KR100653153B1 - 수용성 중합체의 입체장애 유도체 - Google Patents
수용성 중합체의 입체장애 유도체 Download PDFInfo
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- KR100653153B1 KR100653153B1 KR1020027008015A KR20027008015A KR100653153B1 KR 100653153 B1 KR100653153 B1 KR 100653153B1 KR 1020027008015 A KR1020027008015 A KR 1020027008015A KR 20027008015 A KR20027008015 A KR 20027008015A KR 100653153 B1 KR100653153 B1 KR 100653153B1
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- C08G65/32—Polymers modified by chemical after-treatment
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- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/331—Polymers modified by chemical after-treatment with organic compounds containing oxygen
- C08G65/332—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof
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- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/331—Polymers modified by chemical after-treatment with organic compounds containing oxygen
- C08G65/332—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof
- C08G65/3322—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof acyclic
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- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/333—Polymers modified by chemical after-treatment with organic compounds containing nitrogen
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Abstract
Description
Claims (38)
- 제 1 항에 있어서, 상기 수용성 비펩티드계 중합체 골격이 폴리(알킬렌 글리콜), 폴리(옥시에틸화 폴리올), 폴리(올레핀계 알콜), 폴리(비닐피롤리돈), 폴리(히드록시프로필메타크릴아미드), 폴리(α-히드록시산), 폴리(비닐 알콜), 폴리포스파젠, 폴리옥사졸린, 폴리(N-아크릴로일모르폴린), 및 이들의 공중합체, 삼원중합체 및 혼합물로 구성된 군으로부터 선택되는 중합체.
- 제 1 항에 있어서, 수용성 비펩티드계 중합체가 폴리(에틸렌 글리콜) 인 중합체.
- 제 3 항에 있어서, 폴리(에틸렌 글리콜) 이 약 200 Da 내지 약 100,000 Da 의 평균 분자량을 갖는 중합체.
- 제 1 항에 있어서, 수용성 비펩티드계 중합체가 약 2 내지 약 300 개의 말단을 갖는 중합체.
- 제 1 항에 있어서, Z 가 C1 - C8 알킬 또는 치환 알킬인 중합체.
- 제 1 항에 있어서, Z 가 메틸, 에틸, n-프로필, 이소프로필, n-부틸, 이소부틸, sec-부틸, t-부틸 및 벤질로 구성된 군으로부터 선택되는 중합체.
- 제 1 항에 있어서, m 이 1 내지 약 10 인 중합체.
- 제 1 항에 있어서, X 가 염소, 브롬, N-숙신이미딜옥시, 술포-N-숙신이미딜옥시, 1-벤조트리아졸릴옥시, 히드록실, 1-이미다졸릴 및 p-니트로페닐옥시로 구성된 군으로부터 선택되는 중합체.
- 제 10 항에 있어서, R' 이 메톡시인 중합체.
- 제 10 항에 있어서, R' 이 히드록실, 보호 히드록실, 활성 에스테르, 활성 카르보네이트, 아세탈, 알데히드, 알데히드 히드레이트, 알케닐, 아크릴레이트, 메타크릴레이트, 아크릴아미드, 활성 술폰, 아민, 보호 아민, 히드라지드, 보호 히드라지드, 티올, 보호 티올, 카르복실산, 보호 카르복실산, 이소시아네이트, 이소티오시아네이트, 말레이미드, 비닐술폰, 디티오피리딘, 비닐피리딘, 요오도아세트아미드, 에폭시드, 글리옥살, 디온, 메실레이트, 토실레이트 및 트레실레이트로 구성된 군으로부터 선택되는 관능기인 중합체.
- 제 10 항에 있어서, R' 이 -W-D (식 중, W 는 링커이고, D 는 생물학 활성제이다) 인 중합체.
- 제 10 항에 있어서, R' 이 -Q(CH2)mCHZC(O)X (식 중, Q, m, Z 및 X 는 상기에 정의된 바와 같다) 인 중합체.
- 제 10 항에 있어서, POLY 가 폴리(에틸렌 글리콜) 인 중합체.
- 제 15 항에 있어서, 폴리(에틸렌 글리콜) 이 약 200 Da 내지 약 100,000 Da 의 평균 분자량을 갖는 중합체.
- 제 10 항에 있어서, Z 가 C1 - C8 알킬 또는 치환 알킬인 중합체.
- 제 10 항에 있어서, Z 가 메틸, 에틸, n-프로필, 이소프로필, n-부틸, 이소부틸, sec-부틸, t-부틸 및 벤질로 구성된 군으로부터 선택되는 중합체.
- 제 10 항에 있어서, m 이 1 내지 약 10 인 중합체.
- 제 10 항에 있어서, X 가 히드록실인 중합체.
- 제 21 항에 있어서, POLY 가 폴리(에틸렌 글리콜) 인 중합체.
- 제 22 항에 있어서, POLY 가 약 200 Da 내지 약 100,000 Da 의 평균 분자량을 갖는 중합체.
- 제 24 항에 있어서, X 가 히드록실인 중합체.
- 제 1 항의 중합체를 생물학 활성제에 공유 부착시켜 수득되는 생물학 활성 중합체 콘쥬게이트.
- 제 27 항에 있어서, W 가 O, S 및 NH 로 구성된 군으로부터 선택되는 생물학 활성 중합체 콘쥬게이트.
- 제 27 항에 있어서, D 가 펩티드, 단백질, 효소, 소분자 약물, 염료, 지질,뉴클레오시드, 올리고뉴클레오티드, 세포, 바이러스, 리포좀, 미립 및 마이셀 (micelle) 로 구성된 군으로부터 선택되는 생물학 활성 중합체 콘쥬게이트.
- 제 27 항에 있어서, 상기 수용성 비펩티드계 중합체 골격이 폴리(알킬렌 글리콜), 폴리(옥시에틸화 폴리올), 폴리(올레핀계 알콜), 폴리(비닐피롤리돈), 폴리(히드록시프로필메타크릴아미드), 폴리(α-히드록시산), 폴리(비닐 알콜), 폴리포스파젠, 폴리옥사졸린, 폴리(N-아크릴로일모르폴린), 및 이들의 공중합체, 삼원중합체 및 혼합물로 구성된 군으로부터 선택되는 생물학 활성 중합체 콘쥬게이트.
- 제 27 항에 있어서, 상기 수용성 비펩티드계 중합체가 폴리(에틸렌 글리콜)인 생물학 활성 중합체 콘쥬게이트.
- 제 27 항에 있어서, Z 가 C1-C8 알킬 또는 치환 알킬인 생물학 활성 중합체 콘쥬게이트.
- 제 27 항에 있어서, Z 가 메틸, 에틸, n-프로필, 이소프로필, n-부틸, 이소부틸, sec-부틸, t-부틸 및 벤질로 구성된 군으로부터 선택되는 생물학 활성 중합체 콘쥬게이트.
- 제 27 항에 있어서, m 이 1 내지 약 10 인 생물학 활성 중합체 콘쥬게이트.
- 제 27 항에 있어서, W 가 중합체 골격에 활성 제제를 부착하기 위해 이용되는 활성제의 관능기의 잔기인 생물학 활성 중합체 콘쥬게이트.
- 하기를 포함하는, 생물학 활성 중합체 콘쥬게이트의 제조 방법:하기 구조에 공유 결합되는 하나 이상의 말단을 갖는 중합체 골격을 포함하는, 수용성 비펩티드계 중합체를 제공:[화학식 I](식 중:L 은 중합체 골격 말단으로의 결합점이며;Q 는 O 또는 S 이고;m 은 1 내지 약 20 이고;Z 는 알킬, 치환 알킬, 아릴 및 치환 아릴로 구성된 군으로부터 선택되고;X 는 이탈기이다),중합체와 생물학 활성제를 반응시켜 하기 구조에 공유 결합되는 하나 이상의 말단을 갖는 생물학 활성 중합체 콘쥬게이트를 형성:(식 중:L 은 중합체 골격 말단으로의 결합점이며;Q 는 O 또는 S 이고;m 은 1 내지 약 20 이고;Z 는 알킬, 치환 알킬, 아릴 및 치환 아릴로 구성된 군으로부터 선택되고;W 는 링커이고;D 는 생물학 활성제이다).
- 제 36 항에 있어서, W 가 O, S 및 NH 로 구성된 군으로부터 선택되는 방법.
- 제 36 항에 있어서, D 가 펩티드, 단백질, 효소, 소분자 약물, 염료, 지질, 뉴클레오시드, 올리고뉴클레오티드, 세포, 바이러스, 리포좀, 미립 및 마이셀로 구성된 군으로부터 선택되는 방법.
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US17178499P | 1999-12-22 | 1999-12-22 | |
US60/171,784 | 1999-12-22 |
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KR20020074459A KR20020074459A (ko) | 2002-09-30 |
KR100653153B1 true KR100653153B1 (ko) | 2006-12-01 |
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US (8) | US6495659B2 (ko) |
EP (1) | EP1259562B1 (ko) |
JP (1) | JP4861586B2 (ko) |
KR (1) | KR100653153B1 (ko) |
AT (1) | ATE317868T1 (ko) |
AU (1) | AU781839B2 (ko) |
CA (1) | CA2394980C (ko) |
CY (1) | CY1107463T1 (ko) |
DE (1) | DE60026073T2 (ko) |
DK (1) | DK1259562T3 (ko) |
ES (1) | ES2256082T3 (ko) |
MX (1) | MXPA02006216A (ko) |
WO (1) | WO2001046291A1 (ko) |
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PT1121156E (pt) | 1998-10-16 | 2006-05-31 | Biogen Idec Inc | Conjugados de polimeros de interferao-beta-1a e as suas utilizacoes |
DE69931507T2 (de) | 1998-10-16 | 2007-01-11 | Biogen Idec Ma Inc., Cambridge | Interferon-beta fusionsproteine und deren verwendungen |
EP1259562B1 (en) * | 1999-12-22 | 2006-02-15 | Nektar Therapeutics Al, Corporation | Sterically hindered derivatives of water soluble polymers |
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US7053150B2 (en) | 2000-12-18 | 2006-05-30 | Nektar Therapeutics Al, Corporation | Segmented polymers and their conjugates |
SI1436012T1 (en) * | 2001-10-18 | 2018-03-30 | Nektar Therapeutics | Polymer conjugates of opioid antagonists |
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KR100967334B1 (ko) * | 2002-09-09 | 2010-07-05 | 넥타르 테라퓨틱스 | 말단 카르복실산을 가진 수용성 중합체 유도체의 제조 방법 |
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EP1259562B1 (en) | 1999-12-22 | 2006-02-15 | Nektar Therapeutics Al, Corporation | Sterically hindered derivatives of water soluble polymers |
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2000
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