JPS6325579B2 - - Google Patents
Info
- Publication number
- JPS6325579B2 JPS6325579B2 JP55091690A JP9169080A JPS6325579B2 JP S6325579 B2 JPS6325579 B2 JP S6325579B2 JP 55091690 A JP55091690 A JP 55091690A JP 9169080 A JP9169080 A JP 9169080A JP S6325579 B2 JPS6325579 B2 JP S6325579B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- amino
- formula
- hydroxy
- configuration
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
Links
- 239000000126 substance Substances 0.000 claims description 10
- 238000007796 conventional method Methods 0.000 claims description 7
- VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-MCIONIFRSA-N 0.000 claims description 6
- VGGGPCQERPFHOB-UHFFFAOYSA-N Bestatin Natural products CC(C)CC(C(O)=O)NC(=O)C(O)C(N)CC1=CC=CC=C1 VGGGPCQERPFHOB-UHFFFAOYSA-N 0.000 claims description 6
- 229950009811 ubenimex Drugs 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 10
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- 238000004949 mass spectrometry Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 150000002148 esters Chemical group 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- -1 N-tert-butoxycarbonylamino group Chemical group 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 102100032126 Aminopeptidase B Human genes 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 108090000449 aminopeptidase B Proteins 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 108010016626 Dipeptides Proteins 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 241001494479 Pecora Species 0.000 description 3
- 150000001413 amino acids Chemical class 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
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000001766 physiological effect Effects 0.000 description 3
- 108090000915 Aminopeptidases Proteins 0.000 description 2
- 102000004400 Aminopeptidases Human genes 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000002900 effect on cell Effects 0.000 description 2
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 230000003308 immunostimulating effect Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 230000005951 type IV hypersensitivity Effects 0.000 description 2
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 2
- YXQDBEZPBMCYAI-NXEZZACHSA-N (2s,3r)-3-amino-4-phenylbutane-1,2-diol Chemical compound OC[C@@H](O)[C@H](N)CC1=CC=CC=C1 YXQDBEZPBMCYAI-NXEZZACHSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-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
- 101100005765 Arabidopsis thaliana CDF1 gene Proteins 0.000 description 1
- 101100007579 Arabidopsis thaliana CPP1 gene Proteins 0.000 description 1
- DICSXQHGGOAUNU-AWEZNQCLSA-N L-arginine 2-naphthylamide Chemical compound C1=CC=CC2=CC(NC(=O)[C@H](CCCN=C(N)N)N)=CC=C21 DICSXQHGGOAUNU-AWEZNQCLSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 230000000397 acetylating effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- MBRRYUQWSOODEO-LBPRGKRZSA-N benzyl (2s)-2-amino-4-methylpentanoate Chemical compound CC(C)C[C@H](N)C(=O)OCC1=CC=CC=C1 MBRRYUQWSOODEO-LBPRGKRZSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- KPUNOVLMCQQCSK-UHFFFAOYSA-N diazomethane;ethoxyethane Chemical compound C=[N+]=[N-].CCOCC KPUNOVLMCQQCSK-UHFFFAOYSA-N 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- OBKXEAXTFZPCHS-UHFFFAOYSA-N gamma-phenylbutyric acid Natural products OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 1
- 239000002223 garnet Substances 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- GHQOYCIIRQVAEN-UHFFFAOYSA-N methyl 2-amino-2-hydroxy-4-phenylbutanoate Chemical compound COC(=O)C(N)(O)CCC1=CC=CC=C1 GHQOYCIIRQVAEN-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000006215 rectal suppository Substances 0.000 description 1
- 229940100618 rectal suppository Drugs 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9169080A JPS5716842A (en) | 1980-07-07 | 1980-07-07 | Substance related to bestatin and its preparation |
| US06/272,211 US4370318A (en) | 1980-07-07 | 1981-06-10 | Bestatin-related compounds as immunopotentiator |
| GB8119397A GB2083046B (en) | 1980-07-07 | 1981-06-24 | Bestatin-related compounds |
| DE3153030A DE3153030C2 (de) | 1980-07-07 | 1981-07-06 | Verwendung von (2S,3R)-3-Amino-2-hydroxy-4-phenylbutansäureverbindungen als Immunverstärkungsmittel |
| DE3126606A DE3126606C2 (de) | 1980-07-07 | 1981-07-06 | (2S,3R)-3-Amino-2-hydroxy-4-phenylbutansäure-amide und -peptide sowie diese enthaltende Arzneimittel |
| IT09465/81A IT1167937B (it) | 1980-07-07 | 1981-07-06 | Composti collegati alla bestatina come immunopotenziatore |
| CA000381174A CA1178610A (en) | 1980-07-07 | 1981-07-06 | Bestatin-related compounds as immunopotentiator |
| IT1981A09465A IT8109465A1 (it) | 1980-07-07 | 1981-07-06 | Composti collegati alla bestatina come immunopotenziatore |
| FR8113332A FR2485924A1 (fr) | 1980-07-07 | 1981-07-07 | Nouvelles compositions pharmaceutiques immunopotentialisatrices, et nouveaux composes apparentes a la bestatine entrant dans ces compositions |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9169080A JPS5716842A (en) | 1980-07-07 | 1980-07-07 | Substance related to bestatin and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5716842A JPS5716842A (en) | 1982-01-28 |
| JPS6325579B2 true JPS6325579B2 (US06174465-20010116-C00003.png) | 1988-05-26 |
Family
ID=14033494
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9169080A Granted JPS5716842A (en) | 1980-07-07 | 1980-07-07 | Substance related to bestatin and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5716842A (US06174465-20010116-C00003.png) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63300064A (ja) * | 1987-05-29 | 1988-12-07 | Tokinori Kudo | シ−ト収容装置 |
| JPH0229774U (US06174465-20010116-C00003.png) * | 1988-08-12 | 1990-02-26 |
-
1980
- 1980-07-07 JP JP9169080A patent/JPS5716842A/ja active Granted
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63300064A (ja) * | 1987-05-29 | 1988-12-07 | Tokinori Kudo | シ−ト収容装置 |
| JPH0229774U (US06174465-20010116-C00003.png) * | 1988-08-12 | 1990-02-26 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5716842A (en) | 1982-01-28 |
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