KR20000049048A - 인터루킨-1β 전환 효소의 아스파르테이트 에스테르 억제제 - Google Patents

인터루킨-1β 전환 효소의 아스파르테이트 에스테르 억제제 Download PDF

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KR20000049048A
KR20000049048A KR1019990703117A KR19997003117A KR20000049048A KR 20000049048 A KR20000049048 A KR 20000049048A KR 1019990703117 A KR1019990703117 A KR 1019990703117A KR 19997003117 A KR19997003117 A KR 19997003117A KR 20000049048 A KR20000049048 A KR 20000049048A
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South Korea
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oxo
pentanoic acid
acetoxy
naphthalen
phenyl
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KR1019990703117A
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English (en)
Korean (ko)
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한스 페. 알브레히트
해미쉬 존 알렌
케니쓰 데일 브래디
브래들리 윌리암 캐프레이드
존 로쥐 길모어
윌리암 글렌 하터
쉐릴 진 헤이스
캐서린 로즈 코스틀란
엘리자베쓰 앤 루니
킴벌리 수잔 파라
앤쏘니 제롬 토마스
니겔 워커
Original Assignee
로즈 암스트롱, 크리스틴 에이. 트러트웨인
워너-램버트 캄파니
스타르크, 카르크
바스프 악티엔게젤샤프트
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Publication of KR20000049048A publication Critical patent/KR20000049048A/ko

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    • C07D239/08—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms directly attached in position 2
    • C07D239/10—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • 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
    • C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
    • 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
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
    • C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms

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KR1019990703117A 1996-10-11 1997-10-09 인터루킨-1β 전환 효소의 아스파르테이트 에스테르 억제제 KR20000049048A (ko)

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Families Citing this family (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000002858A1 (en) * 1998-07-08 2000-01-20 Harbor Branch Oceanographic Institution, Inc. Aminoiminoquinone and aminoquinine alkaloid compounds as capase inhibitors
US6339101B1 (en) * 1998-08-14 2002-01-15 Gpi Nil Holdings, Inc. N-linked sulfonamides of N-heterocyclic carboxylic acids or isosteres for vision and memory disorders
ATE363465T1 (de) * 1999-04-09 2007-06-15 Cytovia Inc Caspase inhibitoren und ihre verwendung
SI20876B (sl) * 1999-05-07 2009-08-31 Texas Biotechnology Corp Derivati propanojske kisline, ki inhibirajo vezavo integrinov na njihove receptorje
US6723711B2 (en) 1999-05-07 2004-04-20 Texas Biotechnology Corporation Propanoic acid derivatives that inhibit the binding of integrins to their receptors
AR026748A1 (es) * 1999-12-08 2003-02-26 Vertex Pharma Un compuesto inhibidor de caspasas, una composicion farmaceutica que lo comprende, un metodo para la sintesis del mismo y un compuesto intermediario paradicha sintesis
PT1268425E (pt) 2000-03-29 2008-04-01 Vertex Pharma Inibidores de caspase do grupo do carbamato e as suas utilizações
SI1268425T1 (sl) 2000-03-29 2008-04-30 Vertex Pharma Zaviralci karbamat kaspaze in uporaba le-teh
PE20011350A1 (es) 2000-05-19 2002-01-15 Vertex Pharma PROFARMACO DE UN INHIBIDOR DE ENZIMA CONVERTIDORA DE INTERLEUCINA-1ß (ICE)
WO2001094351A1 (en) * 2000-06-07 2001-12-13 Vertex Pharmaceuticals Incorporated Caspase inhibitors and uses thereof
US6355666B1 (en) 2000-06-23 2002-03-12 Medinox, Inc. Protected forms of pharmacologically active agents and uses therefor
EP1317414A2 (en) * 2000-09-08 2003-06-11 Merck Frosst Canada & Co. Gamma-ketoacid dipeptides as inhibitors of caspase-3
JP2004509120A (ja) * 2000-09-13 2004-03-25 バーテックス　ファーマシューティカルズ　インコーポレイテッド カスパーゼ阻害剤およびそれらの用途
AU2007201841B2 (en) * 2000-09-13 2008-09-04 Vertex Pharmaceuticals Incorporated Caspase Inhibitors and Uses Thereof
EP1318997B1 (en) 2000-09-15 2006-05-31 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
US6660731B2 (en) 2000-09-15 2003-12-09 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
IL156368A0 (en) 2000-12-21 2004-01-04 Vertex Pharma Pyrazole derivatives and pharmaceutical compositions containing the same
EP1381602A1 (en) * 2001-04-19 2004-01-21 Vertex Pharmaceuticals Incorporated Heterocyclyldicarbamides as caspase inhibitors
JP4428926B2 (ja) * 2001-05-23 2010-03-10 バーテックス ファーマシューティカルズ インコーポレイテッド カスパーゼインヒビターおよびそれらの使用
US6878743B2 (en) 2001-09-18 2005-04-12 Sunesis Pharmaceuticals, Inc. Small molecule inhibitors of caspases
MY141867A (en) 2002-06-20 2010-07-16 Vertex Pharma Substituted pyrimidines useful as protein kinase inhibitors
CN100503572C (zh) 2002-06-28 2009-06-24 沃泰克斯药物股份有限公司 天冬氨酸特异性半胱氨酸蛋白酶抑制剂及其用途
WO2004013140A1 (en) 2002-08-02 2004-02-12 Vertex Pharmaceuticals Incorporated Pyrazole compositions useful as inhibitors of gsk-3
TW200500343A (en) 2002-12-20 2005-01-01 Vertex Pharma Caspase inhibitors and uses thereof
PE20050159A1 (es) * 2003-05-27 2005-04-19 Vertex Pharma Derivados de acido 3-[2-(3-amino-2-oxo-2h-piridin-1-il)-acetilamino]-4-oxo-pentanoico como inhibidores de caspasa
PT2399915E (pt) 2004-03-12 2015-03-30 Vertex Pharma Processo e intermediários para a preparação de inibidores de caspase de acetal de ácido aspártico
WO2005115362A1 (en) 2004-05-15 2005-12-08 Vertex Pharmaceuticals Incorporated Treating seizures using ice inhibitors
CA2567080A1 (en) 2004-05-27 2005-12-15 Vertex Pharmaceuticals Incorporated Ice inhibitors for the treatment of autoinflammatory diseases
AU2005309776B2 (en) 2004-11-24 2011-12-22 Vertex Pharmaceuticals Incorporated 3-[2-(3-acylamino-2-oxo-2h-pyridin-1-yl)-acetylamino]-4-oxo-pentanoic acid derivatives and their use as caspase inhibitors
ATE529430T1 (de) 2005-07-28 2011-11-15 Vertex Pharma Caspase-hemmer-propharmaka
US7507842B2 (en) 2005-08-12 2009-03-24 Radiorx, Inc. Cyclic nitro compounds, pharmaceutical compositions thereof and uses thereof
SG166828A1 (en) 2005-11-03 2010-12-29 Vertex Pharma Aminopyrimidines useful as kinase inhibitors
CN101209976B (zh) * 2006-12-29 2012-01-11 中国人民解放军军事医学科学院毒物药物研究所 取代的酒石酸衍生物及其用于制备β-分泌酶抑制剂的用途
EP2152694A2 (en) 2007-05-02 2010-02-17 Vertex Pharmaceuticals Incorporated Thiazoles and pyrazoles useful as kinase inhibitors
EP2176261B1 (en) 2007-07-31 2012-12-19 Vertex Pharmaceuticals Incorporated Process for preparing 5-fluoro-1h-pyrazolo [3, 4-b] pyridin-3-amine and derivatives thereof
WO2010027921A1 (en) 2008-09-03 2010-03-11 Vertex Pharmaceuticals Incorporated Co-crystals and pharmaceutical formulations comprising the same
JP5980790B2 (ja) 2010-11-05 2016-08-31 ブランダイス ユニバーシティＢｒａｎｄｅｉｓ Ｕｎｉｖｅｒｓｉｔｙ バイオマーカーとしての、ｉｃｅ切断されたアルファ−シヌクレイン
US9956260B1 (en) 2011-07-22 2018-05-01 The J. David Gladstone Institutes Treatment of HIV-1 infection and AIDS
WO2013052803A2 (en) 2011-10-07 2013-04-11 Radiorx, Inc. Methods and compositions comprising a nitrite-reductase promoter for treatment of medical disorders and preservation of blood products
US9987270B1 (en) 2015-10-29 2018-06-05 Epicentrix, Inc. Treatment of gliomas using organonitro compound combination therapy
CA3011103A1 (en) 2016-01-11 2017-07-20 Epicentrx, Inc. Compositions and methods for intravenous administration of 2-bromo-1-(3,3-dinitroazetidin-1-yl)ethanone
CA3040479A1 (en) * 2016-10-14 2018-04-19 Epicentrx, Inc. Sulfoxyalkyl organonitro and related compounds and pharmaceutical compositions for use in medicine
MX2020000265A (es) 2017-07-07 2020-07-22 Epicentrx Inc Composiciones para la administración parenteral de agentes terapéuticos.
US11510901B2 (en) 2018-01-08 2022-11-29 Epicentrx, Inc. Methods and compositions utilizing RRx-001 combination therapy for radioprotection
CN108997155A (zh) * 2018-09-17 2018-12-14 吉尔生化（上海）有限公司 一种多肽原料天冬氨酸β-叔丁酯α-甲酯盐酸盐的制备方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0618223A3 (en) * 1993-03-08 1996-06-12 Sandoz Ltd Peptides, the release of Interleukin 1-Bêta, useful as anti-inflammatory agents.
TW494094B (en) * 1993-04-29 2002-07-11 Vertex Pharma Peptide analogs as irreversible interleukin-1β protease inhibitors and pharmaceutical compositions comprising the same

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