HU196833B - Process for producing peptide derivatives comprising statine or its derivatives - Google Patents
Process for producing peptide derivatives comprising statine or its derivatives Download PDFInfo
- Publication number
- HU196833B HU196833B HU85911A HU91185A HU196833B HU 196833 B HU196833 B HU 196833B HU 85911 A HU85911 A HU 85911A HU 91185 A HU91185 A HU 91185A HU 196833 B HU196833 B HU 196833B
- Authority
- HU
- Hungary
- Prior art keywords
- mmol
- phenylalanine
- statin
- butyloxycarbonyl
- histidine
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 20
- 238000000034 method Methods 0.000 title claims description 13
- DFVFTMTWCUHJBL-BQBZGAKWSA-N statine Chemical compound CC(C)C[C@H](N)[C@@H](O)CC(O)=O DFVFTMTWCUHJBL-BQBZGAKWSA-N 0.000 title 1
- -1 1,2,3,4-tetrahydroquinolin-1-yl Chemical group 0.000 claims abstract description 125
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 6
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 63
- 150000001875 compounds Chemical class 0.000 claims description 39
- 229960005190 phenylalanine Drugs 0.000 claims description 38
- 229960002885 histidine Drugs 0.000 claims description 30
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 27
- 239000004472 Lysine Substances 0.000 claims description 27
- 238000002360 preparation method Methods 0.000 claims description 26
- 229960000310 isoleucine Drugs 0.000 claims description 17
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 13
- 229960002989 glutamic acid Drugs 0.000 claims description 11
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 235000019766 L-Lysine Nutrition 0.000 claims description 4
- CYZKJBZEIFWZSR-LURJTMIESA-N N(alpha)-methyl-L-histidine Chemical compound CN[C@H](C(O)=O)CC1=CNC=N1 CYZKJBZEIFWZSR-LURJTMIESA-N 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 229930182844 L-isoleucine Natural products 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229960002429 proline Drugs 0.000 claims description 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- QDGAVODICPCDMU-UHFFFAOYSA-N 2-amino-3-[3-[bis(2-chloroethyl)amino]phenyl]propanoic acid Chemical group OC(=O)C(N)CC1=CC=CC(N(CCCl)CCCl)=C1 QDGAVODICPCDMU-UHFFFAOYSA-N 0.000 claims description 2
- 229930182821 L-proline Natural products 0.000 claims description 2
- SORARJZLMNRBAQ-UHFFFAOYSA-N n,n',n'-trimethylpropane-1,3-diamine Chemical compound CNCCCN(C)C SORARJZLMNRBAQ-UHFFFAOYSA-N 0.000 claims description 2
- ALBODLTZUXKBGZ-JUUVMNCLSA-N (2s)-2-amino-3-phenylpropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CC1=CC=CC=C1 ALBODLTZUXKBGZ-JUUVMNCLSA-N 0.000 claims 1
- DVEQYBXCFNPUGR-UHFFFAOYSA-N 4-amino-5-methylheptanoic acid Chemical compound CCC(C)C(N)CCC(O)=O DVEQYBXCFNPUGR-UHFFFAOYSA-N 0.000 claims 1
- KTNSTFKQBHAPEU-FHAQVOQBSA-N NCCCC(O)=O.CC[C@H](C)[C@H](N)C(O)=O Chemical compound NCCCC(O)=O.CC[C@H](C)[C@H](N)C(O)=O KTNSTFKQBHAPEU-FHAQVOQBSA-N 0.000 claims 1
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- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 21
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- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 5
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- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate 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
- 238000001819 mass spectrum Methods 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- HQEIPVHJHZTMDP-JEDNCBNOSA-N methyl (2s)-pyrrolidine-2-carboxylate;hydrochloride Chemical compound Cl.COC(=O)[C@@H]1CCCN1 HQEIPVHJHZTMDP-JEDNCBNOSA-N 0.000 description 1
- YXMMTUJDQTVJEN-WDSKDSINSA-N methyl (2s,3s)-2-amino-3-methylpentanoate Chemical compound CC[C@H](C)[C@H](N)C(=O)OC YXMMTUJDQTVJEN-WDSKDSINSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- FVQRVDZXHMKZCP-UHFFFAOYSA-N n,n',n'-trimethylpropane-1,3-diamine;dihydrochloride Chemical compound Cl.Cl.CNCCCN(C)C FVQRVDZXHMKZCP-UHFFFAOYSA-N 0.000 description 1
- BEGYNHNEBDHIEG-UHFFFAOYSA-N n-ethyl-n'-(1-morpholin-4-ylcyclohexyl)methanediimine Chemical compound C1COCCN1C1(N=C=NCC)CCCCC1 BEGYNHNEBDHIEG-UHFFFAOYSA-N 0.000 description 1
- LMTGCJANOQOGPI-UHFFFAOYSA-N n-methyl-n-phenylacetamide Chemical compound CC(=O)N(C)C1=CC=CC=C1 LMTGCJANOQOGPI-UHFFFAOYSA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 229950000964 pepstatin Drugs 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- NQEDSLMJTARJAI-UHFFFAOYSA-N phenol;2h-triazole Chemical compound C1=CNN=N1.OC1=CC=CC=C1 NQEDSLMJTARJAI-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- ISHLCKAQWKBMAU-UHFFFAOYSA-N tert-butyl n-diazocarbamate Chemical compound CC(C)(C)OC(=O)N=[N+]=[N-] ISHLCKAQWKBMAU-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 150000008648 triflates Chemical class 0.000 description 1
- IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 238000010792 warming 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
- C07K7/14—Angiotensins: Related peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Vascular Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US58827984A | 1984-03-12 | 1984-03-12 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HUT37442A HUT37442A (en) | 1985-12-28 |
| HU196833B true HU196833B (en) | 1989-01-30 |
Family
ID=24353222
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU85911A HU196833B (en) | 1984-03-12 | 1985-03-12 | Process for producing peptide derivatives comprising statine or its derivatives |
Country Status (13)
| Country | Link |
|---|---|
| KR (1) | KR870000371B1 (da) |
| AT (1) | ATE52519T1 (da) |
| DE (1) | DE3577562D1 (da) |
| ES (1) | ES8606397A1 (da) |
| GR (1) | GR850626B (da) |
| HU (1) | HU196833B (da) |
| IE (1) | IE57862B1 (da) |
| IL (1) | IL74572A (da) |
| NO (1) | NO850975L (da) |
| NZ (1) | NZ211403A (da) |
| PH (1) | PH23769A (da) |
| YU (1) | YU46085A (da) |
| ZA (1) | ZA851832B (da) |
-
1985
- 1985-03-12 KR KR1019850001617A patent/KR870000371B1/ko not_active Expired
- 1985-03-12 IE IE640/85A patent/IE57862B1/en not_active IP Right Cessation
- 1985-03-12 AT AT85301691T patent/ATE52519T1/de not_active IP Right Cessation
- 1985-03-12 NO NO850975A patent/NO850975L/no unknown
- 1985-03-12 GR GR850626A patent/GR850626B/el unknown
- 1985-03-12 NZ NZ211403A patent/NZ211403A/xx unknown
- 1985-03-12 ES ES541194A patent/ES8606397A1/es not_active Expired
- 1985-03-12 DE DE8585301691T patent/DE3577562D1/de not_active Expired - Lifetime
- 1985-03-12 IL IL74572A patent/IL74572A/xx not_active IP Right Cessation
- 1985-03-12 PH PH31980A patent/PH23769A/en unknown
- 1985-03-12 HU HU85911A patent/HU196833B/hu not_active IP Right Cessation
- 1985-03-12 ZA ZA851832A patent/ZA851832B/xx unknown
- 1985-03-21 YU YU00460/85A patent/YU46085A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PH23769A (en) | 1989-11-03 |
| IL74572A0 (en) | 1985-06-30 |
| KR850006940A (ko) | 1985-10-25 |
| NO850975L (no) | 1985-09-13 |
| DE3577562D1 (de) | 1990-06-13 |
| IE57862B1 (en) | 1993-05-05 |
| ES8606397A1 (es) | 1986-04-16 |
| ATE52519T1 (de) | 1990-05-15 |
| IL74572A (en) | 1989-09-28 |
| IE850640L (en) | 1985-09-12 |
| GR850626B (da) | 1985-07-11 |
| ES541194A0 (es) | 1986-04-16 |
| ZA851832B (en) | 1986-10-29 |
| NZ211403A (en) | 1989-01-27 |
| HUT37442A (en) | 1985-12-28 |
| YU46085A (en) | 1988-02-29 |
| KR870000371B1 (ko) | 1987-03-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HU90 | Patent valid on 900628 | ||
| HMM4 | Cancellation of final prot. due to non-payment of fee |