KR950701331A - 신규한 시크릭 아기노산 및 그의 유도체(Novel Cyclic Acids Amino and Derivatives Thereof) - Google Patents

신규한 시크릭 아기노산 및 그의 유도체(Novel Cyclic Acids Amino and Derivatives Thereof)

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KR950701331A
KR950701331A KR1019940703746A KR19940703746A KR950701331A KR 950701331 A KR950701331 A KR 950701331A KR 1019940703746 A KR1019940703746 A KR 1019940703746A KR 19940703746 A KR19940703746 A KR 19940703746A KR 950701331 A KR950701331 A KR 950701331A
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amino
acetic acid
hydrogen
compound
aryl
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블라디미르 베일린
휴아이 구 첸
옴 프라카쉬 고엘
마크 유진 마르래트
존 고돈 톱리스
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프란시스 제이. 티니
워너-램버트 캄파니
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/78—Ring systems having three or more relevant rings
    • C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
    • C07D311/82—Xanthenes
    • C07D311/90—Xanthenes with hydrocarbon radicals, substituted by amino radicals, directly attached in position 9
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    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/51—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
    • C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D335/10—Dibenzothiopyrans; Hydrogenated dibenzothiopyrans
    • C07D335/12—Thioxanthenes
    • C07D335/20—Thioxanthenes with hydrocarbon radicals, substituted by amino radicals, directly attached in position 9
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/30—Ortho- or ortho- and peri-condensed systems containing three rings containing seven-membered rings
    • C07C2603/32—Dibenzocycloheptenes; Hydrogenated dibenzocycloheptenes

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

본 발명에 따라서 생물학적 활성 펩티드를 제조하는데 유용한 신규한 시클릭 아미노산 및 시클릭 아미노산의 D 및 L 에난티오머의 제조 방법이 제공된다. 라세미 시클릭 아미노산의 N-보호된 유도체는 (-)신코니딘으로 처리되며 생성된 염은 목적하는 에난티오머 및 그의 유도체 및 방법에 사용되는 유용한 중간체로 분해된다.

Description

신규한 시크릭 아기노산 및 그의 유도체(Novel Cyclic Amino Acids and Derivatives Thereof)
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (12)

  1. 하기 일반식(Ⅰ)의 화합물 또는 그의 제약학상 허용되는 염.
    상기 식 중, Z는 -O, -S(O)n-(여기서, n은 0내지 2의 정수임),(여기서, R3은 수소, 알킬, 알케닐, 알키닐, 시클로알킬, 시클로알킬알킬, 아릴, 헤테로아릴, 플루오레닐메틸, CX3(여기서, X는 할로겐 또는 아릴임), -(CH2)m-(여기서, m은 1내지 4의 정수임).
    R은 수소, 메틸, 트리플루오로메틸, 메톡시, 히드록시, 클로로, 브로모, 플루오로, 요오도, 2, 4-디브로모, 2,4-디클로로 및 2,4-디플루오로이고; R1은 수소, 알킬, 알케닐, 알키닐, 시크로알킬, 시클로알킬알킬, 아릴, 아릴알킬, 헤테로아릴 및 플루오레닐메틸이고; R2은 수소, 벤질옥시카르보닐, tert-부틸옥시카르보닐, 플루오레닐옥시카르보닐, 1-아다만틸옥시카르보닐, 2-아다만틸옥시카르보닐, 및(여기서, R3은 상기 정의한 바와 같음)이고; C*에서의 입체화학은 D, L 또는 D이다. 단, 여기서 Z가 -O-이고, R, R1및 R2가 수소이고, C*에서의 입체화학이 DL인 일반식(Ⅰ)의 화합물은 제외한다.
  2. 제1항에 있어서, Z가 -O-, -S-,(여기서, R3은 수소 또는 알킬임),
    -(CH2)m-(여기서, m은 1내지 4의 정수임) 및 -(CHH)n-CH=CH-(CH2)n- (여기서, n은 0 또는 1의 정수임)이고; R이 수소이고; R1가 수소, 벤질옥시 카르보닐, tert-부틸옥시카르보닐, 플루오레닐옥시카르보닐, 1-아다만틸옥시카르보닐 및 2-아다만틸록시카르보닐인 화합물.
  3. 제2항에 있어서, Z가 -O-, -S-,(여기서, R3은 수소 또는 알킬임),
    -CH2CH2- 및 -CH=CH-인 화합물.
  4. 제3항에 있어서, D-α-아미노산-9H-크산텐-9-아세트산; L-α-아미노-9H-크산텐-9-아세트산; L-α-아미노-9H-티오크산텐-9-아세트산; L-α-아미노-9H-티오크산텐-9-아세트산; DL-α-아미노-9H-티오크산텐-9-아세트산; D-α-아미노-10,11-디히드로-5H-디벤조[a,b]시클로헵탄-5-아세트산; L-α-아미노-10,11-디히드로-5H-디벤조[a,b]시클로헵탄-5-아세트산; DL-α-아미노-10,11-디히드로-5H-디벤조[a,b]시클로헵탄-5-아세트산; D-α-아미노-5H-디벤조[a,b]시클로헵탄-5-아세트산; L-α-아미노-5H-디벤조[a,b]시클로헵탄-5-아세트산; 및 DL-α-아미노-5H-디벤조[a,b]시클로헵탄-5-아세트산으로 이루어진 군에서 선택된 화합물.
  5. (a)하기 일반식(Ⅱ)의 라세미 화합물을 용매 중에서 (-)신코니딘으로 처리하여 하기 일반식(Ⅲ)의 라세미 화합물을 얻는 단계; (b)하기 일반식(Ⅲ)의 화합물을 분별 결정화에 의해 D 및 L 에난티오머로 분리하는 단계; (c)하기 일반식(D-Ⅲa) 또는 (L-Ⅲb)의 화합물을 용매 중에서 산으로 처리하여 하기 일반식(D-Ⅱa) 또는 (L-Ⅱb)의 화합물을 얻는 단계; (d)일반식 (D-Ⅱa) 또는 (L-Ⅱb)의 화합물을 산과 함께 가열하여 일반식( )의 (D-Ⅰa) 또는 (L-Ⅰb) 에난티오머를 얻는 단계; 및 (e)필요시에, 일반식((D-Ⅰa) 또는 (L-Ⅰb)의 화합물을 통상의 방법으로 대응하는 제약학상 허용되는 염으로 전환시키고, 또한 필요시에 대응하는 제약학상 허용되는 염을 통상의 방법으로 일반식 (D-Ⅰa) 또는 (L-Ⅰb)의 화합물로 전환시키는 단계로 이루어지는 하기 일반식(Ⅰ)의 화합물 또는 그의 제약학상 허용되는 염의 D 및 L 에난티오머의 제조방법.
    상기 식 중, Z는 -O, -S(O)n-(여기서, n은 0내지 2의 정수임),(여기서, R3은 수소, 알킬, 알케닐, 알키닐, 시클로알킬, 시클로알킬알킬, 아릴, 헤테로아릴, 플루오레닐메틸, CX3(여기서, X는 할로겐 또는 아릴임), -(CH2)m-(여기서, m은 1내지 4의 정수임).
    R은 수소, 메틸, 트리플루오로메틸, 메톡시, 히드록시, 클로로, 브로모, 플루오로, 요오도, 2, 4-디브로모, 2,4-디클로로 및 2,4-디플루오로이고; R1은 수소, 알킬, 알케닐, 알키닐, 시크로알킬, 시클로알킬알킬, 아릴, 아릴알킬, 헤테로아릴 및 플루오레닐메틸이고; R4은 저급 알킬 및 CX3(여기서, X는 수소, 할로겐 또는 아릴임)이다.
  6. 제5항에 있어서, 단계 (a)에 사용된 용매가 메탄올인 방법.
  7. 제5항에 있어서, 단계 (b)에 사용된 용매가 에틸 아세테이트인 방법.
  8. 제5항에 있어서, 단계 (c)에 사용된 산이 염산인 방법.
  9. 제5항에 있어서, 단계 (d)에 사용된 산이 염산인 방법.
  10. 제5항에 있어서, 일반식(D-Ⅱa) 또는 (L-Ⅱb)의 화합물을 6N 염산 용액에서 환류시키는 방법.
  11. D-α-아미노산-9H-크산텐-9-아세트산; L-α-아미노-9H-크산텐-9-아세트산; L-α-아미노-9H-티오크산텐-9-아세트산; L-α-아미노-9H-티오크산텐-9-아세트산; D-α-아미노-10,11-디히드로-5H-디벤조[a,b]시클로헵탄-5-아세트산; L-α-아미노-10,11-디히드로-5H-디벤조[a,b]시클로헵탄-5-아세트산; D-α-아미노-5H-디벤조[a,b]시클로헵탄-5-아세트산; 및 L-α-아미노-5H-디벤조[a,b]시클로헵탄-5-아세트산으로 이루어진 군에서 선택된 화합물의 제조를 위한 방법.
  12. 하기 일반식(D-Ⅲa) 및 (L-Ⅲb)로 이루어진 군에서 선택된 화합물.
    상기 식 중, Z는 -O, -S(O)n-(여기서, n은 0내지 2의 정수임),(여기서, R3은 수소, 알킬, 알케닐, 알키닐, 시클로알킬, 시클로알킬알킬, 아릴, 헤테로아릴, 플루오레닐메틸, CX3(여기서, X는 할로겐 또는 아릴임), -(CH2)m-(여기서, m은 1내지 4의 정수임).
    R은 수소, 메틸, 트리플루오로메틸, 메톡시, 히드록시, 클로로, 브로모, 플루오로, 요오도, 2, 4-디브로모, 2,4-디클로로 및 2,4-디플루오로이고; R1은 수소, 알킬, 알케닐, 알키닐, 시크로알킬, 시클로알킬알킬, 아릴, 아릴알킬, 헤테로아릴 및 플루오레닐메틸이고; R4은 저급 알킬 및 CX3(여기서, X는 수소, 할로겐 또는 아릴임)이다.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019940703746A 1992-04-22 1993-04-16 신규한 시클릭 아미노산 및 그의 유도체 KR100269758B1 (ko)

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KR1020007001540A KR100270305B1 (ko) 1992-04-22 1993-04-16 신규한 시클릭 아미노산 및 그의 유도체

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US872742 1992-04-22
US07/872,742 US5264577A (en) 1992-04-22 1992-04-22 Cyclic amino acids and derivatives thereof
US872,742 1992-04-22
PCT/US1993/003657 WO1993021176A1 (en) 1992-04-22 1993-04-16 Novel cyclic amino acids and derivatives thereof

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KR1020007001541A Division KR100270306B1 (ko) 1992-04-22 1993-04-16 신규한 시클릭 아미노산 및 그의 유도체

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KR100269758B1 KR100269758B1 (ko) 2000-11-01

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KR1020007001541A KR100270306B1 (ko) 1992-04-22 1993-04-16 신규한 시클릭 아미노산 및 그의 유도체
KR1020007001540A KR100270305B1 (ko) 1992-04-22 1993-04-16 신규한 시클릭 아미노산 및 그의 유도체

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KR1020007001540A KR100270305B1 (ko) 1992-04-22 1993-04-16 신규한 시클릭 아미노산 및 그의 유도체

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Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5550110A (en) * 1992-04-22 1996-08-27 Warner-Lambert Company Endothelin Antagonists II
US5264577A (en) * 1992-04-22 1993-11-23 Warner-Lambert Company Cyclic amino acids and derivatives thereof
US5663368A (en) * 1993-07-14 1997-09-02 Smithkline Beecham Corporation Synthesis of acid addition salts of hydroxylamines
US5498719A (en) * 1994-01-31 1996-03-12 The United States Of America As Represented By The Secretary Of The Department Of Health & Human Services Diastereoselective process leading to a key intermediate for the preparation of fluorinated reverse transcriptase inhibitors
US5623087A (en) * 1995-03-10 1997-04-22 Ndsu-Research Foundation Method for preparation of optically active diarylalanines
GB9621789D0 (en) * 1996-10-18 1996-12-11 Lilly Industries Ltd Pharmaceutical compounds
GB9626151D0 (en) * 1996-12-17 1997-02-05 Lilly Industries Ltd Pharmaceutical compounds
ES2189523T3 (es) * 1998-11-20 2003-07-01 Schering Corp Alquilacion enantioselectiva de compuestos triciclicos.
US6307048B1 (en) 1998-11-20 2001-10-23 Schering Corporation Enantioselective alkylation of tricyclic compounds
MXPA04005570A (es) * 2001-12-11 2004-12-06 Wyeth Corp Proceso para sintesis de beta-amino-alcoholes quiralmente puros.
AU2002351170B8 (en) * 2001-12-11 2009-10-08 Wyeth Production of chirally pure alpha-amino acids and N-sulfonyl alpha-amino acids
CN101633625B (zh) * 2008-07-23 2013-02-13 江苏恒瑞医药股份有限公司 R-β-氨基苯丁酸衍生物的制备方法
CN115073314A (zh) * 2022-07-11 2022-09-20 吉尔多肽生物制药(大连市)有限公司 一种仲碳类甘氨酸的合成方法

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3888900A (en) * 1971-08-17 1975-06-10 Sandoz Ag 7-cyano-hexahydro pleiadenes
NL7306069A (ko) * 1973-05-02 1974-11-05
FI57743C (fi) * 1979-03-29 1980-10-10 Orion Yhtymae Oy Foerfarande foer framstaellning av nya 1,8-dihydroxi-10-acyl-9-antroner mot psoriasis
JPS5810525A (ja) * 1981-06-15 1983-01-21 Sagami Chem Res Center 光学活性な１−芳香族基置換−１−アルカノン類の製造方法
EP0077754B1 (en) * 1981-10-16 1990-09-26 Sandoz Ag Novel pharmaceutically active 1,2,3,4,4a,5,10,10a-octahydrobenzo(g)quinoline derivatives
FR2580631B1 (fr) * 1985-04-17 1987-05-29 Cird Hydroxy-1 acyloxy-8 acyl-10 anthrones, leur procede de preparation et leur utilisation en medecine humaine ou veterinaire et en cosmetique
US4766109A (en) * 1986-10-17 1988-08-23 Schering Corporation Hydrophobic peptides
US4810636A (en) * 1986-12-09 1989-03-07 Miles Inc. Chromogenic acridinone enzyme substrates
US4851536A (en) * 1987-05-07 1989-07-25 American Home Products Corporation Cyclohexylquinolines as inhibitors of interleukin 1
US5101059A (en) * 1989-12-05 1992-03-31 Research Corporation Technologies, Inc. Amino acid protecting groups
US5198548A (en) * 1992-01-30 1993-03-30 Warner-Lambert Company Process for the preparation of D(-) and L(+)-3,3-diphenylalanine and D(-) and L(+)-substituted 3,3-diphenylalanines and derivatives thereof
US5264577A (en) * 1992-04-22 1993-11-23 Warner-Lambert Company Cyclic amino acids and derivatives thereof
DE4231636A1 (de) * 1992-09-22 1994-03-24 Beiersdorf Ag Neue in 10-Stellung substituierte Anthron- und Anthracen-Derivate, Verfahren zu deren Herstellung, diese Verbindungen enthaltende pharmazeutische oder kosmetische Mittel und deren Verwendung

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US5264577A (en) 1993-11-23
MX9302327A (es) 1993-10-01
SK282479B6 (sk) 2002-02-05
NZ252854A (en) 1995-11-27
JPH07506100A (ja) 1995-07-06
JP3276960B2 (ja) 2002-04-22
CA2133089C (en) 2004-06-29
AU4290393A (en) 1993-11-18
FI944906A (fi) 1994-10-19
NO304828B1 (no) 1999-02-22
CZ288529B6 (cs) 2001-07-11
KR100269758B1 (ko) 2000-11-01
EP0637305A1 (en) 1995-02-08
NO944014D0 (no) 1994-10-21
SK128694A3 (en) 1995-05-10
RU2111206C1 (ru) 1998-05-20
AU672209B2 (en) 1996-09-26
NO944014L (no) 1994-12-21
KR100270306B1 (ko) 2000-10-16
US5449778A (en) 1995-09-12
WO1993021176A1 (en) 1993-10-28
FI944906A0 (fi) 1994-10-19
CA2133089A1 (en) 1993-10-28
CZ256894A3 (en) 1995-04-12
KR100270305B1 (ko) 2000-10-16
RU94046047A (ru) 1996-09-27
US5380925A (en) 1995-01-10

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