FI63018C - Foerfarande foer framstaellning av terapeutiskt verkande tyrosinderivat - Google Patents
Foerfarande foer framstaellning av terapeutiskt verkande tyrosinderivat Download PDFInfo
- Publication number
- FI63018C FI63018C FI753577A FI753577A FI63018C FI 63018 C FI63018 C FI 63018C FI 753577 A FI753577 A FI 753577A FI 753577 A FI753577 A FI 753577A FI 63018 C FI63018 C FI 63018C
- Authority
- FI
- Finland
- Prior art keywords
- compound
- formula
- formulation
- cox
- acid
- Prior art date
Links
- 230000001225 therapeutic effect Effects 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 49
- 239000000203 mixture Substances 0.000 claims description 23
- -1 carbonyl halide Chemical class 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 150000003667 tyrosine derivatives Chemical class 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 150000001340 alkali metals Chemical class 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
- 229910052749 magnesium Inorganic materials 0.000 claims description 3
- 239000011777 magnesium Substances 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 229910052782 aluminium Inorganic materials 0.000 claims description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 7
- 125000004018 acid anhydride group Chemical group 0.000 claims 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims 1
- 150000001342 alkaline earth metals Chemical class 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 229940085942 formulation r Drugs 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 206010052428 Wound Diseases 0.000 description 12
- 208000027418 Wounds and injury Diseases 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 241000700159 Rattus Species 0.000 description 10
- 208000007107 Stomach Ulcer Diseases 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- MPQGZNHUHOCREQ-GOTSBHOMSA-N (2s)-3-(4-hydroxyphenyl)-2-[[(2s)-2-[(4-methoxybenzoyl)amino]-3-phenylpropanoyl]amino]propanoic acid Chemical compound C1=CC(OC)=CC=C1C(=O)N[C@H](C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)CC1=CC=CC=C1 MPQGZNHUHOCREQ-GOTSBHOMSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 201000005917 gastric ulcer Diseases 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- ZPACYDRSPFRDHO-ROBAGEODSA-N Gefarnate Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CCC(=O)OC\C=C(/C)CCC=C(C)C ZPACYDRSPFRDHO-ROBAGEODSA-N 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 229960003779 gefarnate Drugs 0.000 description 5
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229920001386 Gefarnate Polymers 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
- JFHFHARVQYOQAJ-VXKWHMMOSA-N (2s)-2-[[(2s)-2-benzamido-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)C=1C=CC=CC=1)C1=CC=C(O)C=C1 JFHFHARVQYOQAJ-VXKWHMMOSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-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
- FSXRLASFHBWESK-HOTGVXAUSA-N Phe-Tyr Chemical class C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 FSXRLASFHBWESK-HOTGVXAUSA-N 0.000 description 3
- 150000008065 acid anhydrides Chemical group 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- JRRNMWUHYNAHFR-ZEQRLZLVSA-N methyl (2s)-3-(4-hydroxyphenyl)-2-[[(2s)-2-[(4-methoxybenzoyl)amino]-3-phenylpropanoyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)C=1C=CC(OC)=CC=1)C1=CC=C(O)C=C1 JRRNMWUHYNAHFR-ZEQRLZLVSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- BHFKERBWGWXNFK-HNNXBMFYSA-N (2s)-2-[(4-methoxybenzoyl)amino]-3-phenylpropanoic acid Chemical compound C1=CC(OC)=CC=C1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 BHFKERBWGWXNFK-HNNXBMFYSA-N 0.000 description 2
- LIDVIUGMMFTRSD-FVGYRXGTSA-N (2s)-3-(4-hydroxyphenyl)-2-(methylamino)propanoic acid;hydrochloride Chemical compound Cl.CN[C@H](C(O)=O)CC1=CC=C(O)C=C1 LIDVIUGMMFTRSD-FVGYRXGTSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 210000000683 abdominal cavity Anatomy 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- FSXRLASFHBWESK-UHFFFAOYSA-N dipeptide phenylalanyl-tyrosine Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FSXRLASFHBWESK-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- VAOTVDABLTUNEK-GOTSBHOMSA-N methyl (2s)-2-[[(2s)-2-benzamido-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)C=1C=CC=CC=1)C1=CC=C(O)C=C1 VAOTVDABLTUNEK-GOTSBHOMSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- VIXIDUNQMRFCFO-UHFFFAOYSA-N 3-(ethyliminomethylideneamino)-n-methylpropan-1-amine Chemical compound CCN=C=NCCCNC VIXIDUNQMRFCFO-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- AXDLCFOOGCNDST-VIFPVBQESA-M Methyltyrosinate Chemical compound CN[C@H](C([O-])=O)CC1=CC=C(O)C=C1 AXDLCFOOGCNDST-VIFPVBQESA-M 0.000 description 1
- NPKISZUVEBESJI-AWEZNQCLSA-N N-benzoyl-L-phenylalanine Chemical compound C([C@@H](C(=O)O)NC(=O)C=1C=CC=CC=1)C1=CC=CC=C1 NPKISZUVEBESJI-AWEZNQCLSA-N 0.000 description 1
- NPKISZUVEBESJI-UHFFFAOYSA-N Nalpha-benzoyl-L-phenylalanine Natural products C=1C=CC=CC=1C(=O)NC(C(=O)O)CC1=CC=CC=C1 NPKISZUVEBESJI-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical group 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 230000009982 effect on human Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- RABGWIHVAJQKMC-QJHJCNPRSA-N methyl (2s)-2-[[(2s)-2-amino-3-phenylpropanoyl]amino]-3-(4-hydroxyphenyl)propanoate;hydrochloride Chemical compound Cl.C([C@@H](C(=O)OC)NC(=O)[C@@H](N)CC=1C=CC=CC=1)C1=CC=C(O)C=C1 RABGWIHVAJQKMC-QJHJCNPRSA-N 0.000 description 1
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000001953 recrystallisation Methods 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
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- JAMJRFYHSSLQEW-SJEIDVEUSA-M sodium;(2s)-3-(4-hydroxyphenyl)-2-[[(2s)-2-[(4-methoxybenzoyl)amino]-3-phenylpropanoyl]amino]propanoate Chemical compound [Na+].C1=CC(OC)=CC=C1C(=O)N[C@H](C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C([O-])=O)CC1=CC=CC=C1 JAMJRFYHSSLQEW-SJEIDVEUSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1027—Tetrapeptides containing heteroatoms different from O, S, or N
-
- 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
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- 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
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
-
- 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
- C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Life Sciences & Earth Sciences (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP14513474A JPS51125241A (en) | 1974-12-18 | 1974-12-18 | Process for preparing tyrosinol derivatives |
| JP14513374A JPS51125240A (en) | 1974-12-18 | 1974-12-18 | Process for preparing tyrosinos derivatives |
| JP14513374 | 1974-12-18 | ||
| JP14513474 | 1974-12-18 | ||
| JP50039959A JPS5810379B2 (ja) | 1975-04-02 | 1975-04-02 | ジペプチドルイノセイホウ |
| JP3995975 | 1975-04-02 | ||
| JP4100075 | 1975-04-04 | ||
| JP50041000A JPS5811425B2 (ja) | 1975-04-04 | 1975-04-04 | ジペプチドルイノセイゾウホウ |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI753577A7 FI753577A7 (Direct) | 1976-06-19 |
| FI63018B FI63018B (fi) | 1982-12-31 |
| FI63018C true FI63018C (fi) | 1983-04-11 |
Family
ID=27460840
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI753577A FI63018C (fi) | 1974-12-18 | 1975-12-18 | Foerfarande foer framstaellning av terapeutiskt verkande tyrosinderivat |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US4025644A (Direct) |
| DE (1) | DE2557145C3 (Direct) |
| DK (1) | DK571775A (Direct) |
| FI (1) | FI63018C (Direct) |
| FR (1) | FR2294694A1 (Direct) |
| NL (1) | NL171577B (Direct) |
| PH (1) | PH12663A (Direct) |
| SE (1) | SE410596B (Direct) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| LU78804A1 (de) * | 1977-12-30 | 1979-07-20 | Byk Gulden Lomberg Chem Fab | N-substituierte w-aminoalkanoyl-w-aminoalkansaeuren,ihre verwendung und verfahren zu ihrer herstellung sowie diese verbindungen enthaltende arzneimittel |
| FR2480747A1 (fr) * | 1980-04-17 | 1981-10-23 | Roques Bernard | Derives d'acides amines et leur application therapeutique |
| AU584502B2 (en) * | 1987-03-30 | 1989-05-25 | Shosuke Okamoto | Phenylalanine derivatives and proteinase inhibitor |
| JP2578044B2 (ja) * | 1992-03-14 | 1997-02-05 | 呉羽化学工業株式会社 | フェニルアラニン−グリシン誘導体、その製造方法、及びその誘導体を含有する抗腫瘍剤 |
| WO1995012611A1 (en) * | 1993-11-01 | 1995-05-11 | Japat Ltd. | Endothelin receptor antagonists |
| WO2000027800A1 (en) * | 1998-11-09 | 2000-05-18 | Smithkline Beecham Corporation | Ccr-3 receptor antagonists |
| CN100480234C (zh) * | 2006-10-20 | 2009-04-22 | 贵州省中国科学院天然产物化学重点实验室 | N-(n-苯甲酰基-苯丙氨酰基)-苯丙氨酸二肽衍生物及其制备方法和用途 |
| US9023809B2 (en) * | 2008-03-27 | 2015-05-05 | The Key Laboratory Of Chemistry For Natural Products Of Guizhou Province And Chinese Academy Of Sciences | Phenylalanine dipeptide derivatives, compositions and use thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1158493B (de) * | 1961-07-11 | 1963-12-05 | Troponwerke Dinklage & Co | Verfahren zur Herstellung von substituierten N-(Phenylaethyl)-carbaminsaeureestern |
| CH552567A (de) * | 1970-10-30 | 1974-08-15 | Hoffmann La Roche | Verfahren zur herstellung von phenylalaninderivaten. |
| US3843796A (en) * | 1971-04-26 | 1974-10-22 | Merck & Co Inc | Antihypertensive agents |
-
1975
- 1975-12-09 US US05/639,117 patent/US4025644A/en not_active Expired - Lifetime
- 1975-12-16 DK DK571775A patent/DK571775A/da unknown
- 1975-12-17 SE SE7514308A patent/SE410596B/xx unknown
- 1975-12-18 NL NLAANVRAGE7514765,A patent/NL171577B/xx not_active IP Right Cessation
- 1975-12-18 FI FI753577A patent/FI63018C/fi not_active IP Right Cessation
- 1975-12-18 DE DE2557145A patent/DE2557145C3/de not_active Expired
- 1975-12-18 FR FR7538895A patent/FR2294694A1/fr active Granted
- 1975-12-18 PH PH17889A patent/PH12663A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SE410596B (sv) | 1979-10-22 |
| DE2557145B2 (de) | 1979-02-08 |
| DK571775A (da) | 1976-06-19 |
| SE7514308L (sv) | 1976-06-21 |
| DE2557145A1 (de) | 1976-06-24 |
| NL171577B (nl) | 1982-11-16 |
| FR2294694B1 (Direct) | 1978-07-28 |
| FI63018B (fi) | 1982-12-31 |
| PH12663A (en) | 1979-07-11 |
| US4025644A (en) | 1977-05-24 |
| FI753577A7 (Direct) | 1976-06-19 |
| FR2294694A1 (fr) | 1976-07-16 |
| DE2557145C3 (de) | 1979-10-04 |
| NL7514765A (nl) | 1976-06-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: DAIICHI SEIYAKU CO. LTD. |