UA71608C2 - A method for producing the cyclic pentapeptide - Google Patents

A method for producing the cyclic pentapeptide Download PDF

Info

Publication number: UA71608C2
Authority: UA; Ukraine
Prior art keywords: azr; orpe; aga; siu; mmema
Prior art date: 1999-03-11

Application number

UA2001106897A

Other languages

English (en)

Ukrainian (uk)

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

2000-01-03

Publication date

2004-12-15

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

2004-12-15 Publication of UA71608C2 publication Critical patent/UA71608C2/uk

Links

125000004122 cyclic group Chemical group 0.000 title claims abstract description 9
238000004519 manufacturing process Methods 0.000 title abstract 2
125000006239 protecting group Chemical group 0.000 claims abstract description 45
150000003839 salts Chemical class 0.000 claims abstract description 12
230000015572 biosynthetic process Effects 0.000 claims description 28
238000003786 synthesis reaction Methods 0.000 claims description 27
238000000034 method Methods 0.000 claims description 25
238000006243 chemical reaction Methods 0.000 claims description 22
108090000765 processed proteins & peptides Proteins 0.000 claims description 11
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
125000003277 amino group Chemical group 0.000 claims description 7
238000007363 ring formation reaction Methods 0.000 claims description 7
108010016626 Dipeptides Proteins 0.000 claims description 5
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 4
238000009833 condensation Methods 0.000 claims description 3
230000005494 condensation Effects 0.000 claims description 3
239000012634 fragment Substances 0.000 claims description 3
230000009466 transformation Effects 0.000 claims description 2
150000001875 compounds Chemical class 0.000 claims 1
239000000543 intermediate Substances 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 abstract 1
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 abstract 1
-1 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl Chemical group 0.000 description 21
239000000243 solution Substances 0.000 description 18
239000002904 solvent Substances 0.000 description 15
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 14
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
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239000002244 precipitate Substances 0.000 description 11
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125000002252 acyl group Chemical group 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
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239000002253 acid 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
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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
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235000003704 aspartic acid Nutrition 0.000 description 5
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 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
238000003756 stirring Methods 0.000 description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
239000012317 TBTU Substances 0.000 description 4
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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 4
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125000003710 aryl alkyl group Chemical group 0.000 description 4
125000003118 aryl group Chemical group 0.000 description 4
IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
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239000007790 solid phase Substances 0.000 description 4
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125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
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239000003153 chemical reaction reagent Substances 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
235000019253 formic acid Nutrition 0.000 description 3
ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
239000013067 intermediate product Substances 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
239000002243 precursor Substances 0.000 description 3
239000012047 saturated solution Substances 0.000 description 3
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
239000004475 Arginine Substances 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
102000001189 Cyclic Peptides Human genes 0.000 description 2
108010069514 Cyclic Peptides Proteins 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
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UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
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KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
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125000002723 alicyclic group Chemical group 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
125000005092 alkenyloxycarbonyl group Chemical group 0.000 description 2
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239000008346 aqueous phase Substances 0.000 description 2
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238000004090 dissolution Methods 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
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125000000623 heterocyclic group Chemical group 0.000 description 2
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125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
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CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
FPIQZBQZKBKLEI-UHFFFAOYSA-N ethyl 1-[[2-chloroethyl(nitroso)carbamoyl]amino]cyclohexane-1-carboxylate Chemical compound ClCCN(N=O)C(=O)NC1(C(=O)OCC)CCCCC1 FPIQZBQZKBKLEI-UHFFFAOYSA-N 0.000 description 1
210000000720 eyelash Anatomy 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
229950010772 glucose-1-phosphate Drugs 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 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
WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
229960003512 nicotinic acid Drugs 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 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
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-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
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
235000013930 proline Nutrition 0.000 description 1
235000019260 propionic acid Nutrition 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
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000010532 solid phase synthesis reaction Methods 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
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 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
125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
125000005425 toluyl group Chemical group 0.000 description 1
230000001131 transforming effect Effects 0.000 description 1
125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
WVLBCYQITXONBZ-UHFFFAOYSA-N trimethyl phosphate Chemical compound COP(=O)(OC)OC WVLBCYQITXONBZ-UHFFFAOYSA-N 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
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)

UA2001106897A 1999-03-11 2000-01-03 A method for producing the cyclic pentapeptide UA71608C2 (en)

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 (1)

Publication Number	Publication Date
UA71608C2 true UA71608C2 (en)	2004-12-15

Family

ID=7900511

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA2001106897A UA71608C2 (en)	1999-03-11	2000-01-03	A method for producing the cyclic pentapeptide

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
EP2430162A4 (en) *	2009-05-15	2013-04-24	Ca Nat Research Council	DNA SEQUENCES AND METHOD OF PROCESSING ENCODING CARYOPHYLLACEAE AND CARYOPHYLLACEAE-SIMILAR CYCLOPEPTIDE TREATMENTS
EP3085704A1 (en) *	2009-05-20	2016-10-26	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
PE20121359A1 (es)	2009-12-10	2012-10-15	Merck Patent Gmbh	Composicion farmaceutica que comprende oligopeptidos
EP2717854B1 (en)	2011-06-09	2019-01-16	Merck Patent GmbH	Treatment of cancers and metastases with suspensions of cilengitide in carrier
WO2019234108A1 (en) *	2018-06-05	2019-12-12	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
EP0606881B1 (en) *	1993-01-13	1999-05-12	Takeda Chemical Industries, Ltd.	Cyclic pentapeptides having a beta-turn and a gamma-turn
DE4310643A1 (de)	1993-04-01	1994-10-06	Merck Patent Gmbh	Cyclische Adhäsionsinhibitoren
AU2671795A (en) *	1994-06-02	1996-01-04	Boehringer Mannheim Gmbh	Process and intermediate products for preparing cardiodilatin fragments, and highly purified cardiodilatin fragments
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
EP0951295B1 (en) *	1996-05-31	2010-06-09	The Scripps Research Institute	Compositions for use in inhibiting of alpha-v-beta3 mediated 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 ES ES00920461T patent/ES2221616T3/es not_active Expired - Lifetime
- 2000-03-01 SK SK1255-2001A patent/SK285387B6/sk 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 WO PCT/EP2000/001751 patent/WO2000053627A1/de not_active Ceased
- 2000-03-01 AU AU41034/00A patent/AU762540B2/en not_active Ceased
- 2000-03-01 CA CA2366694A patent/CA2366694C/en not_active Expired - Fee Related
- 2000-03-01 HK HK02106365.2A patent/HK1044780B/zh not_active IP Right Cessation
- 2000-03-01 EP EP00920461A patent/EP1159296B1/de not_active Expired - Lifetime
- 2000-03-01 DK DK00920461T patent/DK1159296T3/da active
- 2000-03-01 KR KR1020017011291A patent/KR100645002B1/ko not_active Expired - Fee Related
- 2000-03-01 JP JP2000604062A patent/JP4762418B2/ja not_active Expired - Fee Related
- 2000-03-01 SE SE00820481T patent/SE1159296T5/xx unknown
- 2000-03-01 HU HU0200369A patent/HUP0200369A3/hu unknown
- 2000-03-01 CZ CZ20013214A patent/CZ299879B6/cs not_active IP Right Cessation
- 2000-03-01 MY MYPI20000799A patent/MY120083A/en unknown
- 2000-03-01 CN CNB008048746A patent/CN1200947C/zh not_active Expired - Fee Related
- 2000-03-01 PL PL349646A patent/PL202996B1/pl 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 AT AT00920461T patent/ATE267839T1/de active
- 2000-03-01 RU RU2001126541/04A patent/RU2243974C2/ru not_active IP Right Cessation
- 2000-03-01 US US09/936,230 patent/US6822074B1/en not_active Expired - Fee Related
- 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
RU2243974C2 (ru)	2005-01-10
AU4103400A (en)	2000-09-28
ZA200108335B (en)	2003-01-10
CZ20013214A3 (cs)	2001-12-12
KR100645002B1 (ko)	2006-11-10
HUP0200369A3 (en)	2002-09-30
MY120083A (en)	2005-08-30
HK1044780A1 (en)	2002-11-01
SK12552001A3 (sk)	2002-05-09
WO2000053627A1 (de)	2000-09-14
DE50006598D1 (de)	2004-07-01
CA2366694C (en)	2010-07-20
PL202996B1 (pl)	2009-08-31
TWI269798B (en)	2007-01-01
NO20014383D0 (no)	2001-09-10
EP1159296B1 (de)	2004-05-26
HUP0200369A2 (en)	2002-06-29
HK1044780B (zh)	2005-08-26
SK285387B6 (sk)	2006-12-07
KR20010102503A (ko)	2001-11-15
JP4762418B2 (ja)	2011-08-31
AR022905A1 (es)	2002-09-04
CN1343220A (zh)	2002-04-03
SE1159296T5 (pl)	2004-09-07
DK1159296T3 (da)	2004-09-27
BR0008863A (pt)	2002-01-02
EP1159296A1 (de)	2001-12-05
SE1159296T3 (pl)	2004-08-24
PT1159296E (pt)	2004-10-29
NO330030B1 (no)	2011-02-07
US6822074B1 (en)	2004-11-23
CZ299879B6 (cs)	2008-12-17
ES2221616T3 (es)	2005-01-01
JP2002539137A (ja)	2002-11-19
CA2366694A1 (en)	2000-09-14
ID30126A (id)	2001-11-08
CN1200947C (zh)	2005-05-11
AU762540B2 (en)	2003-06-26
ATE267839T1 (de)	2004-06-15
NO20014383L (no)	2001-11-02

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