CH630892A5 - Process for preparing bestatin compounds. - Google Patents
Process for preparing bestatin compounds. Download PDFInfo
- Publication number
- CH630892A5 CH630892A5 CH933676A CH933676A CH630892A5 CH 630892 A5 CH630892 A5 CH 630892A5 CH 933676 A CH933676 A CH 933676A CH 933676 A CH933676 A CH 933676A CH 630892 A5 CH630892 A5 CH 630892A5
- Authority
- CH
- Switzerland
- Prior art keywords
- amino
- group
- hydroxy
- ahpa
- leucine
- Prior art date
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- VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical class 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 title claims description 19
- 238000004519 manufacturing process Methods 0.000 title 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 111
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 56
- 238000000034 method Methods 0.000 claims description 37
- -1 benzoyloxycarbonyl group Chemical group 0.000 claims description 33
- 150000001413 amino acids Chemical class 0.000 claims description 21
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-Leucine Natural products CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 claims description 12
- 239000003208 petroleum Substances 0.000 claims description 12
- 125000006239 protecting group Chemical group 0.000 claims description 12
- 125000003277 amino group Chemical group 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 9
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
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- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
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- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000000524 functional group Chemical group 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
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- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-Valine Natural products CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 3
- JVVXZOOGOGPDRZ-SLFFLAALSA-N [(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 JVVXZOOGOGPDRZ-SLFFLAALSA-N 0.000 claims description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
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- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
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- 125000003118 aryl group Chemical group 0.000 claims description 2
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
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- 239000000243 solution Substances 0.000 description 26
- JXJYTERRLRAUSF-CVEARBPZSA-N (2s,3r)-2-hydroxy-4-phenyl-3-(phenylmethoxycarbonylamino)butanoic acid Chemical compound C([C@H]([C@H](O)C(O)=O)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 JXJYTERRLRAUSF-CVEARBPZSA-N 0.000 description 25
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 23
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 19
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- 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 description 16
- 239000000203 mixture Substances 0.000 description 16
- 229950009811 ubenimex Drugs 0.000 description 16
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- 235000001014 amino acid Nutrition 0.000 description 14
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 8
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- JXJYTERRLRAUSF-HZPDHXFCSA-N (2r,3r)-2-hydroxy-4-phenyl-3-(phenylmethoxycarbonylamino)butanoic acid Chemical compound C([C@H]([C@@H](O)C(O)=O)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 JXJYTERRLRAUSF-HZPDHXFCSA-N 0.000 description 5
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- NBLHOLNNKJBEDC-XOGQCRKLSA-N [(2r,3s,4s,5r,6r)-2-[(2r,3s,4s,5s,6s)-2-[(1r,2s)-2-[[6-amino-2-[(1s)-3-amino-1-[[(2s)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[[(2r,3s,4s)-5-[[(2s,3r)-1-[2-[4-[4-[4-(diaminomethylideneamino)butylcarbamoyl]-1,3-th Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCCCN=C(N)N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C NBLHOLNNKJBEDC-XOGQCRKLSA-N 0.000 description 5
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- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- SRRKNRDXURUMPP-UHFFFAOYSA-N sodium disulfide Chemical compound [Na+].[Na+].[S-][S-] SRRKNRDXURUMPP-UHFFFAOYSA-N 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 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
- NPDBDJFLKKQMCM-UHFFFAOYSA-N tert-butylglycine Chemical compound CC(C)(C)C(N)C(O)=O NPDBDJFLKKQMCM-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 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
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229920001567 vinyl ester resin Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH579680A CH634292A5 (en) | 1976-07-21 | 1980-07-29 | Process for preparing bestatin compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB30632/75A GB1510477A (en) | 1975-07-22 | 1975-07-22 | Peptides and to amino acid intermediates thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH630892A5 true CH630892A5 (en) | 1982-07-15 |
Family
ID=10310676
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH933676A CH630892A5 (en) | 1975-07-22 | 1976-07-21 | Process for preparing bestatin compounds. |
Country Status (12)
| Country | Link |
|---|---|
| JP (2) | JPS52136118A (cs) |
| AU (1) | AU506003B2 (cs) |
| CA (1) | CA1104156A (cs) |
| CH (1) | CH630892A5 (cs) |
| CS (2) | CS201034B2 (cs) |
| DE (2) | DE2632396C2 (cs) |
| DK (1) | DK149110C (cs) |
| FR (1) | FR2318863A1 (cs) |
| GB (1) | GB1510477A (cs) |
| HU (1) | HU183048B (cs) |
| NL (1) | NL7608064A (cs) |
| SE (3) | SE431642B (cs) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2725732C2 (de) | 1977-06-07 | 1983-01-05 | Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai, Tokyo | Bestatin-Analoga, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende pharmazeutische Präparate |
| DE2760007C2 (cs) * | 1977-06-07 | 1988-10-06 | Microbial Chem Res Found | |
| JPS6026099B2 (ja) * | 1977-09-21 | 1985-06-21 | 財団法人微生物化学研究会 | ペプチド、その酸附加塩およびその製造法 |
| CH653687A5 (de) * | 1978-11-25 | 1986-01-15 | Nippon Kayaku Kk | Threo-3-amino-2-hydroxy-butanoylaminoessigsaeure-derivate. |
| US4370318A (en) * | 1980-07-07 | 1983-01-25 | Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai | Bestatin-related compounds as immunopotentiator |
| JPS5767516A (en) * | 1980-09-24 | 1982-04-24 | Microbial Chem Res Found | Novel analgesic agent |
| JPH0810855Y2 (ja) * | 1989-07-20 | 1996-03-29 | タナシン電機株式会社 | オートリバース式テープレコーダ |
| JP3655629B2 (ja) * | 1993-06-29 | 2005-06-02 | 株式会社カネカ | 光学活性アミノアルコール誘導体及びその製法 |
| CN1073555C (zh) * | 1996-02-08 | 2001-10-24 | 日本化药株式会社 | 制备旋光性氰醇的方法 |
| SK16282000A3 (sk) * | 1998-05-01 | 2001-05-10 | Abbott Laboratories | Substituované beta-aminokyselinové inhibítory metionínaminopeptidázy-2 |
| US6242494B1 (en) | 1998-05-01 | 2001-06-05 | Abbott Laboratories | Substituted β-amino acid inhibitors of methionine aminopeptidase-2 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5439477B2 (cs) * | 1974-07-01 | 1979-11-28 |
-
1975
- 1975-07-22 GB GB30632/75A patent/GB1510477A/en not_active Expired
-
1976
- 1976-06-14 SE SE7606736A patent/SE431642B/xx not_active IP Right Cessation
- 1976-07-15 AU AU15912/76A patent/AU506003B2/en not_active Expired
- 1976-07-16 CS CS793519A patent/CS201034B2/cs unknown
- 1976-07-16 CS CS764736A patent/CS201033B2/cs unknown
- 1976-07-19 DE DE2632396A patent/DE2632396C2/de not_active Expired
- 1976-07-19 DE DE2660626A patent/DE2660626C2/de not_active Expired
- 1976-07-20 CA CA257,393A patent/CA1104156A/en not_active Expired
- 1976-07-21 JP JP8599276A patent/JPS52136118A/ja active Granted
- 1976-07-21 NL NL7608064A patent/NL7608064A/xx not_active Application Discontinuation
- 1976-07-21 FR FR7622279A patent/FR2318863A1/fr active Granted
- 1976-07-21 CH CH933676A patent/CH630892A5/de not_active IP Right Cessation
- 1976-07-22 HU HU76ZA395A patent/HU183048B/hu unknown
- 1976-07-22 DK DK331276A patent/DK149110C/da not_active IP Right Cessation
-
1980
- 1980-03-13 SE SE8001959A patent/SE452318B/sv unknown
-
1982
- 1982-04-22 JP JP57066233A patent/JPS6050780B2/ja not_active Expired
-
1983
- 1983-11-09 SE SE8306145A patent/SE8306145D0/xx not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| DK331276A (da) | 1977-01-23 |
| JPS5823654A (ja) | 1983-02-12 |
| NL7608064A (nl) | 1977-01-25 |
| SE8306145L (sv) | 1983-11-09 |
| SE8306145D0 (sv) | 1983-11-09 |
| DK149110C (da) | 1986-09-08 |
| AU506003B2 (en) | 1979-12-13 |
| SE7606736L (sv) | 1977-01-23 |
| JPS5758338B2 (cs) | 1982-12-09 |
| DE2632396C2 (de) | 1982-11-25 |
| HU183048B (en) | 1984-04-28 |
| AU1591276A (en) | 1978-01-19 |
| CA1104156A (en) | 1981-06-30 |
| SE452318B (sv) | 1987-11-23 |
| SE431642B (sv) | 1984-02-20 |
| FR2318863B1 (cs) | 1980-10-31 |
| CS201034B2 (en) | 1980-10-31 |
| SE8001959L (sv) | 1980-03-13 |
| FR2318863A1 (fr) | 1977-02-18 |
| GB1510477A (en) | 1978-05-10 |
| JPS52136118A (en) | 1977-11-14 |
| DK149110B (da) | 1986-01-27 |
| DE2660626C2 (de) | 1985-07-11 |
| JPS6050780B2 (ja) | 1985-11-11 |
| CS201033B2 (en) | 1980-10-31 |
| DE2632396A1 (de) | 1977-02-03 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased | ||
| PL | Patent ceased |