SK285387B6 - Spôsob prípravy cyklo(Asp-DPhe-NMeVal-Arg-Gly) - Google Patents

Spôsob prípravy cyklo(Asp-DPhe-NMeVal-Arg-Gly) Download PDF

Info

Publication number: SK285387B6
Authority: SK; Slovakia
Prior art keywords: dphe; asp; arg; nmeval; gly
Prior art date: 1999-03-11

Application number

SK1255-2001A

Other languages

English (en)

Slovak (sk)

Other versions

SK12552001A3 (sk

Inventor

Alfred Jonczyk

Markus Arnold

Original Assignee

Merck Patent Gmbh

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.)

1999-03-11

Filing date

2000-03-01

Publication date

2006-12-07

2000-03-01 Application filed by Merck Patent Gmbh filed Critical Merck Patent Gmbh

2002-05-09 Publication of SK12552001A3 publication Critical patent/SK12552001A3/sk

2006-12-07 Publication of SK285387B6 publication Critical patent/SK285387B6/sk

Links

238000004519 manufacturing process Methods 0.000 title abstract 2
125000006239 protecting group Chemical group 0.000 claims abstract description 41
AMLYAMJWYAIXIA-VWNVYAMZSA-N cilengitide Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C(C)C)N(C)C(=O)[C@H]1CC1=CC=CC=C1 AMLYAMJWYAIXIA-VWNVYAMZSA-N 0.000 claims abstract description 16
ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims abstract description 15
150000003839 salts Chemical class 0.000 claims abstract description 13
125000004122 cyclic group Chemical group 0.000 claims abstract description 8
238000003786 synthesis reaction Methods 0.000 claims description 27
230000015572 biosynthetic process Effects 0.000 claims description 26
238000000034 method Methods 0.000 claims description 23
238000006243 chemical reaction Methods 0.000 claims description 20
108090000765 processed proteins & peptides Proteins 0.000 claims description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
108010016626 Dipeptides Proteins 0.000 claims description 5
RRONHWAVOYADJL-OAHLLOKOSA-N (2r)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 RRONHWAVOYADJL-OAHLLOKOSA-N 0.000 claims description 4
238000009833 condensation Methods 0.000 claims description 4
230000005494 condensation Effects 0.000 claims description 4
150000004702 methyl esters Chemical class 0.000 claims description 4
238000010511 deprotection reaction Methods 0.000 claims description 3
239000012634 fragment Substances 0.000 claims description 3
239000000543 intermediate Substances 0.000 claims description 3
-1 amino, carboxyl Chemical group 0.000 description 27
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 18
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
239000002904 solvent Substances 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
150000001413 amino acids Chemical class 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
235000001014 amino acid Nutrition 0.000 description 9
239000000203 mixture Substances 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
125000002252 acyl group Chemical group 0.000 description 7
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
SOHLZANWVLCPHK-LBPRGKRZSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxo-4-phenylmethoxybutanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC(=O)OCC1=CC=CC=C1 SOHLZANWVLCPHK-LBPRGKRZSA-N 0.000 description 6
GVIXTVCDNCXXSH-AWEZNQCLSA-N (2s)-2-amino-5-[[amino-[(2,2,4,6,7-pentamethyl-3h-1-benzofuran-5-yl)sulfonylamino]methylidene]amino]pentanoic acid Chemical compound OC(=O)[C@@H](N)CCCN=C(N)NS(=O)(=O)C1=C(C)C(C)=C2OC(C)(C)CC2=C1C GVIXTVCDNCXXSH-AWEZNQCLSA-N 0.000 description 6
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
238000010647 peptide synthesis reaction Methods 0.000 description 6
102000004196 processed proteins & peptides Human genes 0.000 description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 5
229910052739 hydrogen Inorganic materials 0.000 description 5
239000001257 hydrogen Substances 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
235000011007 phosphoric acid Nutrition 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
239000012317 TBTU Substances 0.000 description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
125000003710 aryl alkyl group Chemical group 0.000 description 4
125000003118 aryl group Chemical group 0.000 description 4
235000003704 aspartic acid Nutrition 0.000 description 4
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 4
235000019253 formic acid Nutrition 0.000 description 4
239000000047 product Substances 0.000 description 4
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 4
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
102000001189 Cyclic Peptides Human genes 0.000 description 3
108010069514 Cyclic Peptides Proteins 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-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
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000002253 acid Substances 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
229910000147 aluminium phosphate Inorganic materials 0.000 description 3
125000003435 aroyl group Chemical group 0.000 description 3
238000003776 cleavage reaction Methods 0.000 description 3
230000008878 coupling Effects 0.000 description 3
238000010168 coupling process Methods 0.000 description 3
238000005859 coupling reaction Methods 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
239000002243 precursor Substances 0.000 description 3
238000007363 ring formation reaction Methods 0.000 description 3
230000007017 scission Effects 0.000 description 3
229910000029 sodium carbonate Inorganic materials 0.000 description 3
239000007790 solid phase Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
125000005092 alkenyloxycarbonyl group Chemical group 0.000 description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
125000005161 aryl oxy carbonyl group Chemical group 0.000 description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
125000002843 carboxylic acid group Chemical group 0.000 description 2
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 2
DLLHGHUMLSLOID-RGMNGODLSA-N methyl (2s)-3-methyl-2-(methylamino)butanoate;hydrochloride Chemical compound Cl.CN[C@@H](C(C)C)C(=O)OC DLLHGHUMLSLOID-RGMNGODLSA-N 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
239000007787 solid Substances 0.000 description 2
229960002317 succinimide Drugs 0.000 description 2
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 2
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 2
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
OIXLLKLZKCBCPS-RZVRUWJTSA-N (2s)-2-azanyl-5-[bis(azanyl)methylideneamino]pentanoic acid Chemical compound OC(=O)[C@@H](N)CCCNC(N)=N.OC(=O)[C@@H](N)CCCNC(N)=N OIXLLKLZKCBCPS-RZVRUWJTSA-N 0.000 description 1
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
UEIZUEWXLJOVLD-UHFFFAOYSA-N 3-(1-methylpyrrolidin-3-yl)pyridine Chemical compound C1N(C)CCC1C1=CC=CN=C1 UEIZUEWXLJOVLD-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
125000003974 3-carbamimidamidopropyl group Chemical group C(N)(=N)NCCC* 0.000 description 1
229960000549 4-dimethylaminophenol Drugs 0.000 description 1
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 1
244000248349 Citrus limon Species 0.000 description 1
235000005979 Citrus limon Nutrition 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
101000797623 Homo sapiens Protein AMBP Proteins 0.000 description 1
101000911790 Homo sapiens Sister chromatid cohesion protein DCC1 Proteins 0.000 description 1
102400001240 Inter-alpha-trypsin inhibitor light chain Human genes 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
VGALFAWDSNRXJK-VIFPVBQESA-N L-aspartic acid beta-benzyl ester Chemical compound OC(=O)[C@@H](N)CC(=O)OCC1=CC=CC=C1 VGALFAWDSNRXJK-VIFPVBQESA-N 0.000 description 1
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
102100027040 Sister chromatid cohesion protein DCC1 Human genes 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
LDKDGDIWEUUXSH-UHFFFAOYSA-N Thymophthalein Chemical compound C1=C(O)C(C(C)C)=CC(C2(C3=CC=CC=C3C(=O)O2)C=2C(=CC(O)=C(C(C)C)C=2)C)=C1C LDKDGDIWEUUXSH-UHFFFAOYSA-N 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
GELXFVQAWNTGPQ-UHFFFAOYSA-N [N].C1=CNC=N1 Chemical compound [N].C1=CNC=N1 GELXFVQAWNTGPQ-UHFFFAOYSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
JIMXXGFJRDUSRO-UHFFFAOYSA-N adamantane-1-carboxylic acid Chemical compound C1C(C2)CC3CC2CC1(C(=O)O)C3 JIMXXGFJRDUSRO-UHFFFAOYSA-N 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
125000002723 alicyclic group Chemical group 0.000 description 1
125000005103 alkyl silyl group Chemical group 0.000 description 1
HXXFSFRBOHSIMQ-VFUOTHLCSA-N alpha-D-glucose 1-phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(O)=O)[C@H](O)[C@@H](O)[C@@H]1O HXXFSFRBOHSIMQ-VFUOTHLCSA-N 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 1
125000004391 aryl sulfonyl group Chemical group 0.000 description 1
125000001743 benzylic group Chemical group 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
125000005518 carboxamido group Chemical group 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
239000012141 concentrate Chemical group 0.000 description 1
NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
RMGVZKRVHHSUIM-UHFFFAOYSA-N dithionic acid Chemical compound OS(=O)(=O)S(O)(=O)=O RMGVZKRVHHSUIM-UHFFFAOYSA-N 0.000 description 1
238000001035 drying Methods 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
229950010772 glucose-1-phosphate Drugs 0.000 description 1
ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
LLYKPZOWCPVRPD-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine;n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=CC=N1 LLYKPZOWCPVRPD-UHFFFAOYSA-N 0.000 description 1
229960002715 nicotine Drugs 0.000 description 1
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
VWBWQOUWDOULQN-UHFFFAOYSA-N nmp n-methylpyrrolidone Chemical compound CN1CCCC1=O.CN1CCCC1=O VWBWQOUWDOULQN-UHFFFAOYSA-N 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
238000005457 optimization Methods 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
229910000343 potassium bisulfate Inorganic materials 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
125000000542 sulfonic acid group Chemical group 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
SJMDMGHPMLKLHQ-UHFFFAOYSA-N tert-butyl 2-aminoacetate Chemical compound CC(C)(C)OC(=O)CN SJMDMGHPMLKLHQ-UHFFFAOYSA-N 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
125000005425 toluyl group Chemical group 0.000 description 1
239000005051 trimethylchlorosilane Substances 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
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
125000005500 uronium group Chemical group 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- 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
- C07K5/06086—Dipeptides with the first amino acid being basic
- C07K5/06095—Arg-amino acid
- 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
- C07K5/0819—Tripeptides with the first amino acid being acidic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Biophysics (AREA)
Biochemistry (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

SK1255-2001A 1999-03-11 2000-03-01 Spôsob prípravy cyklo(Asp-DPhe-NMeVal-Arg-Gly) SK285387B6 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19910727		1999-03-11
PCT/EP2000/001751 WO2000053627A1 (de)	1999-03-11	2000-03-01	VERFAHREN ZUR HERSTELLUNG VON CYCLO-(Asp-DPhe-NMeVal-Arg-Gly)

Publications (2)

Publication Number	Publication Date
SK12552001A3 SK12552001A3 (sk)	2002-05-09
SK285387B6 true SK285387B6 (sk)	2006-12-07

Family

ID=7900511

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1255-2001A SK285387B6 (sk)	1999-03-11	2000-03-01	Spôsob prípravy cyklo(Asp-DPhe-NMeVal-Arg-Gly)

Country Status (28)

Country	Link
US (1)	US6822074B1 (pl)
EP (1)	EP1159296B1 (pl)
JP (1)	JP4762418B2 (pl)
KR (1)	KR100645002B1 (pl)
CN (1)	CN1200947C (pl)
AR (1)	AR022905A1 (pl)
AT (1)	ATE267839T1 (pl)
AU (1)	AU762540B2 (pl)
BR (1)	BR0008863A (pl)
CA (1)	CA2366694C (pl)
CZ (1)	CZ299879B6 (pl)
DE (1)	DE50006598D1 (pl)
DK (1)	DK1159296T3 (pl)
ES (1)	ES2221616T3 (pl)
HK (1)	HK1044780B (pl)
HU (1)	HUP0200369A3 (pl)
ID (1)	ID30126A (pl)
MY (1)	MY120083A (pl)
NO (1)	NO330030B1 (pl)
PL (1)	PL202996B1 (pl)
PT (1)	PT1159296E (pl)
RU (1)	RU2243974C2 (pl)
SE (1)	SE1159296T5 (pl)
SK (1)	SK285387B6 (pl)
TW (1)	TWI269798B (pl)
UA (1)	UA71608C2 (pl)
WO (1)	WO2000053627A1 (pl)
ZA (1)	ZA200108335B (pl)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB0814519D0 (en)	2008-08-08	2008-09-17	Imp Innovations Ltd	Process
CA2761622A1 (en) *	2009-05-15	2010-11-18	National Research Council Of Canada	Dna sequences encoding caryophyllaceae and caryophyllaceae-like cyclopeptide precursors and methods of use
AU2010251385B2 (en) *	2009-05-20	2016-04-14	Merck Patent Gmbh	Novel solid materials of {[2S, 5R,8S,11S)-5-benzyl-11-(3-guanidino-propyl)-8-isopropyl-7-methyl-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaaza-cyclopentadec-2-yl]-acetic acid} and methods for obtaining them
JP5946770B2 (ja)	2009-12-10	2016-07-06	メルクパテントゲゼルシャフトミットベシュレンクテルハフツングＭｅｒｃｋＰａｔｅｎｔＧｅｓｅｌｌｓｃｈａｆｔｍｉｔｂｅｓｃｈｒａｅｎｋｔｅｒＨａｆｔｕｎｇ	オリゴペプチドを含む医薬組成物
WO2012167870A1 (en)	2011-06-09	2012-12-13	Merck Patent Gmbh	Treatment of cancers and metastases with suspensions of cilengitide in carrier
EP3802559A1 (en) *	2018-06-05	2021-04-14	DSM IP Assets B.V.	Methods for the synthesis of arginine-containing peptides

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1038741B (de) *	1956-09-14	1958-09-11	Eberhard Brecklinghaus	Aus Gummi oder einem anderen elastischen Werkstoff bestehender Kantenschoner fuer Treppenstufen aus Beton od. dgl.
US3630660A (en) *	1968-10-31	1971-12-28	Burlington Industries Inc	Process for removal of moisture and/or solvents from textile materials
UA43823C2 (uk) *	1992-07-06	2002-01-15	Мерк Патент Геселлшафт Міт Бесшренктер Хафтунг	ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ ДЛЯ ІНГІБУВАННЯ ІНТЕГРИН <font face="Symbol">a</font><sub>V</sub><font face="Symbol">b</font><sub>3</sub>-ОПОСЕРЕДКОВАНОЇ КЛІТИННОЇ АДГЕЗІЇ КЛІТИН ССАВЦІВ, СПОСІБ ЛІКУВАННЯ ТА ПРОФІЛАКТИКИ ЗАХВОРЮВАННЯ, АСОЦІЙОВАНОГО З ПОРУШЕННЯМ АДГЕЗІЇ КЛІТИН, СПОСІБ БЛОКУВАННЯ ЗВ'ЯЗУВАННЯ ФІБРИНОГЕНОМ ІНТЕГРИНУ, КОМПОЗИЦІЯ ДЛЯ ЗАГОЄННЯ РАН
JPH06263798A (ja) *	1993-01-13	1994-09-20	Takeda Chem Ind Ltd	βターン及びγターンを有する環状ペンタペプチド、その製造方法および用途
DE69418353T2 (de) *	1993-01-13	1999-10-28	Takeda Chemical Industries, Ltd.	Cyclische Pentapeptide mit Beta-Turn und Gamma-Turn
DE4310643A1 (de) *	1993-04-01	1994-10-06	Merck Patent Gmbh	Cyclische Adhäsionsinhibitoren
WO1995033769A1 (de)	1994-06-02	1995-12-14	Boehringer Mannheim Gmbh	Verfahren zur herstellung von cardiodilatin-fragmenten, hochgereinigte cardiodilatin-fragmente und zwischenprodukte zu deren herstellung
DE19534177A1 (de) *	1995-09-15	1997-03-20	Merck Patent Gmbh	Cyclische Adhäsionsinhibitoren
DE19538741A1 (de)	1995-10-18	1997-04-24	Merck Patent Gmbh	Cyclopeptidderivate
DE19613933A1 (de)	1996-04-06	1997-10-09	Merck Patent Gmbh	Cyclische Adhäsionsinhibitoren
CA2256543C (en) *	1996-05-31	2010-12-07	The Scripps Research Institute	Methods and compositions useful for inhibition of angiogenesis
DE19728524A1 (de) *	1997-07-04	1999-01-07	Merck Patent Gmbh	Cyclische Azapeptide

2000
- 2000-01-03 UA UA2001106897A patent/UA71608C2/uk unknown
- 2000-03-01 JP JP2000604062A patent/JP4762418B2/ja not_active Expired - Fee Related
- 2000-03-01 HU HU0200369A patent/HUP0200369A3/hu unknown
- 2000-03-01 HK HK02106365.2A patent/HK1044780B/zh not_active IP Right Cessation
- 2000-03-01 BR BR0008863-3A patent/BR0008863A/pt active Search and Examination
- 2000-03-01 DE DE50006598T patent/DE50006598D1/de not_active Expired - Lifetime
- 2000-03-01 SK SK1255-2001A patent/SK285387B6/sk not_active IP Right Cessation
- 2000-03-01 CZ CZ20013214A patent/CZ299879B6/cs not_active IP Right Cessation
- 2000-03-01 WO PCT/EP2000/001751 patent/WO2000053627A1/de not_active Ceased
- 2000-03-01 MY MYPI20000799A patent/MY120083A/en unknown
- 2000-03-01 ES ES00920461T patent/ES2221616T3/es not_active Expired - Lifetime
- 2000-03-01 US US09/936,230 patent/US6822074B1/en not_active Expired - Fee Related
- 2000-03-01 KR KR1020017011291A patent/KR100645002B1/ko not_active Expired - Fee Related
- 2000-03-01 EP EP00920461A patent/EP1159296B1/de not_active Expired - Lifetime
- 2000-03-01 AU AU41034/00A patent/AU762540B2/en not_active Ceased
- 2000-03-01 SE SE00820481T patent/SE1159296T5/xx unknown
- 2000-03-01 CN CNB008048746A patent/CN1200947C/zh not_active Expired - Fee Related
- 2000-03-01 CA CA2366694A patent/CA2366694C/en not_active Expired - Fee Related
- 2000-03-01 RU RU2001126541/04A patent/RU2243974C2/ru not_active IP Right Cessation
- 2000-03-01 PT PT00920461T patent/PT1159296E/pt unknown
- 2000-03-01 ID IDW00200102095A patent/ID30126A/id unknown
- 2000-03-01 PL PL349646A patent/PL202996B1/pl not_active IP Right Cessation
- 2000-03-01 AT AT00920461T patent/ATE267839T1/de active
- 2000-03-01 DK DK00920461T patent/DK1159296T3/da active
- 2000-03-07 TW TW089104103A patent/TWI269798B/zh not_active IP Right Cessation
- 2000-03-10 AR ARP000101079A patent/AR022905A1/es active IP Right Grant
2001
- 2001-09-10 NO NO20014383A patent/NO330030B1/no not_active IP Right Cessation
- 2001-10-10 ZA ZA200108335A patent/ZA200108335B/en unknown

Also Published As

Publication number	Publication date
EP1159296B1 (de)	2004-05-26
CZ20013214A3 (cs)	2001-12-12
UA71608C2 (en)	2004-12-15
CN1343220A (zh)	2002-04-03
AU4103400A (en)	2000-09-28
JP4762418B2 (ja)	2011-08-31
AU762540B2 (en)	2003-06-26
NO20014383D0 (no)	2001-09-10
WO2000053627A1 (de)	2000-09-14
ATE267839T1 (de)	2004-06-15
HUP0200369A2 (en)	2002-06-29
US6822074B1 (en)	2004-11-23
HK1044780B (zh)	2005-08-26
NO330030B1 (no)	2011-02-07
KR20010102503A (ko)	2001-11-15
ZA200108335B (en)	2003-01-10
CA2366694C (en)	2010-07-20
ID30126A (id)	2001-11-08
SE1159296T3 (pl)	2004-08-24
PT1159296E (pt)	2004-10-29
TWI269798B (en)	2007-01-01
CZ299879B6 (cs)	2008-12-17
MY120083A (en)	2005-08-30
RU2243974C2 (ru)	2005-01-10
BR0008863A (pt)	2002-01-02
HK1044780A1 (en)	2002-11-01
DE50006598D1 (de)	2004-07-01
SE1159296T5 (pl)	2004-09-07
CA2366694A1 (en)	2000-09-14
PL202996B1 (pl)	2009-08-31
HUP0200369A3 (en)	2002-09-30
KR100645002B1 (ko)	2006-11-10
NO20014383L (no)	2001-11-02
EP1159296A1 (de)	2001-12-05
JP2002539137A (ja)	2002-11-19
CN1200947C (zh)	2005-05-11
ES2221616T3 (es)	2005-01-01
AR022905A1 (es)	2002-09-04
DK1159296T3 (da)	2004-09-27
SK12552001A3 (sk)	2002-05-09

Legal Events

Date	Code	Title	Description
2014-12-04	MM4A	Patent lapsed due to non-payment of maintenance fees	Effective date: 20140301

Publication	Publication Date	Title
US9346850B2 (en)	2016-05-24	Method of producing peptide
ES2606753T3 (es)	2017-03-27	Procedimiento para la fabricación de Degarelix y sus intermedios
US9260480B2 (en)	2016-02-16	Process for the manufacture of Degarelix and its intermediates
US5977302A (en)	1999-11-02	Liquid phase process for the preparation of GnRH peptides
ES2885869T3 (es)	2021-12-15	Procedimiento para la fabricación de degarelix y sus productos intermedios
US9850285B2 (en)	2017-12-26	Process for preparing eptifibatide
JPH0354957B2 (pl)	1991-08-21
SK285387B6 (sk)	2006-12-07	Spôsob prípravy cyklo(Asp-DPhe-NMeVal-Arg-Gly)
US7999068B2 (en)	2011-08-16	Process for the preparation of bicyclic peptide compounds
US7262169B1 (en)	2007-08-28	Process for preparing peptide intermediates
MXPA01009111A (es)	2002-05-09	Procedimiento para preparar ciclo (asp-dfen-nmeval-arg-gli)
FI77874B (fi)	1989-01-31	Foerfarande foer framstaellning av nya, terapeutiskt anvaendbara peptider.
JPH07316193A (ja)	1995-12-05	ペプチド誘導体およびその用途
CN119823209A (zh)	2025-04-15	一种含马来酰亚胺酸的环肽合成方法
昧人	0	SeeeSS SS