CA2189690C - Nouveau principe actif peptidique et sa production - Google Patents

Nouveau principe actif peptidique et sa production Download PDF

Info

Publication number: CA2189690C
Authority: CA; Canada
Prior art keywords: val; pro; meval; terminus; nhbzl
Prior art date: 1994-05-06
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA002189690A

Other languages

English (en)

Other versions

CA2189690A1 (fr

Inventor

Wilhelm Amberg

Harald Bernard

Ernst Buschmann

Andreas Haupt

Lothar Janitschke

Bernd Janssen

Ulrich Karl

Andreas Kling

Stefan Muller

Bernd De Potzolli

Kurt Ritter

Marco Thyes

Thomas Zierke

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

AbbVie Deutschland GmbH and Co KG

Original Assignee

Abbott GmbH and Co KG

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.)

1994-05-06

Filing date

1995-04-26

Publication date

2007-06-19

1994-05-06 Priority claimed from DE4415997A external-priority patent/DE4415997A1/de

1995-04-26 Application filed by Abbott GmbH and Co KG filed Critical Abbott GmbH and Co KG

1995-11-16 Publication of CA2189690A1 publication Critical patent/CA2189690A1/fr

2007-06-19 Application granted granted Critical

2007-06-19 Publication of CA2189690C publication Critical patent/CA2189690C/fr

2015-04-26 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

108090000765 processed proteins & peptides Proteins 0.000 title description 8
238000002360 preparation method Methods 0.000 title description 7
150000001875 compounds Chemical class 0.000 claims abstract description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 23
238000000034 method Methods 0.000 claims description 17
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
150000008064 anhydrides Chemical class 0.000 claims description 10
WOXWRWOEURENTO-NSHDSACASA-N (2s)-n-benzylpyrrolidine-2-carboxamide Chemical compound O=C([C@H]1NCCC1)NCC1=CC=CC=C1 WOXWRWOEURENTO-NSHDSACASA-N 0.000 claims description 9
238000005859 coupling reaction Methods 0.000 claims description 9
-1 2-ethylhenyl Chemical group 0.000 claims description 8
239000002253 acid Substances 0.000 claims description 8
230000008878 coupling Effects 0.000 claims description 8
238000010168 coupling process Methods 0.000 claims description 8
125000006239 protecting group Chemical group 0.000 claims description 8
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 4
125000003277 amino group Chemical group 0.000 claims description 4
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
239000002243 precursor Substances 0.000 claims description 4
150000007513 acids Chemical class 0.000 claims description 2
229940125904 compound 1 Drugs 0.000 claims description 2
230000003301 hydrolyzing effect Effects 0.000 claims description 2
125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims 1
230000000118 anti-neoplastic effect Effects 0.000 abstract description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
239000000243 solution Substances 0.000 description 33
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
229940073584 methylene chloride Drugs 0.000 description 24
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
239000000203 mixture Substances 0.000 description 16
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 15
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
229910052739 hydrogen Inorganic materials 0.000 description 13
239000001257 hydrogen Substances 0.000 description 13
229960004592 isopropanol Drugs 0.000 description 11
239000002904 solvent Substances 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
239000008346 aqueous phase Substances 0.000 description 9
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
239000003054 catalyst Substances 0.000 description 8
238000005984 hydrogenation reaction Methods 0.000 description 8
239000012071 phase Substances 0.000 description 8
239000000047 product Substances 0.000 description 8
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
235000011167 hydrochloric acid Nutrition 0.000 description 7
229960000443 hydrochloric acid Drugs 0.000 description 7
238000002844 melting Methods 0.000 description 7
230000008018 melting Effects 0.000 description 7
229940086542 triethylamine Drugs 0.000 description 7
239000013543 active substance Substances 0.000 description 6
229940093499 ethyl acetate Drugs 0.000 description 6
235000019439 ethyl acetate Nutrition 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
239000000725 suspension Substances 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
239000002585 base Substances 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
230000006340 racemization Effects 0.000 description 5
239000000126 substance Substances 0.000 description 5
108010021889 valylvaline Proteins 0.000 description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
230000002378 acidificating effect Effects 0.000 description 4
238000000354 decomposition reaction Methods 0.000 description 4
150000003839 salts Chemical class 0.000 description 4
238000003756 stirring Methods 0.000 description 4
238000010626 work up procedure Methods 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000004821 distillation Methods 0.000 description 3
238000000605 extraction Methods 0.000 description 3
239000012065 filter cake Substances 0.000 description 3
239000008098 formaldehyde solution Substances 0.000 description 3
230000007935 neutral effect Effects 0.000 description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
238000005897 peptide coupling reaction Methods 0.000 description 3
238000005191 phase separation Methods 0.000 description 3
108010077112 prolyl-proline Proteins 0.000 description 3
239000007858 starting material Substances 0.000 description 3
SZNKRADUZXAHCO-MERQFXBCSA-N (2s)-n-benzylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.O=C([C@H]1NCCC1)NCC1=CC=CC=C1 SZNKRADUZXAHCO-MERQFXBCSA-N 0.000 description 2
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
101150041968 CDC13 gene Proteins 0.000 description 2
239000004215 Carbon black (E152) Substances 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
VKEQBMCRQDSRET-UHFFFAOYSA-N Methylone Chemical compound CNC(C)C(=O)C1=CC=C2OCOC2=C1 VKEQBMCRQDSRET-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
AKCRVYNORCOYQT-YFKPBYRVSA-N N-methyl-L-valine Chemical compound CN[C@@H](C(C)C)C(O)=O AKCRVYNORCOYQT-YFKPBYRVSA-N 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 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
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
238000011097 chromatography purification Methods 0.000 description 2
239000013078 crystal Substances 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
230000000694 effects Effects 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000007789 gas Substances 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
239000008188 pellet Substances 0.000 description 2
FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
102000004196 processed proteins & peptides Human genes 0.000 description 2
229960002429 proline Drugs 0.000 description 2
238000000746 purification Methods 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
238000010532 solid phase synthesis reaction Methods 0.000 description 2
229960004295 valine Drugs 0.000 description 2
239000004474 valine Substances 0.000 description 2
239000008096 xylene Substances 0.000 description 2
KPYXMALABCDPGN-HYOZMBHHSA-N (4s)-5-[[(2s)-6-amino-1-[[(2s,3s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2r)-1-[[2-[[2-[[(1s)-3-amino-1-carboxy-3-oxopropyl]amino]-2-oxoethyl]amino]-2-oxoethyl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]a Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN)CC1=CC=C(O)C=C1 KPYXMALABCDPGN-HYOZMBHHSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
WFSGQBNCVASPMW-UHFFFAOYSA-N 2-ethylhexanoyl chloride Chemical compound CCCCC(CC)C(Cl)=O WFSGQBNCVASPMW-UHFFFAOYSA-N 0.000 description 1
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
101100515517 Arabidopsis thaliana XI-I gene Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
206010025323 Lymphomas Diseases 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
APGLTERDKORUHK-LURJTMIESA-N N,N-dimethyl-L-Valine Chemical compound CC(C)[C@H](N(C)C)C(O)=O APGLTERDKORUHK-LURJTMIESA-N 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
239000007832 Na2SO4 Substances 0.000 description 1
229930040373 Paraformaldehyde Natural products 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
KRNYOVHEKOBTEF-YUMQZZPRSA-N Val-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(O)=O KRNYOVHEKOBTEF-YUMQZZPRSA-N 0.000 description 1
229960000583 acetic acid Drugs 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
210000000481 breast Anatomy 0.000 description 1
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000007257 deesterification reaction Methods 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000012458 free base Substances 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
XRKQMIFKHDXFNQ-UHFFFAOYSA-N n-cyclohexyl-n-ethylcyclohexanamine Chemical compound C1CCCCC1N(CC)C1CCCCC1 XRKQMIFKHDXFNQ-UHFFFAOYSA-N 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000001613 neoplastic effect Effects 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
231100000614 poison Toxicity 0.000 description 1
230000007096 poisonous effect Effects 0.000 description 1
235000013930 proline Nutrition 0.000 description 1
210000002307 prostate Anatomy 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
239000013557 residual solvent Substances 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000007787 solid Substances 0.000 description 1
238000001694 spray drying Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
210000004291 uterus Anatomy 0.000 description 1
238000010792 warming Methods 0.000 description 1
239000002699 waste material Substances 0.000 description 1

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
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/101—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
- 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
- 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)
Genetics & Genomics (AREA)
Biochemistry (AREA)
Biophysics (AREA)
General Health & Medical Sciences (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Life Sciences & Earth Sciences (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

CA002189690A 1994-05-06 1995-04-26 Nouveau principe actif peptidique et sa production Expired - Fee Related CA2189690C (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DE4415997A DE4415997A1 (de)	1994-05-06	1994-05-06	Neuer peptidischer Wirkstoff und dessen Herstellung
DEP4415997.8		1994-05-06
PCT/EP1995/001577 WO1995030691A1 (fr)	1994-05-06	1995-04-26	Nouveau principe actif peptidique et sa production

Publications (2)

Publication Number	Publication Date
CA2189690A1 CA2189690A1 (fr)	1995-11-16
CA2189690C true CA2189690C (fr)	2007-06-19

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Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002189690A Expired - Fee Related CA2189690C (fr)	1994-05-06	1995-04-26	Nouveau principe actif peptidique et sa production

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CA (1)	CA2189690C (fr)

1995
- 1995-04-26 CA CA002189690A patent/CA2189690C/fr not_active Expired - Fee Related

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Publication number	Publication date
CA2189690A1 (fr)	1995-11-16

Legal Events

Date	Code	Title	Description
2002-04-03	EEER	Examination request
2015-06-08	MKLA	Lapsed	Effective date: 20150427

Publication	Publication Date	Title
CA1329445C (fr)	1994-05-10	Procede pour la preparation de la n-[1(s)-ethylcarbonyl-3- phenylpropoxy]-l-alanyl-l-proline
US4368192A (en)	1983-01-11	Peptides
IE60128B1 (en)	1994-06-01	Hydroxylamine derivatives,their preparation and use as medicaments
EP0098865B1 (fr)	1989-03-01	Synthese de peptides et agents de blocage d'acides amines
WO1993021176A1 (fr)	1993-10-28	Nouveaux acides amines cycliques et leurs derives
US5864012A (en)	1999-01-26	Active peptide and its preparation
CA2189690C (fr)	2007-06-19	Nouveau principe actif peptidique et sa production
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CA2223911C (fr)	2009-03-24	La preparation de peptides actifs
EP0001174B1 (fr)	1981-08-12	Un peptide et ses sels, procédés pour leur préparation et les compositions les contenant
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Natchev	0	Organophosphorous Analogues and Derivatives of the Natural l-Amino Carboxylic Acids and Peptides. V. 1'Synthesis of Analogues of Plumbemycin A
JPH04360898A (ja)	1992-12-14	生理活性ペンタペプチドの製法
JPH09255666A (ja)	1997-09-30	ピペラジンアミド化合物及びピペラジンアミド誘導体の製造方法
HU179926B (hu)	1983-01-28	Eljárás a gasztrin C-terminális tetrapeptid-szekvenciájának előállítására