EP1083897A4 - Hiv integrase-inhibitoren - Google Patents

Hiv integrase-inhibitoren

Info

Publication number
EP1083897A4
EP1083897A4 EP99926096A EP99926096A EP1083897A4 EP 1083897 A4 EP1083897 A4 EP 1083897A4 EP 99926096 A EP99926096 A EP 99926096A EP 99926096 A EP99926096 A EP 99926096A EP 1083897 A4 EP1083897 A4 EP 1083897A4
Authority
EP
European Patent Office
Prior art keywords
alkyl
pyrrol
substituted
dioxobutyric acid
independently selected
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP99926096A
Other languages
English (en)
French (fr)
Other versions
EP1083897A1 (de
Inventor
Harold G Selnick
Daria Jean Hazuda
Melissa Egbertson
James P Guare Jr
John S Wai
Steven D Young
David L Clark
Julio C Medina
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck and Co Inc
Tularik Inc
Original Assignee
Merck and Co Inc
Tularik Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GBGB9814930.5A external-priority patent/GB9814930D0/en
Application filed by Merck and Co Inc, Tularik Inc filed Critical Merck and Co Inc
Publication of EP1083897A1 publication Critical patent/EP1083897A1/de
Publication of EP1083897A4 publication Critical patent/EP1083897A4/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/333—Radicals substituted by oxygen or sulfur atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/12—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond

Definitions

  • Integration is believed to be mediated by integrase in three steps: assembly of a stable nucleoprotein complex with viral DNA sequences; cleavage of two nucleotides from the 3' termini of the linear proviral DNA; covalent joining of the recessed 3' OH termini of the proviral DNA at a staggered cut made at the host target site.
  • the fourth step in the process, repair synthesis of the resultant gap may be accomplished by cellular enzymes.
  • Nucleotide sequencing of HIV shows the presence of a pol gene in one open reading frame [Ratner, L. et al., Nature, 313, 277(1985)].
  • R8 is selected from: (1) -H,
  • Step 3 4-[l-(4-fluorobenzyl)-lH-pyrrol-2-yl]-2,4-dioxo-butyric acid

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pyrrole Compounds (AREA)
  • Indole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
EP99926096A 1998-06-03 1999-06-01 Hiv integrase-inhibitoren Withdrawn EP1083897A4 (de)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US8784598P 1998-06-03 1998-06-03
US87845P 1998-06-03
GBGB9814930.5A GB9814930D0 (en) 1998-07-09 1998-07-09 HIV integrase inhibitors
GB9814930 1998-07-09
PCT/US1999/012095 WO1999062513A1 (en) 1998-06-03 1999-06-01 Hiv integrase inhibitors

Publications (2)

Publication Number Publication Date
EP1083897A1 EP1083897A1 (de) 2001-03-21
EP1083897A4 true EP1083897A4 (de) 2003-01-02

Family

ID=26314003

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99926096A Withdrawn EP1083897A4 (de) 1998-06-03 1999-06-01 Hiv integrase-inhibitoren

Country Status (5)

Country Link
EP (1) EP1083897A4 (de)
JP (1) JP2002516858A (de)
AU (1) AU756826C (de)
CA (1) CA2329134A1 (de)
WO (1) WO1999062513A1 (de)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ID26031A (id) 1998-03-26 2000-11-16 Shionogi & Co Turunan indol yang memiliki suatu aktivitas antiviral
JP2003525200A (ja) 1998-07-27 2003-08-26 イスティトゥト ディ リチェルケ ディ ビオロジア モレコラーレ ピー．アンジェレッティ ソチエタ ペル アツィオニ ポリメラーゼ阻害剤としてのジケト酸誘導体
ATE411286T1 (de) 1998-12-25 2008-10-15 Shionogi & Co Aromatische heterocyclen mit hiv integrase inhibierenden eigenschaften
AU5880600A (en) * 1999-06-25 2001-01-31 Merck & Co., Inc. 1-(aromatic- or heteroaromatic-substituted)-3-(heteroaromatic substituted)-1,3-propanediones and uses thereof
JP3616628B2 (ja) 2001-03-01 2005-02-02 塩野義製薬株式会社 Ｈｉｖインテグラーゼ阻害活性を有する含窒素芳香族複素環化合物
BR0211750A (pt) 2001-08-10 2004-10-13 Shionogi & Co Agente antiviral
US7323460B2 (en) 2002-03-15 2008-01-29 Merck & Co., Inc. N-(substituted benzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamides useful as HIV integrase inhibitors
WO2004024693A1 (ja) 2002-08-13 2004-03-25 Shionogi & Co., Ltd. Ｈｉｖインテグラーゼ阻害活性を有するヘテロ環化合物
US20040157804A1 (en) 2002-10-16 2004-08-12 Gilead Sciences, Inc. Pre-organized tricyclic integrase inhibitor compounds
EP1664046B1 (de) 2003-09-19 2009-06-17 Gilead Sciences, Inc. Azachinolinolphosphonatverbindungen als integraseinhibitoren
US7776883B2 (en) 2004-03-10 2010-08-17 The United States Of America As Represented By The Department Of Health And Human Services Quinolin-4-ones as inhibitors of retroviral integrase for the treatment of HIV, AIDS and AIDS related complex (ARC)
US7745459B2 (en) 2004-09-21 2010-06-29 Japan Tobacco Inc. Quinolizinone compound and use thereof as HIV integrase inhibitor
US7741315B2 (en) * 2005-05-10 2010-06-22 Merck Sharp & Dohme Corp. HIV integrase inhibitors
US20090306054A1 (en) 2006-05-16 2009-12-10 Gilead Sciences ,Inc. Integrase inhibitors
JP2009543865A (ja) 2006-07-19 2009-12-10 ユニバーシティ オブ ジョージア リサーチ ファウンデーション， インコーポレーテッド ピリジノンジケト酸：併用療法におけるｈｉｖ複製の阻害剤
ES2572631T3 (es) 2008-01-25 2016-06-01 Chimerix, Inc. Métodos de tratamiento de infecciones virales
US8664255B2 (en) 2008-10-20 2014-03-04 The Texas A&M University System Inhibitors of mycobacterium tuberculosis malate synthase, methods of making and uses thereof
KR20120094098A (ko) 2009-12-07 2012-08-23 유니버시티 오브 조지아 리서치 파운데이션, 인코포레이티드 피리디논 하이드록시사이클로펜틸 카복사미드: 치료 용도의 ｈｉｖ 인테그라제 억제제
US8283366B2 (en) 2010-01-22 2012-10-09 Ambrilia Biopharma, Inc. Derivatives of pyridoxine for inhibiting HIV integrase
DK2534150T3 (en) 2010-02-12 2017-06-12 Chimerix Inc METHODS OF TREATING VIRUS INFECTION
CN103420894A (zh) * 2012-05-22 2013-12-04 中国科学院上海药物研究所 丁-2-烯-1,4-二酮类化合物及其制备方法和用途
KR20220100607A (ko) * 2019-10-28 2022-07-15 상하이 인스티튜트 오브 마테리아 메디카 차이니즈 아카데미 오브 싸이언시즈 5원 헤테로사이클릭 옥소카르복실산 화합물 및 이의 의약 용도

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS554334A (en) * 1978-06-24 1980-01-12 Yoshitomi Pharmaceut Ind Ltd Pyranopyrazole derivative
JPS5535066A (en) * 1978-09-05 1980-03-11 Yoshitomi Pharmaceut Ind Ltd Novel pyrazole derivative
US4386092A (en) * 1980-01-16 1983-05-31 Yoshitomi Pharmaceutical Industries, Ltd. Heterocyclic-substituted oxoalkanoic acid derivatives
JPS61164346A (ja) * 1985-01-17 1986-07-25 Matsushita Electric Ind Co Ltd エコ−キヤンセラ
SU1373708A1 (ru) * 1986-08-04 1988-02-15 Пермский фармацевтический институт Способ получени 5,6-диарил-2-карбокси-4,7-диоксо-5н-пирроло-(3,4-в)пиранов
WO1998018473A1 (en) * 1996-10-31 1998-05-07 Merck & Co., Inc. Benzodiazepine hydrazide derivatives as inhibitors of hiv integrase

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5192773A (en) * 1990-07-02 1993-03-09 Vertex Pharmaceuticals, Inc. Immunosuppressive compounds

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS554334A (en) * 1978-06-24 1980-01-12 Yoshitomi Pharmaceut Ind Ltd Pyranopyrazole derivative
JPS5535066A (en) * 1978-09-05 1980-03-11 Yoshitomi Pharmaceut Ind Ltd Novel pyrazole derivative
US4386092A (en) * 1980-01-16 1983-05-31 Yoshitomi Pharmaceutical Industries, Ltd. Heterocyclic-substituted oxoalkanoic acid derivatives
JPS61164346A (ja) * 1985-01-17 1986-07-25 Matsushita Electric Ind Co Ltd エコ−キヤンセラ
SU1373708A1 (ru) * 1986-08-04 1988-02-15 Пермский фармацевтический институт Способ получени 5,6-диарил-2-карбокси-4,7-диоксо-5н-пирроло-(3,4-в)пиранов
WO1998018473A1 (en) * 1996-10-31 1998-05-07 Merck & Co., Inc. Benzodiazepine hydrazide derivatives as inhibitors of hiv integrase

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
DATABASE CAPLUS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; XP002218136 *
DATABASE CAPLUS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; XP002218137 *
DATABASE CAPLUS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; XP002218138 *
DATABASE CAPLUS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; XP002218139 *
DATABASE CAPLUS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; XP002218140 *
DATABASE CAPLUS CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; XP002218141 *
F. EIDEN ET AL.: "4-Pyrones. 54. 4-Pyrono[2,3-b]pyrroles", ARCHIV DER PHARMAZIE, vol. 308, no. 8, 1975, VCH VERLAGSGESELLSCHAFT MBH, WEINHEIM., DE, pages 598 - 602, ISSN: 0365-6233 *
See also references of WO9962513A1 *
TREFOR(SIC!) T. HOWARD ET AL.: "Pyrroles and related compounds. XXVI. Pyrrole.beta.-keto esters", JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 1, no. 4, 1974, CHEMICAL SOCIETY. LETCHWORTH., GB, pages 490 - 501, ISSN: 0368-1769 *

Also Published As

Publication number Publication date
AU756826C (en) 2003-08-21
WO1999062513A1 (en) 1999-12-09
AU4225699A (en) 1999-12-20
AU756826B2 (en) 2003-01-23
JP2002516858A (ja) 2002-06-11
CA2329134A1 (en) 1999-12-09
EP1083897A1 (de) 2001-03-21

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