KR940014337A - 에이즈의 치료에 유용한 에이치아이브이(hiv) 프로테아제 억제제 - Google Patents

에이즈의 치료에 유용한 에이치아이브이(hiv) 프로테아제 억제제 Download PDF

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Publication number
KR940014337A
KR940014337A KR1019930029121A KR930029121A KR940014337A KR 940014337 A KR940014337 A KR 940014337A KR 1019930029121 A KR1019930029121 A KR 1019930029121A KR 930029121 A KR930029121 A KR 930029121A KR 940014337 A KR940014337 A KR 940014337A
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South Korea
Prior art keywords
alkyl
heterocycle
aryl
hydroxy
pharmaceutically acceptable
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KR1019930029121A
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English (en)
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니콜라우스 정하임 루이스
알란 셰퍼드 티모시
Original Assignee
피터 지. 스트링거
일라이 릴리 앤드 캄파니
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Priority claimed from US08/134,329 external-priority patent/US5733906A/en
Application filed by 피터 지. 스트링거, 일라이 릴리 앤드 캄파니 filed Critical 피터 지. 스트링거
Publication of KR940014337A publication Critical patent/KR940014337A/ko

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/58—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems with hetero atoms directly attached to the ring nitrogen atom
    • C07D215/60—N-oxides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
    • C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Abstract

본 발명은 신규 HIV 프로테아제 억제제, 이러한 화합물을 함유한 약학적 제형, 및 HIV 감염 및/또는 AIDS의 치료 및/또는 예방법을 제공한다.

Description

에이즈의 치료에 유용한 에이치아이브이(HIV) 프로테아제 억제제
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (4)

  1. 하기 일반식(Ⅰ)의 화합물 또는 그의 약학적으로 허용가능한 염 :
    상기식에서, R은 하기 일반식을 갖는 그룹이고 ;
    R2는 아미노산 측쇄 또는 -(CH2)y-X-R2a이고 ; y는 0, 1 또는 2이고 ; X는 결합, 이가(C2내지 C4)알케닐, 이가(C2내지 C4)알키닐, -C(O)-O-, -0-C(O)-, -C(O)-NR2b-, NR2b-C(O)-, -NR2b-, -C(O)-, -O-, -S-, -S(O)- 또는 -S(O)2- 이고 ; R2a는 아릴, 불포화 헤테로사이클, 헤테로사이클, 아릴(C1, 내지 C4)알킬, 불포화 헤테로사이클(C1내지 C4)알킬, 헤테로사이클(C1내지 C4)알킬, 테트라졸릴, N-(C1내지 C4)알킬테트라졸릴 또는 N-(아릴)테트라졸릴이고 ; R2b는 수소 또는 C1내지 C4알킬이고 ; R0는 수소, 카바모일, 포르밀, C2내지 C6알카노일, C1내지 C4알콕시카보닐, -C(O)CF3또는 -S(O)2-Z 이고 ; Z는 C1 내지 C6알킬, 아미노, C1내지 C4알킬아미노, 트리플루오로메틸 또는 디(C1내지 C4)알킬아미노이고; 비대칭 탄소 σ는 자연 발생적이 아닌 형태이고 ; R1는 아릴, C5내지 C7사이클로알킬 또는 -S-R1x(이때, R1x는 아릴 또는 C5내지 C7사이클로알킬이다)이고 ; A는 -CH2-또는이고 ; Y1은 헤테로사이클이고 ; R3은
    p는 4 또는 5이고 ; R4는 각각의 경우 독립적으로, 수소, C1내지 C6알킬 또는 하이드록시(C1내지 C4)알킬이고 ; R5및 R6은 독립적으로 수소, 하이드록시, C1내지 C6알킬, C1내지 C6알콕시, 아미노, C1내지 C4알킬아미노, 하이드록시(C1내지 C4)-알킬, 카복시, C1내지 C4알콕시카보닐, 카바모일, N-(C1내지 C4)알킬카바모일, 아릴, 헤테로사이클 또는 불포화 헤테로사이클 중에서 선택된다.
  2. 제 1 항에 있어서, R1a, Y1, R5또는 R6중 어느 하나가 헤테로사이클일 때, 헤테로사이클이 -(CH2)4-피리딜로 치환될 수 없는 화합물 또는 그의 약학적으로 허용되는 염.
  3. [2R-(2R*, 3S*, 6S*, 3'S*, 4a'S*, 8a'S*)]-N-(t-부틸)-2′-[2-하이드록시-3-페닐메틸-4-아자-5-옥소-6-N(메틸설포닐)-아미노-7-p-플루오로-페닐셜포닐]헵틸 데카하이드로이소퀴놀린-3'-카복스아미드 메탄설포네이트 ; 또는 [2R-(2R*, 3S*, 6S*, 3'S*, 4a'S*, 8a'S*)]-N-(t-부틸)-2′-[2-하이드록시-3-페닐메틸-4-아자-5-옥소-6-N(메틸설포닐9 아미노-7-나프트-2-일설포닐]헵틸 데카하이드로이소퀴놀린-3′-카복스아미드 또는 그의 약학적으로 허용되는 염.
  4. 제 1 내지 3항 중 어느 한 항에 청구된 일반식(Ⅰ)의 화합물 또는 그의 약학적으로 허용되는 염을 그에 대한 하나 이상의 약학적으로 허용되는 담체, 부형제 또는 희석제와 함께 포함하는 약학제제.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019930029121A 1992-12-22 1993-12-22 에이즈의 치료에 유용한 에이치아이브이(hiv) 프로테아제 억제제 KR940014337A (ko)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US99525692A 1992-12-22 1992-12-22
US7/995,256 1992-12-22
US08/134,329 US5733906A (en) 1993-10-12 1993-10-12 Inhibitors of HIV Protease useful for the treatment of Aids
US8/134,329 1993-10-12

Publications (1)

Publication Number Publication Date
KR940014337A true KR940014337A (ko) 1994-07-18

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ID=26832220

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Country Status (21)

Country Link
US (1) US5905077A (ko)
EP (1) EP0604185B1 (ko)
JP (1) JPH06271534A (ko)
KR (1) KR940014337A (ko)
CN (1) CN1044117C (ko)
AT (1) ATE178055T1 (ko)
AU (1) AU667146B2 (ko)
BR (1) BR9305162A (ko)
CA (1) CA2112042A1 (ko)
CZ (1) CZ281493A3 (ko)
DE (1) DE69324120T2 (ko)
ES (1) ES2132201T3 (ko)
FI (1) FI935778A (ko)
HU (1) HUT69693A (ko)
IL (1) IL108092A (ko)
MX (1) MX9308016A (ko)
MY (1) MY131388A (ko)
NO (1) NO934719L (ko)
NZ (1) NZ250491A (ko)
PL (1) PL301581A1 (ko)
TW (1) TW262468B (ko)

Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
USH1649H (en) 1987-07-31 1997-05-06 Barrish; Joel C. HIV protease inhibitor combinations
US6071895A (en) 1992-03-11 2000-06-06 Narhex Limited Polar-substituted hydrocarbons
RU2126794C1 (ru) 1992-03-11 1999-02-27 Нархекс Лимитед Аминопроизводные оксо- или гидроксизамещенных гидразинов, способ их получения и фармацевтические композиции для ингибирования ретровирусной протеазы
US5888992A (en) 1992-03-11 1999-03-30 Narhex Limited Polar substituted hydrocarbons
US5484926A (en) 1993-10-07 1996-01-16 Agouron Pharmaceuticals, Inc. HIV protease inhibitors
US5461154A (en) * 1994-02-02 1995-10-24 Eli Lilly And Company Intermediate and process for making
TW472047B (en) * 1994-02-04 2002-01-11 Merck & Co Inc Process for making HIV protease inhibitors
ATE163642T1 (de) * 1994-11-04 1998-03-15 Yamakawa Chemical Ind Verfahren zur herstellung von optisch aktiven piperazinderivaten und zwischenprodukten für ihre herstellung
ES2167541T3 (es) * 1995-02-03 2002-05-16 Kaneka Corp Procedimientos de produccion de alfa-halocetonas, de alfa-halohidrinas y de epoxidos.
US5618937A (en) * 1995-03-15 1997-04-08 Merck & Co., Inc. Process to make HIV protease inhibitor from (2S)-4-picolyl-2-piperazine-t-butylcarboxamide
US6222043B1 (en) 1995-06-30 2001-04-24 Japan Energy Corporation Methods of preparing novel dipeptide compounds or pharmaceutically acceptable salts thereof
US5932550A (en) * 1995-06-30 1999-08-03 Japan Energy Corporation Dipeptide compound or pharmaceutically acceptable salt thereof and medical use thereof
PT983999E (pt) * 1995-09-26 2005-05-31 Agouron Pharma Processo para a producao de derivados amida e dos seus intermediarios
JP3611332B2 (ja) * 1995-09-26 2005-01-19 日本たばこ産業株式会社 アミド誘導体の製造方法及び中間体化合物
ES2293651T3 (es) * 1995-11-28 2008-03-16 Cephalon, Inc. Inhibidores de cisteina y serina proteasas derivados de aminoacidos d.
US5962725A (en) 1996-09-05 1999-10-05 Agouron Pharmaceuticals, Inc. Intermediate compounds useful for making HIV protease inhibitors such as nelfinavir
CA2249747A1 (en) 1996-12-27 1998-07-09 Tsutomu Mimoto Novel tripeptide compounds and anti-aids drugs
JP4006058B2 (ja) 1997-03-11 2007-11-14 第一三共株式会社 多臓器不全予防及び／又は治療剤
DK0950416T3 (da) 1997-03-14 2007-02-26 Daiichi Seiyaku Co Anvendelse af TCF-II til behandling af cancerrelateret tab af kropsvægt, anæmi og TNF-forhöjelse
US6538006B1 (en) * 1998-07-08 2003-03-25 Pharmacia Corporation Retroviral protease inhibitors
NZ525513A (en) 1998-08-07 2004-09-24 Pont Pharmaceuticals Du Succinoylamino lactams as inhibitors of Abeta protein production
HRP990246A2 (en) * 1998-08-07 2000-06-30 Du Pont Pharm Co Succinoylamino benzodiazepines as inhibitors of a beta protein production
BR9917082A (pt) * 1998-12-24 2001-11-06 Du Pont Pharm Co Compostos inibidores da produção de proteìnas a"beta", método de tratamento de disfunções neurológicas associadas com a produção de "beta"-amilóide, composição farmacêutica e, método de inibição da atividade de y-secretase
US6960576B2 (en) 1999-09-13 2005-11-01 Bristol-Myers Squibb Pharma Company Hydroxyalkanoylaminolactams and related structures as inhibitors of Aβ protein production
US6503902B2 (en) 1999-09-13 2003-01-07 Bristol-Myers Squibb Pharma Company Hydroxyalkanoylaminolactams and related structures as inhibitors of a β protein production
US6503901B1 (en) 1999-10-08 2003-01-07 Bristol Myers Squibb Pharma Company Amino lactam sulfonamides as inhibitors of Aβ protein production
JP2003523345A (ja) 2000-02-17 2003-08-05 ブリストル−マイヤーズ スクイブ ファーマ カンパニー Ａβタンパク質産生の阻害剤としてのスクシノイルアミノ炭素環および複素環
US6495540B2 (en) 2000-03-28 2002-12-17 Bristol - Myers Squibb Pharma Company Lactams as inhibitors of A-β protein production
MXPA02009729A (es) 2000-04-03 2003-03-27 Bristol Myers Squibb Pharma Co Lactamas ciclicas como inhibidores de la produccion de la proteina a-beta.
CN1436175A (zh) 2000-04-03 2003-08-13 布里斯托尔-迈尔斯斯奎布药品公司 作为Aβ－蛋白生产抑制剂的环状内酰胺
US20100009966A1 (en) * 2001-04-11 2010-01-14 Bristol-Myers Squibb Pharma Company Substituted lactams as inhibitors of abeta protein production
WO2001077086A1 (en) * 2000-04-11 2001-10-18 Dupont Pharmaceuticals Company SUBSTITUTED LACTAMS AS INHIBITORS OF Aβ PROTEIN PRODUCTION
US6878363B2 (en) * 2000-05-17 2005-04-12 Bristol-Myers Squibb Pharma Company Use of small molecule radioligands to discover inhibitors of amyloid-beta peptide production and for diagnostic imaging
WO2001092235A1 (en) 2000-06-01 2001-12-06 Bristol-Myers Squibb Pharma Company LACTAMS SUBSTITUTED BY CYCLIC SUCCINATES AS INHIBITORS OF Aβ PROTEIN PRODUCTION
GB0028483D0 (en) * 2000-11-22 2001-01-10 Hoffmann La Roche Hydroxyethylamine HIV protease inhibitors
JPWO2002064553A1 (ja) * 2001-02-14 2004-06-10 呉羽化学工業株式会社 ハロゲノアルコール誘導体の製造方法
US20090062256A1 (en) * 2001-06-01 2009-03-05 Bristol-Myers Squibb Pharma Company LACTAMS SUBSTITUTED BY CYCLIC SUCCINATES AS INHIBITORS OF Abeta PROTEIN PRODUCTION
GB0123467D0 (en) 2001-09-28 2001-11-21 Hoffmann La Roche Carbocyclic HIV Protease inhibitors
KR101155335B1 (ko) * 2005-01-07 2012-06-11 엘지전자 주식회사 이동통신 단말기의 멀티미디어 메시지 동작방법
ES2426345T3 (es) 2005-07-20 2013-10-22 Eli Lilly And Company Compuesto unidos en posición 1-amino
CN101508664B (zh) * 2009-02-25 2012-08-22 江阴希迪医药科技有限公司 N-苄氧羰基-3-氨基-1-氯-4-苯硫基-2-丁醇合成方法
JP5984218B2 (ja) 2010-07-02 2016-09-06 ギリアード サイエンシーズ， インコーポレイテッド Ａｉｄｓを処置するためのナフト−２−イル酢酸誘導体
US9296758B2 (en) 2010-07-02 2016-03-29 Gilead Sciences, Inc. 2-quinolinyl-acetic acid derivatives as HIV antiviral compounds
US9006229B2 (en) 2011-04-21 2015-04-14 Gilead Sciences, Inc. Benzothiazole compounds and their pharmaceutical use
US9376392B2 (en) 2012-01-04 2016-06-28 Gilead Sciences, Inc. 2-(tert-butoxy)-2-(7-methylquinolin-6-yl) acetic acid derivatives for treating AIDS
WO2013103738A1 (en) 2012-01-04 2013-07-11 Gilead Sciences, Inc. Napthalene acetic acid derivatives against hiv infection
EP3070081B1 (en) 2012-04-20 2018-02-28 Gilead Sciences, Inc. Benzothiazol-6-yl acetic acid derivatives and their use for treating an hiv infection

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5142056A (en) * 1989-05-23 1992-08-25 Abbott Laboratories Retroviral protease inhibiting compounds
IL89900A0 (en) * 1988-04-12 1989-12-15 Merck & Co Inc Hiv protease inhibitors useful for the treatment of aids and pharmaceutical compositions containing them
CA1340588C (en) 1988-06-13 1999-06-08 Balraj Krishan Handa Amino acid derivatives
EP0361341A3 (en) * 1988-09-28 1991-07-03 Miles Inc. Therapeutics for aids based on inhibitors of hiv protease
GB8927913D0 (en) * 1989-12-11 1990-02-14 Hoffmann La Roche Amino acid derivatives
CA2096525C (en) 1990-11-19 2005-02-08 Deborah Elizabeth Bertenshaw Retroviral protease inhibitors
CA2060844A1 (en) * 1991-02-08 1992-08-09 Yabe Yuichiro Beta-amino-alpha-hydroxycarboxylic acids and their use
US5430041A (en) * 1991-05-10 1995-07-04 Hoffmann-La Roche Inc. Amino acid derivatives having antiviral activity
CN1071930A (zh) * 1991-07-10 1993-05-12 伊莱利利公司 用作治疗艾滋病的人免疫缺陷病毒蛋白酶的抑制剂
WO1993013066A1 (en) 1991-12-20 1993-07-08 Syntex (U.S.A.) Inc. Cyclic amides of 3-amino-2-hydroxy-carboxylic acids as hiv-protease inhibitors
US5312820A (en) * 1992-07-17 1994-05-17 Merck & Co., Inc. Substituted carbamoyl and oxycarbonyl derivatives of biphenylmethylamines

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EP0604185A1 (en) 1994-06-29
DE69324120D1 (de) 1999-04-29
DE69324120T2 (de) 1999-11-25
HUT69693A (en) 1995-09-28
IL108092A (en) 1998-06-15
CZ281493A3 (en) 1994-07-13
AU5252893A (en) 1994-07-07
NO934719L (no) 1994-06-23
US5905077A (en) 1999-05-18
FI935778A0 (fi) 1993-12-21
CN1044117C (zh) 1999-07-14
EP0604185B1 (en) 1999-03-24
NZ250491A (en) 1995-08-28
AU667146B2 (en) 1996-03-07
JPH06271534A (ja) 1994-09-27
CA2112042A1 (en) 1994-06-23
MX9308016A (es) 1994-08-31
MY131388A (en) 2007-08-30
CN1094399A (zh) 1994-11-02
ATE178055T1 (de) 1999-04-15
ES2132201T3 (es) 1999-08-16
BR9305162A (pt) 1994-11-01
FI935778A (fi) 1994-06-23
TW262468B (ko) 1995-11-11
IL108092A0 (en) 1994-04-12
PL301581A1 (en) 1994-06-27
NO934719D0 (no) 1993-12-20

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