SK10842002A3 - Spôsob prípravy acetyl-amidiniofenylalanyl-cyklohexylglycyl- pyridinioalanínamidov a medziprodukty používané pri tomto spôsobe - Google Patents

Spôsob prípravy acetyl-amidiniofenylalanyl-cyklohexylglycyl- pyridinioalanínamidov a medziprodukty používané pri tomto spôsobe Download PDF

Info

Publication number: SK10842002A3
Authority: SK; Slovakia
Prior art keywords: formula; compound; salt; acid; reaction
Prior art date: 2000-01-28

Application number

SK1084-2002A

Other languages

English (en)

Slovak (sk)

Inventor

Gerhard Breipohl

Wolfgang Holla

Heiner Jendralla

Gerhard Beck

Original Assignee

Aventis Pharma Deutschland 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.)

2000-01-28

Filing date

2001-01-18

Publication date

2003-04-01

2001-01-18 Application filed by Aventis Pharma Deutschland Gmbh filed Critical Aventis Pharma Deutschland Gmbh

2003-04-01 Publication of SK10842002A3 publication Critical patent/SK10842002A3/sk

Links

238000000034 method Methods 0.000 title claims abstract description 78
238000002360 preparation method Methods 0.000 title claims abstract description 28
239000000543 intermediate Substances 0.000 title abstract description 12
150000003839 salts Chemical class 0.000 claims abstract description 76
238000006243 chemical reaction Methods 0.000 claims abstract description 50
150000001450 anions Chemical class 0.000 claims abstract description 41
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 13
150000001875 compounds Chemical class 0.000 claims description 194
238000005984 hydrogenation reaction Methods 0.000 claims description 46
239000002253 acid Substances 0.000 claims description 35
239000003054 catalyst Substances 0.000 claims description 30
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 24
KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 22
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 11
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 11
229960003237 betaine Drugs 0.000 claims description 11
238000007327 hydrogenolysis reaction Methods 0.000 claims description 10
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 9
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 claims description 9
101150096839 Fcmr gene Proteins 0.000 claims description 6
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HJBLUNHMOKFZQX-UHFFFAOYSA-N 3-hydroxy-1,2,3-benzotriazin-4-one Chemical compound C1=CC=C2C(=O)N(O)N=NC2=C1 HJBLUNHMOKFZQX-UHFFFAOYSA-N 0.000 claims description 5
238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 5
MHMNQHQEAPWCEF-CEXZUDLPSA-N [Rh+].C([C@H]1C[C@H](CN1C(=O)OC(C)(C)C)P(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)C1=CC=CC=C1 Chemical compound [Rh+].C([C@H]1C[C@H](CN1C(=O)OC(C)(C)C)P(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)C1=CC=CC=C1 MHMNQHQEAPWCEF-CEXZUDLPSA-N 0.000 claims 1
239000007858 starting material Substances 0.000 abstract description 15
150000001409 amidines Chemical class 0.000 abstract description 10
238000009876 asymmetric hydrogenation reaction Methods 0.000 abstract description 9
208000007536 Thrombosis Diseases 0.000 abstract description 6
238000010168 coupling process Methods 0.000 abstract description 4
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PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 abstract description 2
VZTWJWFMCMTPJP-UHFFFAOYSA-N 2-[[2-acetamido-3-(4-cyanophenyl)prop-2-enoyl]amino]-2-cyclohexylacetic acid Chemical compound C1CCCCC1C(C(O)=O)NC(=O)C(NC(=O)C)=CC1=CC=C(C#N)C=C1 VZTWJWFMCMTPJP-UHFFFAOYSA-N 0.000 abstract description 2
DVLNTYJJQFFQGW-UHFFFAOYSA-N 2-[[2-acetamido-3-[4-[amino(azaniumylidene)methyl]phenyl]propanoyl]amino]-2-cyclohexylacetate Chemical compound C1CCCCC1C(C(O)=O)NC(=O)C(NC(=O)C)CC1=CC=C(C(N)=N)C=C1 DVLNTYJJQFFQGW-UHFFFAOYSA-N 0.000 abstract description 2
XVWHDXISTYTFDL-UHFFFAOYSA-O 2-amino-3-(1-methylpyridin-1-ium-3-yl)propanamide Chemical class C[N+]1=CC=CC(CC(N)C(N)=O)=C1 XVWHDXISTYTFDL-UHFFFAOYSA-O 0.000 abstract description 2
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101000655609 Streptomyces azureus Thiostrepton Proteins 0.000 abstract description 2
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238000003756 stirring Methods 0.000 description 45
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IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 42
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239000000243 solution Substances 0.000 description 35
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VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 6
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239000002638 heterogeneous catalyst Substances 0.000 description 1
WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 1
229940006607 hirudin Drugs 0.000 description 1
229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
ILVUABTVETXVMV-UHFFFAOYSA-N hydron;bromide;iodide Chemical class Br.I ILVUABTVETXVMV-UHFFFAOYSA-N 0.000 description 1
WCYJQVALWQMJGE-UHFFFAOYSA-M hydroxylammonium chloride Chemical compound [Cl-].O[NH3+] WCYJQVALWQMJGE-UHFFFAOYSA-M 0.000 description 1
VGYYSIDKAKXZEE-UHFFFAOYSA-L hydroxylammonium sulfate Chemical compound O[NH3+].O[NH3+].[O-]S([O-])(=O)=O VGYYSIDKAKXZEE-UHFFFAOYSA-L 0.000 description 1
229910000378 hydroxylammonium sulfate Inorganic materials 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
238000004255 ion exchange chromatography Methods 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
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000011031 large-scale manufacturing process Methods 0.000 description 1
230000007774 longterm Effects 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
238000006140 methanolysis reaction Methods 0.000 description 1
229940102396 methyl bromide Drugs 0.000 description 1
125000004492 methyl ester group Chemical group 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 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
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000010899 nucleation Methods 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
238000005191 phase separation Methods 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
150000003112 potassium compounds Chemical class 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
238000010926 purge Methods 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
239000010453 quartz Substances 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
229910052707 ruthenium Inorganic materials 0.000 description 1
YAYGSLOSTXKUBW-UHFFFAOYSA-N ruthenium(2+) Chemical compound [Ru+2] YAYGSLOSTXKUBW-UHFFFAOYSA-N 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
JVZXXHPGADCTTB-UHFFFAOYSA-M sodium;acetyl acetate;acetate Chemical compound [Na+].CC([O-])=O.CC(=O)OC(C)=O JVZXXHPGADCTTB-UHFFFAOYSA-M 0.000 description 1
238000010532 solid phase synthesis reaction Methods 0.000 description 1
239000012453 solvate Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[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
238000002560 therapeutic procedure Methods 0.000 description 1
239000003868 thrombin inhibitor Substances 0.000 description 1
230000009424 thromboembolic effect Effects 0.000 description 1
CMQCNTNASCDNGR-UHFFFAOYSA-N toluene;hydrate Chemical compound O.CC1=CC=CC=C1 CMQCNTNASCDNGR-UHFFFAOYSA-N 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000027 toxicology Toxicity 0.000 description 1
125000005500 uronium group Chemical group 0.000 description 1
239000003643 water by type Substances 0.000 description 1
238000010626 work up procedure Methods 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
- C07K5/08—Tripeptides
- 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
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Hematology (AREA)
Public Health (AREA)
Diabetes (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Peptides Or Proteins (AREA)
Pyridine Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Catalysts (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Investigating Or Analysing Biological Materials (AREA)

SK1084-2002A 2000-01-28 2001-01-18 Spôsob prípravy acetyl-amidiniofenylalanyl-cyklohexylglycyl- pyridinioalanínamidov a medziprodukty používané pri tomto spôsobe SK10842002A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE10003586		2000-01-28
PCT/EP2001/000523 WO2001055175A2 (en)	2000-01-28	2001-01-18	Process for the preparation of acetyl-amidiniophenylalanyl-cyclohexylglycyl-pyridinioalaninamides

Publications (1)

Publication Number	Publication Date
SK10842002A3 true SK10842002A3 (sk)	2003-04-01

Family

ID=7628946

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1084-2002A SK10842002A3 (sk)	2000-01-28	2001-01-18	Spôsob prípravy acetyl-amidiniofenylalanyl-cyklohexylglycyl- pyridinioalanínamidov a medziprodukty používané pri tomto spôsobe

Country Status (29)

Country	Link
US (2)	US20010031858A1 (cs)
EP (1)	EP1254159B9 (cs)
JP (1)	JP4778181B2 (cs)
KR (1)	KR100758141B1 (cs)
CN (1)	CN1176104C (cs)
AR (1)	AR027246A1 (cs)
AT (1)	ATE325810T1 (cs)
AU (1)	AU779722B2 (cs)
BR (1)	BR0107804A (cs)
CA (1)	CA2398497C (cs)
CZ (1)	CZ20022583A3 (cs)
DE (1)	DE60119491T2 (cs)
DK (1)	DK1254159T3 (cs)
EE (1)	EE200200410A (cs)
ES (1)	ES2262632T3 (cs)
HR (1)	HRP20020631A2 (cs)
HU (1)	HUP0301986A2 (cs)
IL (2)	IL150897A0 (cs)
MX (1)	MXPA02006762A (cs)
NO (1)	NO20023577L (cs)
NZ (1)	NZ520427A (cs)
PL (1)	PL356801A1 (cs)
PT (1)	PT1254159E (cs)
RU (1)	RU2250212C2 (cs)
SK (1)	SK10842002A3 (cs)
TW (1)	TWI236481B (cs)
WO (1)	WO2001055175A2 (cs)
YU (1)	YU51202A (cs)
ZA (1)	ZA200205990B (cs)

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Publication number	Priority date	Publication date	Assignee	Title
CH695999A5 (de)	2002-02-28	2006-11-15	Wilex Ag	Verfahren zur Herstellung von 3- Amidinophenylalanin-Derivaten.
WO2007065691A2 (en) *	2005-12-07	2007-06-14	Technische Universität München	Small peptidic and peptido-mimetic affinity ligands for factor viii and factor viii-like proteins
CN101774942B (zh) *	2010-01-27	2012-08-22	宁波武盛化学有限公司	制备n-乙酰基-dl-环己基甘氨酸的方法
CN102984945B (zh) *	2010-04-20	2014-08-20	凯瑞斯德生化(苏州)有限公司	一种环烯基在β位取代的丙氨酸的不对称合成方法
US9000192B2 (en)	2010-11-29	2015-04-07	Takasago International Corporation	Catalyst for asymmetric hydrogenation and method for manufacturing optically active carbonyl compound using the same
CN115068469B (zh) *	2022-07-08	2024-02-27	深圳市小分子新药创新中心有限公司	Tigit抑制剂及其应用
CN115612702A (zh) *	2022-10-09	2023-01-17	深圳市茵诺圣生物科技有限公司	L-丙氨酸类非天然氨基酸3-(3-吡啶基)-l-丙氨酸的合成方法

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Publication number	Priority date	Publication date	Assignee	Title
DE2916711A1 (de)	1979-04-25	1980-11-06	Behringwerke Ag	Blutgerinnungsfaktoren und verfahren zu ihrer herstellung
US4623717A (en)	1980-03-05	1986-11-18	Miles Laboratories, Inc.	Pasteurized therapeutically active protein compositions
US4440679A (en)	1980-03-05	1984-04-03	Cutter Laboratories, Inc.	Pasteurized therapeutically active protein compositions
SE9301916D0 (sv) *	1993-06-03	1993-06-03	Ab Astra	New peptides derivatives
SK47796A3 (en) *	1993-10-15	1997-03-05	Rhone Poulenc Rorer Pharma	Antithrombotic azacycloalkylalkanoyl peptides and pseudopeptides
US5849510A (en)	1994-04-26	1998-12-15	Selectide Corporation	Factor Xa inhibitors
HUT76346A (en) *	1994-04-26	1997-08-28	Selectide Corp	Factor xa inhibitors
UA48993C2 (uk) *	1995-12-20	2002-09-16	Авентіс Фармасьютікалз, Інк	СПОСІБ ОТРИМАННЯ N-АЦЕТИЛ-(L)-4-ЦІАНОФЕНІЛАЛАНІНУ Аc-(L)-Phe(4-CN)-OH І N-АЦЕТИЛ-(L)-П-АМІДИНФЕНІЛАЛАНІН-ЦИКЛОГЕКСИЛГЛІЦИН-<font face="Symbol">b</font>-(3-N-МЕТИЛПІРИДИН)-АЛАНІНУ Аc-(L)-pАph-Сhg-PalMe(3)-NH<sub>2</sub>
DE19856443A1 (de)	1998-12-08	2000-06-21	Centeon Pharma Gmbh	Stabilisiertes Antithrombin III-Präparat

2001
- 2001-01-18 PT PT01911497T patent/PT1254159E/pt unknown
- 2001-01-18 AR ARP010100225A patent/AR027246A1/es unknown
- 2001-01-18 RU RU2002123046/04A patent/RU2250212C2/ru not_active IP Right Cessation
- 2001-01-18 EE EEP200200410A patent/EE200200410A/xx unknown
- 2001-01-18 AU AU40516/01A patent/AU779722B2/en not_active Ceased
- 2001-01-18 PL PL01356801A patent/PL356801A1/xx unknown
- 2001-01-18 EP EP01911497A patent/EP1254159B9/en not_active Expired - Lifetime
- 2001-01-18 KR KR1020027009583A patent/KR100758141B1/ko not_active Expired - Fee Related
- 2001-01-18 CZ CZ20022583A patent/CZ20022583A3/cs unknown
- 2001-01-18 YU YU51202A patent/YU51202A/sh unknown
- 2001-01-18 SK SK1084-2002A patent/SK10842002A3/sk unknown
- 2001-01-18 JP JP2001561027A patent/JP4778181B2/ja not_active Expired - Fee Related
- 2001-01-18 HR HRP20020631 patent/HRP20020631A2/hr not_active Application Discontinuation
- 2001-01-18 DK DK01911497T patent/DK1254159T3/da active
- 2001-01-18 ES ES01911497T patent/ES2262632T3/es not_active Expired - Lifetime
- 2001-01-18 AT AT01911497T patent/ATE325810T1/de active
- 2001-01-18 HU HU0301986A patent/HUP0301986A2/hu unknown
- 2001-01-18 MX MXPA02006762A patent/MXPA02006762A/es active IP Right Grant
- 2001-01-18 CN CNB018041523A patent/CN1176104C/zh not_active Expired - Fee Related
- 2001-01-18 CA CA2398497A patent/CA2398497C/en not_active Expired - Fee Related
- 2001-01-18 NZ NZ520427A patent/NZ520427A/en unknown
- 2001-01-18 WO PCT/EP2001/000523 patent/WO2001055175A2/en not_active Ceased
- 2001-01-18 IL IL15089701A patent/IL150897A0/xx active IP Right Grant
- 2001-01-18 BR BR0107804-6A patent/BR0107804A/pt not_active Application Discontinuation
- 2001-01-18 DE DE60119491T patent/DE60119491T2/de not_active Expired - Lifetime
- 2001-01-26 US US09/769,487 patent/US20010031858A1/en not_active Abandoned
- 2001-03-07 TW TW090101207A patent/TWI236481B/zh not_active IP Right Cessation
2002
- 2002-07-24 IL IL150897A patent/IL150897A/en not_active IP Right Cessation
- 2002-07-26 ZA ZA200205990A patent/ZA200205990B/en unknown
- 2002-07-26 NO NO20023577A patent/NO20023577L/no unknown
2004
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Also Published As

Publication number	Publication date
AU779722B2 (en)	2005-02-10
HUP0301986A2 (hu)	2003-09-29
CZ20022583A3 (cs)	2002-10-16
ES2262632T3 (es)	2006-12-01
JP4778181B2 (ja)	2011-09-21
DK1254159T3 (da)	2006-09-11
DE60119491D1 (de)	2006-06-14
EP1254159A2 (en)	2002-11-06
RU2002123046A (ru)	2004-01-10
PT1254159E (pt)	2006-07-31
DE60119491T2 (de)	2006-11-16
CA2398497A1 (en)	2001-08-02
IL150897A (en)	2008-08-07
WO2001055175A3 (en)	2002-02-21
TWI236481B (en)	2005-07-21
AU4051601A (en)	2001-08-07
EP1254159B9 (en)	2006-06-28
NO20023577D0 (no)	2002-07-26
EE200200410A (et)	2003-12-15
AR027246A1 (es)	2003-03-19
US20010031858A1 (en)	2001-10-18
NZ520427A (en)	2004-02-27
RU2250212C2 (ru)	2005-04-20
HRP20020631A2 (en)	2004-12-31
CA2398497C (en)	2011-04-26
WO2001055175A2 (en)	2001-08-02
MXPA02006762A (es)	2002-10-23
NO20023577L (no)	2002-08-28
YU51202A (sh)	2005-11-28
KR20030019306A (ko)	2003-03-06
BR0107804A (pt)	2002-10-22
CN1176104C (zh)	2004-11-17
CN1396928A (zh)	2003-02-12
JP2003523364A (ja)	2003-08-05
IL150897A0 (en)	2003-02-12
PL356801A1 (en)	2004-07-12
US7084250B2 (en)	2006-08-01
HK1051866A1 (en)	2003-08-22
KR100758141B1 (ko)	2007-09-13
ZA200205990B (en)	2003-04-30
ATE325810T1 (de)	2006-06-15
EP1254159B1 (en)	2006-05-10
US20040225109A1 (en)	2004-11-11

Publication	Publication Date	Title
KR960004900B1 (ko)	1996-04-17	디아민의 선택적 아미딘화 방법
CA3098707A1 (en)	2019-12-05	Method for solution-phase peptide synthesis and protecting strategies thereof
EP1254159B1 (en)	2006-05-10	Process for the preparation of acetyl-amidiniophenylalanyl-cyclohexylglycyl-pyridylalaninamides
Shue et al.	1991	Novel methodology for the synthesis of trans-alkene dipeptide isosteres
JP4044614B2 (ja)	2008-02-06	Ｎ―アセチル―（Ｌ）―４―シアノフェニルアラニンＡｃ―（Ｌ）―Ｐｈｅ（４―ＣＮ）―ＯＨおよびＮ―アセチル―（Ｌ）―ｐ―アミジノフェニルアラニン―シクロヘキシルグリシン―β―（３―Ｎ―メチルピリジニウム）―アラニンＡｃ―（Ｌ）―ｐＡｐｈ―Ｃｈｇ―ＰａｌＭｅ（３）―ＮＨ２の新規な製法
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NZ523217A (en)	2004-07-30	Chemical process
HK1051866B (en)	2005-05-06	Process for the preparation of acetyl-amidiniophenylalanyl-cyclohexylglycyl-pyridinioalaninamides
KR20160081864A (ko)	2016-07-08	티올기를 갖는 d-체 또는 l-체 아미노산 유도체의 제조 방법
CN101861299A (zh)	2010-10-13	氨基酸衍生物的立体选择性制备方法
US20080234493A1 (en)	2008-09-25	Process for the Preparation of 2-[N-[{S)-1-Ethoxycarbonyl-3-Phenylpropyl]-(S)-Alanyl]-(1S,3S,5S)-2-Azabicyclo[3.3.0]Oct- an-3-Carboxylic Acid
JPH1143475A (ja)	1999-02-16	光学活性Ｎ−カルボベンゾキシ−ｔｅｒｔ−ロイシンの製造法
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