KR850004396A - 네오카르지노스타틴 유도체의 제조방법 - Google Patents
네오카르지노스타틴 유도체의 제조방법 Download PDFInfo
- Publication number
- KR850004396A KR850004396A KR1019840004738A KR840004738A KR850004396A KR 850004396 A KR850004396 A KR 850004396A KR 1019840004738 A KR1019840004738 A KR 1019840004738A KR 840004738 A KR840004738 A KR 840004738A KR 850004396 A KR850004396 A KR 850004396A
- Authority
- KR
- South Korea
- Prior art keywords
- esterified
- styrene
- neocardinostatin
- carbon atoms
- residue
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 6
- 229920000147 Styrene maleic anhydride Polymers 0.000 claims description 7
- PYSRRFNXTXNWCD-UHFFFAOYSA-N 3-(2-phenylethenyl)furan-2,5-dione Chemical compound O=C1OC(=O)C(C=CC=2C=CC=CC=2)=C1 PYSRRFNXTXNWCD-UHFFFAOYSA-N 0.000 claims description 4
- 238000002523 gelfiltration Methods 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims 7
- 229920001577 copolymer Polymers 0.000 claims 5
- 125000000217 alkyl group Chemical group 0.000 claims 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 4
- -1 ethylene glycol monoalkyl ether Chemical class 0.000 claims 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid group Chemical group C(\C=C/C(=O)O)(=O)O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims 2
- 125000003158 alcohol group Chemical group 0.000 claims 2
- 239000012736 aqueous medium Substances 0.000 claims 2
- 235000011187 glycerol Nutrition 0.000 claims 2
- QZGIWPZCWHMVQL-UIYAJPBUSA-N neocarzinostatin chromophore Chemical compound O1[C@H](C)[C@H](O)[C@H](O)[C@@H](NC)[C@H]1O[C@@H]1C/2=C/C#C[C@H]3O[C@@]3([C@@H]3OC(=O)OC3)C#CC\2=C[C@H]1OC(=O)C1=C(O)C=CC2=C(C)C=C(OC)C=C12 QZGIWPZCWHMVQL-UIYAJPBUSA-N 0.000 claims 2
- 239000011541 reaction mixture Substances 0.000 claims 2
- 125000003011 styrenyl group Chemical group [H]\C(*)=C(/[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 2
- 239000000758 substrate Substances 0.000 claims 2
- 229950009268 zinostatin Drugs 0.000 claims 2
- KPYCVQASEGGKEG-UHFFFAOYSA-N 3-hydroxyoxolane-2,5-dione Chemical group OC1CC(=O)OC1=O KPYCVQASEGGKEG-UHFFFAOYSA-N 0.000 claims 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 1
- 241000209140 Triticum Species 0.000 claims 1
- 235000021307 Triticum Nutrition 0.000 claims 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 238000000502 dialysis Methods 0.000 claims 1
- 238000001914 filtration Methods 0.000 claims 1
- 102000034238 globular proteins Human genes 0.000 claims 1
- 108091005896 globular proteins Proteins 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 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 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 235000012054 meals Nutrition 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 238000000108 ultra-filtration Methods 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S260/00—Chemistry of carbon compounds
- Y10S260/47—Poisons, foods, or pharmaceuticals
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
내용 없음
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 스티렌-말레산 무수물 공중합체의 NMR스펙트럼.
제2a 및 2b도는 겔투과 크로마토그래피.
제3도는 반응 생성물의 겔여과 프로필.
Claims (7)
- 수용성 매질에서 네오카르지노스타틴 과스 티린잔기반쪽이 에스테르화된 말레산 잔기(식중에서, R은 1∼4탄소원자를 갖는 알칸올로부터 수신기가 제거된 알코올, 알킬기가 1∼2탄소원자를 갖는 에틸렌글리콜 모노알킬에테르, 또는 알킬기가 1∼2탄소원자를 갖는 글리세린 디알킬 에테르이다);및 말라산 무수물 잔기로 구성되고, 하식(Ⅳ)와 (V)를 만족하는 부분적으로 반쪽이 에스테르화된스티렌-말레산 무수물 공중합체(식중에서는 상기 공중합체의 무게 평균 분자량이고은 상기 공중합체의 수평균 분자량이다)몰 과량과 반응시킴을 특징으로 하고, 반응혼합물을 게 여과하여 분리함을 특징으로 하는 하기 일반식 (A)의 네오카르지 노스타틴 유도체의 제조방법.(SMA)-(NCS)-(SMA) (A)식중에서, (NCS)는 네오카르지노스타틴의 N-터미날에서의 알라닌 잔기 및 네오카르지노스타틴의 N-터미날에서 20번째의 리신잔기중의 1차 아미노기 각각으로부터 수소원자 1개씩 제거된 2가의 네오카르노스타틴 잔기이고 (SMA)는 중량평균분자량이 800∼2,500이고, (a) 스티렌잔기(b) 반쪽이 에스테르화된 말레산 잔기(식중에서, R은 1∼4탄소원자를 갖는 알칸올로부터 수신기가 제거된 알코올, 알킬기가 1∼2탄소원자를 갖는 에틸렌글리콜 모노알킬 에테르, 또는 알킬기가 1∼2탄소원자를 갖는 글리세린 디알킬 에테르이다);(c) 말레산잔기; 및(d) 말레산 잔기중의 하나의 카르복실기의 수산기가 제거되어 네오카르지노스타틴 잔기에 결합된 하기 일반식을 갖는 잔기(식중에서, 카르보닐기 중의 탄소원자가 네오카르지노스타틴에 결합된다)로 구성되는 1가의 부분적으로 반쪽이 에스테르화된 스티렌-말레산 공중합잔기이다.
- 제1항에 있어서, 3∼15중량부의 부분적으로 반쪽이 에스테르화된 스티렌-말레산 무수물 공중합체와 네오카르지노스타틴 1중량부와 반응시킴을 특징으로 하는 방법.
- 제1항에 있어서, 반응계에 첨가된 네오카르지노스타틴과 부분적으로 반쪽이 에스테르화된 스티렌-말레산 무수물 공중합체의 전체농도가 10∼35중량%임을 특징으로 하는 방법.
- 제1항에 있어서, 수용성 매질의 pH가 7.5∼9.5임을 특징으로 하는 방법.
- 제1항에 있어서, 네오카르지노스타틴과 부분적으로 반쪽이 에스테르화된 말레산 무수물 공중합체와의 반응을 어두운 곳에서 15℃이하의 온도로 수행함을 특징으로 하는 방법.
- 제1항에 있어서, 네오카르지노스타틴과 부분적으로 반쪽이 에스테르화된 말레산 무수물 공중합체와의 반응이 완결된 후에 반응 혼합물을 밀 투석, 한외 여과 또는 겔여과로 정제한 후 겔여과하여 네오카르지노스타틴 유도체를 수득함을 특징으로 하는 방법.
- 제1항에 있어서, 겔여과를 분자량의 기준으로서 구상 단백질을 사용하여 제한 한계가 50,000∼150,000인 기질로부터 선택한 하나의 기질을 사용하여 수행함을 특징으로 하는 방법.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58-145418 | 1983-08-08 | ||
| JP58145418A JPS6075432A (ja) | 1983-08-08 | 1983-08-08 | ネオカルチノスタチン誘導体及びその製造方法 |
| JP145,418 | 1983-08-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR850004396A true KR850004396A (ko) | 1985-07-15 |
| KR860001965B1 KR860001965B1 (ko) | 1986-11-07 |
Family
ID=15384788
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019840004738A KR860001965B1 (ko) | 1983-08-08 | 1984-08-08 | 네오카르 지노스타틴 유도체의 제조 방법 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US4782113A (ko) |
| EP (1) | EP0136791B1 (ko) |
| JP (1) | JPS6075432A (ko) |
| KR (1) | KR860001965B1 (ko) |
| AT (1) | ATE41163T1 (ko) |
| CA (1) | CA1240315A (ko) |
| DE (1) | DE3477005D1 (ko) |
| ES (1) | ES8606410A1 (ko) |
| SU (1) | SU1428206A3 (ko) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2556865B2 (ja) * | 1986-09-19 | 1996-11-27 | 山之内製薬株式会社 | ネオカルチノスタチン誘導体の非注射投与用組成物 |
| US5389366A (en) * | 1986-09-19 | 1995-02-14 | Yamanouchi Pharmaceutical Co., Ltd. | Neocarzinostatin derivative composition for oral administration |
| JPH01156925A (ja) * | 1987-09-01 | 1989-06-20 | Yamanouchi Pharmaceut Co Ltd | ネオカルチノスタチン誘導体の凍結乾操製剤組成物 |
| CA1327161C (en) * | 1987-09-01 | 1994-02-22 | Mitsugu Kobayashi | Lyophilized pharmaceutical composition of neocarzinostatin derivative |
| AU2001252650A1 (en) * | 2000-04-28 | 2001-11-12 | Effector Cell Institute | Novel derivative of cell chemotactic factor |
| EP1386927B1 (en) | 2002-08-02 | 2005-03-30 | Institut Curie | Shiga toxin B-subunit as a vector for tumor diagnosis and drug delivery to GB3 expressing tumors |
| US9937152B2 (en) | 2013-11-19 | 2018-04-10 | Hiroshi Maeda | Derivative of styrene-maleic acid copolymer |
| WO2024170742A1 (en) * | 2023-02-17 | 2024-08-22 | Danmarks Tekniske Universitet | Copolymer-drug conjugate for treatment of tumours |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3085994A (en) * | 1959-10-30 | 1963-04-16 | Sinclair Research Inc | Chain terminated copolymer of styrene and maleic anhydride of low solution viscosity |
| US3121043A (en) * | 1960-05-11 | 1964-02-11 | Scient Associates Inc | Sustained release pharmaceutical preparation and methods for making same |
| US3245933A (en) * | 1960-05-19 | 1966-04-12 | Sinclair Research Inc | Styrene-maleic anhydride copolymers cross-linked with aliphatic polyhydroxy compounds |
| JPS6017206B2 (ja) * | 1977-03-24 | 1985-05-01 | 浩 前田 | ネオカルチノスタチン誘導体の製造法 |
| EP0087957B1 (en) * | 1982-02-27 | 1986-11-26 | Kuraray Co., Ltd. | Neocarzinostatin complexes, a method for producing the same, and an antitumor agent containing said complexes as an active component |
| JPS59139396A (ja) * | 1983-01-31 | 1984-08-10 | Kuraray Co Ltd | ネオカルチノスタチン複合体の製造方法 |
-
1983
- 1983-08-08 JP JP58145418A patent/JPS6075432A/ja active Granted
-
1984
- 1984-07-26 CA CA000459767A patent/CA1240315A/en not_active Expired
- 1984-08-07 SU SU843783009A patent/SU1428206A3/ru active
- 1984-08-07 ES ES534941A patent/ES8606410A1/es not_active Expired
- 1984-08-08 DE DE8484305413T patent/DE3477005D1/de not_active Expired
- 1984-08-08 KR KR1019840004738A patent/KR860001965B1/ko not_active IP Right Cessation
- 1984-08-08 EP EP84305413A patent/EP0136791B1/en not_active Expired
- 1984-08-08 AT AT84305413T patent/ATE41163T1/de not_active IP Right Cessation
-
1986
- 1986-09-25 US US06/911,454 patent/US4782113A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| US4782113A (en) | 1988-11-01 |
| JPH0133119B2 (ko) | 1989-07-11 |
| KR860001965B1 (ko) | 1986-11-07 |
| EP0136791A3 (en) | 1985-12-18 |
| SU1428206A3 (ru) | 1988-09-30 |
| EP0136791B1 (en) | 1989-03-08 |
| JPS6075432A (ja) | 1985-04-27 |
| ES534941A0 (es) | 1986-04-01 |
| ES8606410A1 (es) | 1986-04-01 |
| EP0136791A2 (en) | 1985-04-10 |
| CA1240315A (en) | 1988-08-09 |
| DE3477005D1 (en) | 1989-04-13 |
| ATE41163T1 (de) | 1989-03-15 |
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