A patent/LU80715A1/de unknown
- 1978-12-22 DE DE19782855786 patent/DE2855786A1/de not_active Withdrawn
- 1978-12-22 BR BR7808474A patent/BR7808474A/pt unknown
- 1978-12-22 EP EP78101826A patent/EP0002822B1/de not_active Expired
- 1978-12-22 ES ES476264A patent/ES476264A1/es not_active Expired
- 1978-12-22 DE DE7878101826T patent/DE2861980D1/de not_active Expired
- 1978-12-22 NO NO784354A patent/NO784354L/no unknown
- 1978-12-22 SE SE7813274A patent/SE7813274L/xx not_active Application Discontinuation
1979
- 1979-06-29 FR FR7916924A patent/FR2446838A1/fr not_active Withdrawn
- 1979-06-29 FR FR7916925A patent/FR2453867A1/fr not_active Withdrawn
- 1979-07-16 ES ES482504A patent/ES482504A1/es not_active Expired

Also Published As

Publication number	Publication date
CS210680B2 (en)	1982-01-29
JPS5492922A (en)	1979-07-23
IT7831276A0 (it)	1978-12-22
NL7812314A (nl)	1979-06-26
FR2453866A1 (fr)	1980-11-07
PT68978A (en)	1979-01-01
SE7813274L (sv)	1979-08-08
US4250085A (en)	1981-02-10
DE2855786A1 (de)	1979-07-05
EP0002822A1 (de)	1979-07-11
ES476264A1 (es)	1980-05-16
AR222479A1 (es)	1981-05-29
AT365166B (de)	1981-12-28
NZ189205A (en)	1982-03-23
LU80715A1 (de)	1980-07-21
ATA918478A (de)	1981-05-15
BR7808474A (pt)	1979-08-21
EP0002822B1 (de)	1982-07-28
FR2453867A1 (fr)	1980-11-07
ES482504A1 (es)	1980-04-01
AU4258178A (en)	1979-06-28
GR72974B (cs)	1984-01-20
FI783959A7 (fi)	1979-06-24
DE2861980D1 (en)	1982-09-16
MC1243A1 (fr)	1979-10-26
DK581178A (da)	1979-06-24
CA1108125A (en)	1981-09-01
IT1102755B (it)	1985-10-07
FR2446838A1 (fr)	1980-08-14
IL56241A0 (en)	1979-03-12

Publication	Publication Date	Title
US4016148A (en)	1977-04-05	Peptide derivatives of phosphonic and phosphinic acids and intermediates therefor
DE69232394T2 (de)	2002-08-22	Neue isosterische peptide
US5719296A (en)	1998-02-17	Pseudopeptide lactam inhibitors of peptide binding to MHC class II proteins
LU82567A1 (fr)	1981-02-03	Nouveaux tetra-ou pentapeptides,leur preparation et les medicaments qui les contiennent
EP0002822B1 (de)	1982-07-28	Phosphorhaltige Peptidderivate, deren Herstellung, Zwischenprodukte bei deren Herstellung und diese enthaltende pharmazeutische Präparate
SE438339B (sv)	1985-04-15	Forfarande for framstellning av foreningar med analgetisk verkan
DE3177306T2 (de)	1994-06-30	Verfahren und Verbindungen zur Herstellung von H-ARG-X-Z-Y-TYR-R.
AU2014392A (en)	1992-11-02	Anti-thrombotic peptides and pseudopeptides
US4128542A (en)	1978-12-05	Peptide derivatives
DE69426897T2 (de)	2001-07-05	Antithrombotisch wirkende azacycloalkyl-alkanoyl-peptide und-pseudopeptide
US4143134A (en)	1979-03-06	Halo-phosphonopeptides
US4421744A (en)	1983-12-20	Aminoacyl derivatives
SE452624B (sv)	1987-12-07	Sett att framstella n?722-arylsulfonyl-l-argininamider och farmaceutiskt godtagbara salter derav
DE2416428A1 (de)	1975-10-23	Tripeptide mit antidepressiver und prolactinausschuettender wirkung und verfahren zu ihrer herstellung
EP0203450B1 (de)	1992-04-01	Neue Derivate bicyclischer Aminosäuren, Verfahren zu ihrer Herstellung, diese enthaltende Mittel und deren Verwendung
NO784285L (no)	1979-06-21	Peptid-derivater og fremstilling av disse
CA1090785A (en)	1980-12-02	Peptide derivatives and process for the preparation thereof
DE2730524A1 (de)	1978-01-19	Peptidderivate und deren herstellung
HU198077B (en)	1989-07-28	Process for producing substituted aminoalkanoyl aminoalkylphosphonates
DE69922150T2 (de)	2005-12-01	Deoxyhypusin reagenz und peptide
JP3538453B2 (ja)	2004-06-14	ドーパミン遊離促進剤
GB2030148A (en)	1980-04-02	Peptide derivatives of phosphoric acids
US3749706A (en)	1973-07-31	Novel dipeptide amide and process for its manufacture
DE3877591T2 (de)	1993-05-19	Aminosaeure-derivate als antihypertensive.
SE438152B (sv)	1985-04-01	Forfarande for framstellning av substituerade fenylketoner med sedativ, muskelrelaxerande och antikonvulsiv verkan