WO2002002516A3 - Inhibitors of hiv integrase - Google Patents

Inhibitors of hiv integrase Download PDF

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Publication number
WO2002002516A3
WO2002002516A3 PCT/US2001/019923 US0119923W WO0202516A3 WO 2002002516 A3 WO2002002516 A3 WO 2002002516A3 US 0119923 W US0119923 W US 0119923W WO 0202516 A3 WO0202516 A3 WO 0202516A3
Authority
WO
WIPO (PCT)
Prior art keywords
inhibitors
integrase
present invention
hiv integrase
effective
Prior art date
Application number
PCT/US2001/019923
Other languages
French (fr)
Other versions
WO2002002516A2 (en
Inventor
Robert W Harrison
Anna Marie Skalka
Original Assignee
Univ Jefferson
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 to US21547400P priority Critical
Priority to US60/215,474 priority
Application filed by Univ Jefferson filed Critical Univ Jefferson
Publication of WO2002002516A2 publication Critical patent/WO2002002516A2/en
Publication of WO2002002516A3 publication Critical patent/WO2002002516A3/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C225/00Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
    • C07C225/24Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones the carbon skeleton containing carbon atoms of quinone rings
    • C07C225/26Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones the carbon skeleton containing carbon atoms of quinone rings having amino groups bound to carbon atoms of quinone rings or of condensed ring systems containing quinone rings
    • C07C225/32Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones the carbon skeleton containing carbon atoms of quinone rings having amino groups bound to carbon atoms of quinone rings or of condensed ring systems containing quinone rings of condensed quinone ring systems formed by at least three rings
    • C07C225/34Amino anthraquinones
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/52Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C07C229/54Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C07C229/60Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring with amino and carboxyl groups bound in meta- or para- positions
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C257/00Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
    • C07C257/10Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
    • C07C257/18Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36Radicals substituted by singly-bound nitrogen atoms
    • C07D213/38Radicals substituted by singly-bound nitrogen atoms having only hydrogen, hydrocarbon radicals attached to the substituent nitrogen atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D215/00Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen 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
    • C07D215/38Nitrogen atoms

Abstract

The present invention is a series of novel and effective inhibitors of integrase, an essential in the life cycle of retroviruses. These compounds were designed to have a restricted conformation for the determination of the integrase binding site and mechanism of inhibition. The integrase inhibitors of the present invention are effective in the submicromolar range, and thereby provide novel lead compounds for the development of anti-viral therapeutics.
PCT/US2001/019923 2000-06-30 2001-06-22 Inhibitors of hiv integrase WO2002002516A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US21547400P true 2000-06-30 2000-06-30
US60/215,474 2000-06-30

Publications (2)

Publication Number Publication Date
WO2002002516A2 WO2002002516A2 (en) 2002-01-10
WO2002002516A3 true WO2002002516A3 (en) 2002-10-24

Family

ID=22803123

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/019923 WO2002002516A2 (en) 2000-06-30 2001-06-22 Inhibitors of hiv integrase

Country Status (1)

Country Link
WO (1) WO2002002516A2 (en)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1420773A1 (en) * 2001-08-31 2004-05-26 Robert J. Chalifour Amidine derivatives for treating amyloidosis
PA8586801A1 (en) * 2002-10-31 2005-02-04 Pfizer Inhibitors of HIV-integrase, pharmaceutical compositions and methods for use
US7262223B2 (en) 2004-01-23 2007-08-28 Neurochem (International) Limited Amidine derivatives for treating amyloidosis
AT374775T (en) 2004-04-26 2007-10-15 Pfizer Inhibitors of the HIV integrase enzyme
BRPI0510319A (en) 2004-04-26 2007-10-16 Pfizer inhibitors of the HIV integrase
US8008312B2 (en) 2005-01-07 2011-08-30 Emory University CXCR4 antagonists for the treatment of HIV infection
KR20070115879A (en) * 2005-01-07 2007-12-06 에모리 유니버시티 Cxcr4 antagonists for the treatment of medical disorders
EP2041067A4 (en) * 2006-07-11 2009-11-25 Univ Emory Cxer4 antagonists including diazine and triazine structures for the treatment of medical disorders
WO2011007038A2 (en) * 2009-07-15 2011-01-20 Universidade De Santiago De Compostela Use of compounds derived from bis-benzamidines as fluorogenic agents for signalling specific sequencecs of double-strand dna, and novel compounds
ES2351652B1 (en) * 2009-07-15 2011-12-05 Universidade De Santiago De Compostela Use of compounds derived from bis-benzamidios as fluorogenic agents for signaling specific DNA sequences double-stranded.
ES2355031B2 (en) * 2009-07-15 2011-12-26 Universidade De Santiago De Compostela Bis-benzamidinios derivatives and their use as recognition sequences of DNA.
ES2368276B2 (en) * 2010-04-27 2012-06-28 Universidad De Santiago De Compostela bis-derivatives as fluorogenic agents benzamidinios specific signal sequences dsDNA.

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1931122A1 (en) * 1968-06-20 1970-02-12 Fuji Photo Film Co Ltd Color developer composition and process for color reversal development of a photographic multicolor multilayer element
EP0672727A2 (en) * 1994-03-14 1995-09-20 Ciba-Geigy Ag Anthraquinone dyes, process for their preparation and the use thereof
WO1998038170A1 (en) * 1997-02-28 1998-09-03 The University Of North Carolina At Chapel Hill Substituted benzimidazoles and their use for treating retroviral infection
WO1998050347A1 (en) * 1997-05-05 1998-11-12 The Regents Of The University Of California Naphthols useful in antiviral methods
WO1999025327A2 (en) * 1997-11-14 1999-05-27 Warner-Lambert Company Small molecule intervention in hiv-1 replication
WO1999048371A1 (en) * 1998-03-27 1999-09-30 The Regents Of The University Of California Novel hiv integrase inhibitors and hiv therapy based on drug combinations including integrase inhibitors

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1931122A1 (en) * 1968-06-20 1970-02-12 Fuji Photo Film Co Ltd Color developer composition and process for color reversal development of a photographic multicolor multilayer element
EP0672727A2 (en) * 1994-03-14 1995-09-20 Ciba-Geigy Ag Anthraquinone dyes, process for their preparation and the use thereof
WO1998038170A1 (en) * 1997-02-28 1998-09-03 The University Of North Carolina At Chapel Hill Substituted benzimidazoles and their use for treating retroviral infection
WO1998050347A1 (en) * 1997-05-05 1998-11-12 The Regents Of The University Of California Naphthols useful in antiviral methods
WO1999025327A2 (en) * 1997-11-14 1999-05-27 Warner-Lambert Company Small molecule intervention in hiv-1 replication
WO1999048371A1 (en) * 1998-03-27 1999-09-30 The Regents Of The University Of California Novel hiv integrase inhibitors and hiv therapy based on drug combinations including integrase inhibitors

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
HE ZHAO ET AL., J. MED. CHEM., vol. 40, 1997, pages 1186 - 1194, XP000926749 *
HE ZHAO ET AL: "COUMARIN BASED INHIBITORS OF HIV INTEGRASE", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 40, no. 2, 1997, pages 242 - 249, XP002092069, ISSN: 0022-2623 *
KING, P. J. ET AL: "STRUCTURE-ACTIVITY RELATIONSHIPS: ANALOGUES OF THE DICAFFEOYLQUINICAND DICAFFEOYLTARTARIC ACIDS AS POTEN INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 INTEGRASE AND REPLICATION", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 42, no. 3, 1999, pages 497 - 509, XP000919203, ISSN: 0022-2623 *

Also Published As

Publication number Publication date
WO2002002516A2 (en) 2002-01-10

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