KR950702970A - 사람 면역결필 바이러스(HIV) 역전사효소의 억제제로서의 벤족사지논(Benzoxazinones as inhibitors of HIV reverse transcriptase) - Google Patents
사람 면역결필 바이러스(HIV) 역전사효소의 억제제로서의 벤족사지논(Benzoxazinones as inhibitors of HIV reverse transcriptase) Download PDFInfo
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Abstract
본 발명은, 기타 항 바이러스제, 면역조절제, 항생제 또는 백신과의 배합물이거나 또는 아니든지 간에, 화합물, 약제학적으로 허용되는 염 및 약제학적 조성물 성분중 어느 하나로서, HIV 역전사효소(이의 내성 변이체를 포함한)의 억제, HIV에 의한 감염의 예방 또는 치료 및 AIDS의 치료에 유용한 일반식(I)의 특정 벤조사지논에 관한 것이다.
상기식에서, X는 할로이고, X1은 트리할로메틸이거나 펜타할로에틸이고, Z는 0이다. 본 발명은 또한 AIDS치료 방법 및 HIV에 의한 감염의 예방 또는 치료 방법에 관한 것이다.
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
Claims (12)
- 일반식(I)의 화합물 또는 약제학적으로 허용되는 이의 염.상기식에서, X는 할로이고, X1은 트리할로메틸 또는 펜타할로에틸이며, Z는 0이고; R은 (a) 비치환되거나 A에 의해 치환된 C1-8알킬(여기서는, A는 할로, C3-8사이클로알킬, CN, 하이드록시, C1-4알콕시, C2-4알키닐-C1-4알콕시, 아릴옥시, C1-4알킬카보닐, 니트로, 디(C1-2알킬) 아미노, C1-4알킬아미노-C1-2알킬, 헤테로사이클 또는 아킬티오이다) 이거나; (b) 비치환되거나 (i) A 또는 (ii) 비치환되거나 또는 A에 의해 치환된 아릴에 의해 치환된 C2-4알케닐이거나; (c) 비치환되거나 (i) A 또는 (ii) 비치환되거나 또는 A에 의해 치환된 아릴에 의해 치환된 C2-5아키닐이거나; 또는 (d) 비치환되거나 (i) A 또는 (ii) 비치환되거나 또는 A에 의해 치환된 아릴에 의해 치환된 C3-4사이클로 알킬이다.
- 유효량의 일반식(II)의 화합물 또는 약제학적으로 허용되는 이의 염 및 약제학적으로 허용되는 담체를 포함하는, HIV 역전사를 억제하는데 유용한 약제학적 조성물.상기식에서, X는 할로이고, X1은 트리할로메틸; 펜타할로에틸; C2-5알킬; C2-5알키닐; C3-5사이클로알킬 또는 아릴이며, Z는 0 또는 S이고; R은 (a) 비치환되거나 A에 의해 치환된 C1-8알킬(여기에서, A는 할로, C3-6사이클로알킬, CN, 하이드록시, C1-4알콕시, C2-4알키닐 -C1-4알콕시, 아릴옥시, C1-4알킬카보닐, 니트로, 디(C1-2알킬)아미노, C1-4알킬아미노-C1-2알킬, 헤테로사이클 또는 아릴티오이다) 이거나; (b) 비치환되거나 (i) A 또는 (ii) 비치환되거나 또는 A에 의해 치환된 아릴에 의해 치환된 C2-4, 알케닐이거나; (c) 비치환되거나 (i) A 또는 (ii) 비치환되거나 또는 A에 의해 치환된 아릴에 의해 치환된 C2-5알키닐이거나; 또는 (d) 비치환되거나 (i) A 또는 (ii) 비치환되거나 또는 A에 의해 치환된 아릴에 의해 치환된 C3-4사이클로알킬이다.
- (-) 6-클로로-4-사이클로프로필에티닐-4-트리플루오로메틸-1,4-디하이드로-2H-3,1-벤족사진-2-온, (-) 6-클로로-4-페닐에티닐-4-트리플루오로메틸-1,4-디하이드로-2H-3,1-벤족사진-2-온 (+/-) 6-클로로-4-(2-시아노페닐)에티닐-4-(1,1,1-트리플루오로메틸)-1,4-디하이드로-2H-3,1-벤족사진-2-온, (+/-)4-(1-클로로-1,1-디플루오로메틸)-4-(2-페닐에티닐)-6-클로로-1,4-디하이드로-2H-3,1-벤족사진-2-온 또는 (+/-) 4-(2-[디메틸아미노메틸]에티닐)-4-트리플루오로메틸-6-클로로-1,4-디하이드로-2H-3,1-벤족사진-2-온인 화합물, 또는 약제학적으로 허용되는 이의 염.
- 포유동물에게 유효량의 일반식(I) 또는 (II)의 화합물 또는 제3항에 따른 화합물을 투여함을 포함하여, HIV 역전사효소를 억제시키는 방법.
- 포유동물에게 유효량의 일반식(I) 또는 (II)의 화합물 또는 제3항에 따른 화합물을 투여함을 포함하여, HIV의 감염을 예방하거나, HIV에 의한 감염을 치료하거나, 또는 AIDS 또는 ARC를 치료하는 방법.
- 유효량의 제1항, 제2항 또는 제3항에 따른 화합물 및 약제학적으로 허용되는 담체를 포함하는, HIV 역전사효소를 억제시키는데 유용한 약제학적 조성물.
- 유효량의 일반식(I) 또는 일반식(II)의 화합물 또는 제3항에 따른 화합물 및 약제학적으로 허용되는 담체를 포함하는 HIV 감염의 예방 또는 치료, 또는 AIDS 또는 ARC의 치료에 유용한 약제학적 조성물.
- HIV 역전사효소에 대해 생물학적활성을 갖는 뉴클레오사이드 동족체와 일반식(I) 또는 일반식(II)의 화합물의 배합물.
- L-743,726 및 L-735,524인 AIDS 항바이러스 화합물과 임의로, L-697,661, AZT, ddI 또는 ddC로 구성된 그룹으로부터 선택된 하나 이상의 HIV 억제제로 구성된 상승작용성 배합물.
- L-743,726인 AIDS 항바이러스 화합물과 L-697,661, AZT, ddI 또는 ddC로 구성된 그룹으로부터 선택된 하나 이상의 HIV 억제제로 구성된 상승작용성 배합물.
- (a) 일정량의 (+/-)-6-클로로-4-사이클로플필에티닐-4-트리플루오로메틸-1,4-디하이드로-2H-3,1-벤족사진-2-온(L-741,211)을 제공하는 단계; (b) 단계(a)의 화합물을 분해제와 축합시키는 단계; (c) 생성된 부분입체이성체를 분리시키는 단계; 및 (d) 분해제 개질물을 제거하여 목적하는 화합물을 수득하는 단계들을 포함하여, (-)-6-클로로-4-사이클로프로필에티닐-4-트리플루오로메틸-1,4-디하이드로-2H-3,1-벤족사진-2-온(L-743,726)을 합성하는 방법.
- 제11항에 있어서, 분해제가 (-)-캄파닐 클로라이드인 방법.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US92660792A | 1992-08-07 | 1992-08-07 | |
US7/926607 | 1992-08-07 | ||
US07/926,607 | 1992-08-07 | ||
US5480593A | 1993-04-27 | 1993-04-27 | |
US8/054,805 | 1993-04-27 | ||
US08/054,805 | 1993-04-27 | ||
PCT/US1993/007376 WO1994003440A1 (en) | 1992-08-07 | 1993-08-06 | Benzoxazinones as inhibitors of hiv reverse transcriptase |
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KR950702970A true KR950702970A (ko) | 1995-08-23 |
KR100272387B1 KR100272387B1 (ko) | 2000-11-15 |
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KR1019950700472A KR100272387B1 (ko) | 1992-08-07 | 1993-08-06 | 벤족사지논 화합물 및 이를 포함하는 사람 면역결핍 바이러스 역전사 효소 억제용 약제학적 조성물 |
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EP (1) | EP0582455B1 (ko) |
JP (1) | JPH0780860B2 (ko) |
KR (1) | KR100272387B1 (ko) |
CN (3) | CN1318031C (ko) |
AT (1) | ATE197295T1 (ko) |
AU (1) | AU670300B2 (ko) |
BG (1) | BG62612B1 (ko) |
CA (1) | CA2101572C (ko) |
CZ (1) | CZ290447B6 (ko) |
DE (4) | DE10199013I1 (ko) |
DK (1) | DK0582455T3 (ko) |
DZ (1) | DZ1707A1 (ko) |
ES (1) | ES2151897T3 (ko) |
FI (1) | FI115457B (ko) |
GR (1) | GR3034754T3 (ko) |
HK (1) | HK1009267A1 (ko) |
HR (1) | HRP931102B1 (ko) |
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NO (3) | NO304886B1 (ko) |
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RU (1) | RU2186775C2 (ko) |
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UA (1) | UA42699C2 (ko) |
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PL197740B1 (pl) * | 1997-02-05 | 2008-04-30 | Merck & Co Inc | Postać krystaliczna I (-)-6-chloro-4-cyklopropyloetynylo-4-trifluorometylo-1,4-dihydro-2H-3,1-benzoksazyn-2-onu i sposób krystalizacji postaci I (-)-6-chloro-4-cyklopropylo-etynylo-4-trifluorometylo-1,4-dihydro-2H-3,1-benzoksazyn-2-onu |
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JP4157272B2 (ja) * | 1997-09-03 | 2008-10-01 | メルク エンド カムパニー インコーポレーテッド | 2r−[1−ヒドロキシ−1−トリフルオロメチル−3−シクロプロピルプロピン−2−イル]−4−クロロアニリンの光学純度を高める方法 |
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EP1091939A1 (en) * | 1998-06-30 | 2001-04-18 | Du Pont Pharmaceuticals Company | Substituted quinolin-2(1h)-ones useful as hiv reverse transcriptase inhibitors |
SE9904652D0 (sv) * | 1999-12-17 | 1999-12-17 | Astra Pharma Prod | Novel Compounds |
UA73119C2 (en) | 2000-04-19 | 2005-06-15 | American Home Products Corpoir | Derivatives of cyclic thiocarbamates, pharmaceutical composition including noted derivatives of cyclic thiocarbamates and active ingredients of medicines as modulators of progesterone receptors |
WO2002081456A1 (en) | 2001-03-28 | 2002-10-17 | Bristol-Myers Squibb Company | Cyanamide, alkoxyamino, and urea derivatives of 4, 4-disubstituted-3, 4-dihydro-2 (1h)- quinazolinones as hiv reverse transcriptase inhibitors |
EP1608629A1 (en) | 2003-03-24 | 2005-12-28 | F. Hoffmann-La Roche Ag | Benzyl-pyridazinons as reverse transcriptase inhibitors |
ES2549084T3 (es) * | 2007-10-05 | 2015-10-22 | Msd K.K. | Derivados de benzoxazinona |
GB0720503D0 (en) | 2007-10-22 | 2007-11-28 | Angeletti P Ist Richerche Bio | New compound |
EP2448917A2 (de) | 2009-07-03 | 2012-05-09 | Archimica GmbH | Verfahren zur enantioselektiven addition von organometallischen kohlenstoffnukleophilen an trifluormethylketone und verwendung des verfahrens in der synthese von hiv reverse transcriptase inhibitoren |
KR20170078868A (ko) | 2010-01-27 | 2017-07-07 | 비이브 헬쓰케어 컴퍼니 | 항바이러스 치료 |
EP2471783A1 (en) | 2010-12-23 | 2012-07-04 | Esteve Química, S.A. | Novel polymorphic form of efavirenz |
CN103664816B (zh) * | 2011-01-06 | 2016-03-02 | 中国科学院上海有机化学研究所 | Hiv逆转录酶抑制剂依法韦伦类化合物的一锅法不对称合成工艺 |
CN102675125B (zh) * | 2011-03-15 | 2015-02-18 | 中国科学院上海有机化学研究所 | 一种4-氯-2-三氟乙酰基苯胺及其类似物的简便高效合成方法 |
JP7071036B2 (ja) | 2019-02-15 | 2022-05-18 | 福建永晶科技股▲ふん▼有限公司 | Friedel-Crafts反応の新しい新方法及び当該方法に用いられる触媒 |
CN110372625B (zh) * | 2019-08-06 | 2022-11-01 | 常州大学 | 蓝光照射制备4-烷甲基-4-芳基-1,3-苯并噁嗪-2(4h)-酮的方法 |
CN113106473B (zh) * | 2021-04-14 | 2022-02-18 | 南京工业大学 | 一种通过连续电化学微反应器装置制备1,3-苯并噁嗪衍生物的方法 |
WO2023064196A1 (en) * | 2021-10-15 | 2023-04-20 | Merck Sharp & Dohme Llc | Benzoxazinone derivatives as selective cytotoxic agents |
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US3526621A (en) * | 1966-08-03 | 1970-09-01 | Farmaceutical Italia Soc | Substituted 3,1-benzoxazin-2-one |
US3562621A (en) * | 1967-07-26 | 1971-02-09 | Technipower Inc | Inrush current limiting circuit for rectifier circuits with capacitive load |
DE3217012A1 (de) * | 1982-05-06 | 1983-11-10 | Dr. Karl Thomae Gmbh, 7950 Biberach | Benzoxazin-2-one, deren herstellung und diese verbindungen enthaltende arzneimittel |
CA2032259A1 (en) * | 1989-12-18 | 1991-06-19 | Wayne J. Thompson | Hiv protease inhibitors useful for the treatment of aids |
IL99843A0 (en) * | 1990-11-01 | 1992-08-18 | Merck & Co Inc | Synergistic combination of hiv reverse transcriptase inhibitors |
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