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US20120295898A1 - Antiviral Therapy - Google Patents

Antiviral Therapy Download PDF

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US20120295898A1
US20120295898A1 US13/575,380 US201113575380A US2012295898A1 US 20120295898 A1 US20120295898 A1 US 20120295898A1 US 201113575380 A US201113575380 A US 201113575380A US 2012295898 A1 US2012295898 A1 US 2012295898A1
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compound
formula
pharmaceutically acceptable
abacavir
combination
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Mark Richard Underwood
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ViiV Healthcare Co
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Publication of US20120295898A1 publication Critical patent/US20120295898A1/en
Assigned to GLAXOSMITHKLINE LLC reassignment GLAXOSMITHKLINE LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: UNDERWOOD, MARK RICHARD
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    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/536—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with carbocyclic ring systems
    • A—HUMAN NECESSITIES
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    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
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    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
    • A—HUMAN NECESSITIES
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    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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    • A—HUMAN NECESSITIES
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    • A—HUMAN NECESSITIES
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    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2121/00—Preparations for use in therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • HIV human immunodeficiency virus
  • AIDS acquired immunodeficiency syndrome
  • ARC AIDS-related complex
  • HIV is a retrovirus; the conversion of its RNA to DNA is accomplished through the action of the enzyme reverse transcriptase.
  • Compounds that inhibit the function of reverse transcriptase inhibit replication of HIV in infected cells. Such compounds are useful in the prevention or treatment of HIV infection in humans.
  • HIV requires a co-receptor for entry into target cells.
  • the chemokine receptors function together with CD4 as co-receptors for HIV.
  • the chemokine receptors CXCR4 and CCR5 have been identified as the main co-receptors for HIV-1.
  • CCR5 acts as a major co-receptor for fusion and entry of macrophage-tropic HIV into host cells. These chemokine receptors are thought to play an essential role in the establishment and dissemination of an HIV infection. Therefore, CCR5 antagonists are thought to be useful as therapeutic agents active against HIV.
  • HIV encodes the production of a protease which carries out post-translational cleavage of precursor polypeptides in a process necessary for the formation of infectious virions.
  • gene products include pol, which encodes the virion RNA-dependent DNA polymerase (reverse transcriptase), an endonuclease, HIV protease, and gag, which encodes the core-proteins of the virion.
  • anti-viral drug design has been to create compounds which inhibit the formation of infectious virions by interfering with the processing of viral polyprotein precursors. Processing of these precursor proteins requires the action of virus-encoded proteases which are essential for replication. The anti-viral potential of HIV protease inhibition has been demonstrated using peptidyl inhibitors.
  • a required step in HIV replication in human T-cells is the insertion by virally-encoded integrase of proviral DNA into the host cell genome. Integration is believed to be mediated by integrase in a process involving assembly of a stable nucleoprotein complex with viral DNA sequences, cleavage of two nucleotides from the 3′ termini of the linear proviral DNA and covalent joining of the recessed 3′ OH termini of the proviral DNA at a staggered cut made at the host target site. The repair synthesis of the resultant gap may be accomplished by cellular enzymes. Inhibitors of HIV integrase can be effective in treating AIDS and inhibiting viral replication.
  • Combinations administered in a single dosage unit can result in increased patient compliance as the pill burden is reduced and dosing schedules are simplified.
  • Factors that influence the feasibility of combinations include the chemical instability of the compounds, size of the dosage unit, potential for antagonistic or merely additive activities of the combined compounds, and difficulties in achieving a suitable formulation.
  • HIV integrase inhibitors are attractive as components in combination therapy.
  • FIG. 1 Inhibition of HIV-1 IIIB by a compound of formula (I), GSK1349572A, in combination with abacavir (ABC).
  • FIG. 2 Inhibition of HIV-1 IIIB by a compound of formula (I), GSK1349572A, in combination with efavirenz (EFV).
  • FIG. 3 Inhibition of HIV-1 IIIB by a compound of formula (I), GSK1349572A, in combination with lopinavir (LPV)
  • the present invention relates to combinations of compounds comprising HIV integrase inhibitors and other therapeutic agents. Such combinations are useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.
  • the present invention also features pharmaceutical compositions containing HIV integrase inhibitors.
  • the present invention relates to combinations comprising a compound of the following formula (I), (II), or (III):
  • nucleotide reverse transcriptase inhibitors nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, CCR5 antagonists, CXCR4 antagonists, fusion inhibitors, maturation inhibitors, and integrase inhibitors.
  • NRTIs nucleoside reverse transcriptase inhibitors
  • NRTIs non-nucleoside reverse transcriptase inhibitors
  • protease inhibitors CCR5 antagonists
  • CXCR4 antagonists CXCR4 antagonists
  • fusion inhibitors maturation inhibitors
  • maturation inhibitors maturation inhibitors
  • integrase inhibitors integrase inhibitors
  • the present invention relates to methods of treatment of HIV infection, AIDS, and AIDS related conditions by administering to a subject a compound of formula (I), (II), or (III) and one or more therapeutic agents selected from the group consisting of nucleotide reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, CCR5 antagonists, CXCR4 antagonists, fusion inhibitors, maturation inhibitors, and integrase inhibitors.
  • nucleotide reverse transcriptase inhibitors nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs)
  • protease inhibitors CCR5 antagonists, CXCR4 antagonists, fusion inhibitors, maturation inhibitors, and integrase inhibitors.
  • a compound of formula (I) is also known as GSK1349572.
  • a chemical name of the compound of formula (I) is (4R, 12a5)-N-[2,4-flurophenyl)methyl]-3,4,6,8,12,12a-hexahydro-7-hydroxy-4-methyl-6,8-dioxo-2H-pyrido [1′,2′:4,5]pyrazino [2,1-b] [1,3] oxazine-9-carboxamide.
  • a chemical name of the compound of formula (II) is (3S, 11aR)-N-[(2,4-difluorophenyl)methyl]-2,3,5,7,11,11a-hexahydro-6-hydroxy-3-methyl-5,7-dioxo-oxazolo [3,2-a] pyrido [1,2-d] pyrazine-8-carboxamide.
  • a chemical name of the compound of formula (III) is (4aS,13aR)-N-[2,4-difluorophenyl)methyl]-10-hydroxy-9,11-dioxo-2,3,4a,5,9,11,13,13a-octahydro-1H-pyrido [1,2-a]pyrrolo[1′,2′:3,4,]imidazo[1,2-d]pyrazine-8-carboxamide.
  • pharmaceutically acceptable carrier or adjuvant refers to a carrier or adjuvant that may be administered to a patient, together with a compound of this invention, and which does not destroy the pharmacological activity thereof and is nontoxic when administered in doses sufficient to deliver a therapeutic amount of the antiviral agent.
  • treatment refers to the alleviation of symptoms of a particular disorder in a patient, or the improvement of an ascertainable measurement associated with a particular disorder, and may include the suppression of symptom recurrence in an asymptomatic patient such as a patient in whom a viral infection has become latent. Treatment may include prophylaxis which refers to preventing a disease or condition or preventing the occurrence of symptoms of such a disease or condition, in a patient.
  • patient refers to a mammal, including a human.
  • the term “subject” refers to a patient, animal or a biological sample.
  • Pharmaceutically acceptable salts of the compounds according to the invention include those derived from pharmaceutically acceptable inorganic and organic acids and bases.
  • suitable acids include hydrochloric, hydrobromic, sulfuric, nitric, perchloric, fumaric, maleic, phosphoric, glycollic, lactic, salicyclic, succinic, toluene-p-sulfonic, tartaric, acetic, citric, methanesulfonic, ethanesulfonic, formic, benzoic, malonic, naphthalene-2-sulfonic and benzenesulfonic acids.
  • Salts derived from appropriate bases include alkali metal (e.g. sodium), alkaline earth metal (e.g., magnesium), ammonium, NW 4 + (wherein W is C 1-4 alkyl) and other amine salts.
  • An advandtageous salt is sodium salt.
  • Salts of the compounds of the present invention may be made by methods known to a person skilled in the art. For example, treatment of a compound of the present invention with an appropriate base or acid in an appropriate solvent can yield the corresponding salt.
  • the present invention relates to methods of treating or preventing viral infection, for example an HIV infection, in a human comprising administering to the human a therapeutically effective amount of a compound of formula (I), (II), or (III) or a pharmaceutically acceptable salt thereof in combination with one or more therapeutic agents selected from the group consisting of nucleotide reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, CCR5 antagonists, CXCR4 antagonists, fusion inhibitors, maturation inhibitors, and integrase inhibitors.
  • NRTIs nucleoside reverse transcriptase inhibitors
  • NRTIs non-nucleoside reverse transcriptase inhibitors
  • protease inhibitors CCR5 antagonists
  • CXCR4 antagonists CXCR4 antagonists
  • fusion inhibitors maturation inhibitors
  • maturation inhibitors maturation inhibitors
  • the compounds of formula (I), (II) and (III) are particularly suited to the treatment or prophylaxis of HIV infections and associated conditions.
  • Reference herein to treatment may extend to prophylaxis as well as the treatment of established infections, symptoms, and associated clinical conditions such as AIDS related complex (ARC), Kaposi's sarcoma, and AIDS dementia.
  • ARC AIDS related complex
  • Kaposi's sarcoma Kaposi's sarcoma
  • AIDS dementia dementia
  • Combination therapies comprise the administration of a compound of the present invention or a pharmaceutically acceptable salt thereof and another pharmaceutically active agent.
  • the active ingredient(s) and pharmaceutically active agents may be administered simultaneously (i.e., concurrently) in either the same or different pharmaceutical compositions or sequentially in any order.
  • the amounts of the active ingredient(s) and pharmaceutically active agent(s) and the relative timings of administration will be selected in order to achieve the desired combined therapeutic effect.
  • nucleotide reverse transcriptase inhibitors for example (S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl) cytosine (HPMPC), [[[2-(6-amino-9H-purin-9-yl)ethoxy] methyl]phosphinylidene] bis(oxymethylene)-2,2-dimethyl propanoic acid (bis-POM PMEA, adefovir dipivoxil), adefovir, [[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl] phosphonic acid (tenofovir), tenofovir disoproxil fumarate, and (R)-[[2-(6-Amino-9H-purin-9-yl)-1-methyl
  • the present invention features a combination comprising a compound of formula (I)
  • abacavir tenofovir
  • efavirenz GSK2248761
  • lersivirine lopinavir
  • fosamprenavir and atazanavir.
  • the present invention also features a combination comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents selected from abacavir, efavirenz, or lopinavir.
  • the present invention features a combination comprising of a compound of formula (I) or a pharmaceutically acceptable salt thereof, and abacavir.
  • the present invention features a method of treatment of HIV infection comprising administering to a subject, a compound of formula (I), or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents selected from the group consisting of lamivudine, abacavir, tenofovir, efavirenz, GSK2248761, lersivirine, lopinavir, fosamprenavir, and atazanavir.
  • the present invention features a method of treatment of HIV infection comprising administering to a subject, a compound of formula (I) or a pharmaceutically acceptable salt thereof, with one or more therapeutic agents selected from the group consisting of abacavir, efavirenz, and lopinavir.
  • the present invention features a method of treatment of HIV infection comprising administering to a subject a compound of formula (I) or a pharmaceutically acceptable salt thereof, and abacavir.
  • the present invention features a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents selected from the group consisting of: lamivudine, abacavir, efavirenz, tenofovir, GSK2248761, lersivirine, lopinavir, fosamprenavir, and atazanavir together with a pharmaceutically acceptable carrier therefor.
  • the present invention features a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents selected from the group consisting of: abacavir, efavirenz, and lopinavir, together with a pharmaceutically acceptable carrier therefor.
  • the present invention features a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and abacavir together with a pharmaceutically acceptable carrier therefor.
  • the present invention features a combination comprising a compound of formula (II)
  • the present invention also features a combination comprising a compound of formula (II) or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents selected from abacavir, efavirenz, and lopinavir.
  • the present invention features a combination comprising of a compound of formula (II) or a pharmaceutically acceptable salt thereof, and abacavir.
  • the present invention features a method of treatment of HIV infection comprising administering to a subject, a compound of formula (II) or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents selected from the group consisting of lamivudine, abacavir, tenofovir, efavirenz, GSK2248761, lersivirine, lopinavir, fosamprenavir, and atazanavir.
  • the present invention features a method of treatment of HIV infection comprising administering to a subject, a compound of formula (II) or a pharmaceutically acceptable salt thereof, with one or more therapeutic agents selected from the group consisting of abacavir, efavirenz, and lopinavir.
  • the present invention features a method of treatment of HIV infection comprising administering to a subject a compound of formula (II) or a pharmaceutically acceptable salt thereof, and abacavir.
  • the present invention features a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of formula (II) or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents selected from the group consisting of: lamivudine, abacavir, tenofovir, efavirenz, GSK2248761, lersivirine, lopinavir, fosamprenavir, and atazanavir together with a pharmaceutically acceptable carrier therefor.
  • the present invention features a pharmaceutical composition comprising a compound of formula (II) or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents selected from the group consisting of: abacavir, efavirenz, and lopinavir, together with a pharmaceutically acceptable carrier therefor.
  • the present invention features a pharmaceutical composition comprising a compound of formula (II) or a pharmaceutically acceptable salt thereof, and abacavir together with a pharmaceutically acceptable carrier therefor.
  • the present invention features a combination comprising a compound of formula (III)
  • the present invention also features a combination comprising a compound of formula (III) or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents selected from abacavir, efavirenz, and lopinavir.
  • the present invention also features a combination comprising a compound of formula (III) or a pharmaceutically acceptable salt thereof, and abacavir.
  • the present invention features a method of treatment of HIV infection comprising administering to a subject, a compound of formula (III) or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents selected from the group consisting of lamivudine, abacavir, tenofovir, efavirenz, GSK2248761, lersivirine, lopinavir, fosamprenavir, and atazanavir.
  • the present invention features a method of treatment of HIV infection comprising administering to a subject, a combination of a compound of formula (III) or a pharmaceutically acceptable salt thereof, with one or more therapeutic agents selected from the group consisting of abacavir, efavirenz, and lopinavir.
  • the present invention features a method of treatment of HIV infection comprising administering to a subject a compound of formula (III) or a pharmaceutically acceptable salt thereof, and abacavir.
  • the present invention features a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of formula (III) or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents selected from the group consisting of: lamivudine, abacavir, tenofovir, efavirenz, GSK2248761, lersivirine, lopinavir, fosamprenavir, and atazanavir together with a pharmaceutically acceptable carrier therefor.
  • the present invention features a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of formula (III) or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents selected from the group consisting of: abacavir, efavirenz, and lopinavir, together with a pharmaceutically acceptable carrier therefor.
  • the present invention features a pharmaceutical composition comprising a compound of formula (III) or a pharmaceutically acceptable salt thereof, and abacavir together with a pharmaceutically acceptable carrier therefor.
  • the present invention features combinations, methods of treatment, and pharmaceutical compositions as described above wherein a pharmaceutically acceptable salt of a compound of formula (I), (II) or (III) is a sodium salt.
  • the present invention features combinations, methods of treatment, and pharmaceutical compositions as described above wherein one or more therapeutic agents are a pharmaceutically acceptable salt of said therapeutic agents, for example, abacavir hemisulfate, fosamprenavir calcium, atazanavir sulfate, tenofovir disoproxil sulfate, vicriviroc maleate or bevirimat dimeglumine.
  • one or more therapeutic agents are a pharmaceutically acceptable salt of said therapeutic agents, for example, abacavir hemisulfate, fosamprenavir calcium, atazanavir sulfate, tenofovir disoproxil sulfate, vicriviroc maleate or bevirimat dimeglumine.
  • the present invention features methods of treatment as described above wherein the subject is a human.
  • the present invention features combinations, methods of treatment and pharmaceutical compositions as described above wherein the combination is administered sequentially.
  • the present invention features combinations, methods of treatment and pharmaceutical compositions as described above wherein the combination is administered simultaneously or concurrently.
  • Abacavir may be made by methods disclosed in U.S. Pat. Nos. 5,034,394; 5,089,500; 6,294,540; 5,641,889; 5,840,990; 5,919,941; 5,808,147; 6,392,085; 6,448,403; 5,917,041; 6,087,501; 5,917,042; 6,555,687; 6,552,193; 6,870,053; 6,294,540; 6,340,587; or 6,646,125.
  • Lamivudine may be made by methods disclosed in U.S. Pat. Nos. 5,047,407; 7,119,202; 5,905,082; 5,696,254; 5,663,320; 5,693,787; 6,051,709; or 6,329,522.
  • Tenofovir may be made by U.S. Pat. Nos. 5,922,695; 5,935,946; 5,977,089; 6,043,230, 6,069,249.
  • Efavirenz may be made by may be made by methods disclosed in U.S. Pat. Nos. 5,519.021; 5,663,169; 5,811,423; 6,555,133; 6,639,071; or 6,939,964.
  • GSK2248761 may be made by methods disclosed in U.S. Pat. No. 7,534,809.
  • Lersivirine may be made by methods disclosed in U.S. Pat. No. 7,109,228.
  • Lopinavir may be made by methods disclosed in U.S. Pat. No. 5,914,332.
  • Fosamprenavir may be made by methods disclosed in U.S. Pat. Nos. 6,436,989; 6,514,953; or 6,281,367.
  • Atazanavir may be made by methods disclosed in U.S. Pat. Nos. 5,849,911 or 6,087,383.
  • the therapeutic agents of the combinations may be made according to published methods or by any method known to those skilled in the art.
  • a compound of formula (I), (II) or (III) or a pharmaceutically acceptable salt thereof may be formulated into compositions together with one or more therapeutic agents.
  • the composition may be pharmaceutical composition, which comprises a compound of formula (I), (II), or (III), one or more therapeutic agents, and a pharmaceutically acceptable carrier, adjuvant or vehicle.
  • the composition comprises an amount of a combination of the present invention effective to treat or prevent viral infection, for example an HIV infection, in a biological sample or in a patient.
  • combinations of the invention and pharmaceutical compositions thereof comprising an amount of a combination of the present invention effective to inhibit viral replication or to treat or prevent a viral infection or disease or disorder, for example an HIV infection, and a pharmaceutically acceptable carrier, adjuvant or vehicle, may be formulated for administration to a patient, for example, for oral administration.
  • the present invention features combinations according to the invention for use in medical therapy, for example for the treatment or prophylaxis of a viral infection, for example an HIV infection and associated conditions.
  • the compounds according to the invention are especially useful for the treatment of AIDS and related clinical conditions such as AIDS related complex (ARC), progressive generalized lymphadenopathy (PGL), Kaposi's sarcoma, thromobocytopenic purpura, AIDS-related neurological conditions such as AIDS dementia complex, multiple sclerosis or tropical paraperesis, anti-HIV antibody-positive and HIV-positive conditions, including such conditions in asymptomatic patients.
  • the present invention provides a method for the treatment or prevention of the symptoms or effects of a viral infection in an infected patient, for example, a mammal including a human, which comprises administering to said patient a pharmaceutically effective amount of a combination according to the invention.
  • the viral infection is a retroviral infection, in particular an HIV infection.
  • the present invention further includes the use of a combination according to the invention in the manufacture of a medicament for simultaneous (concurrent) or sequential administration to a subject for the treatment of a viral infection, in particular and HIV infection.
  • the present invention further provides a method for the treatment of a clinical condition in a patient, for example, a mammal including a human which clinical condition includes those which have been discussed hereinbefore, which comprises treating said patient with a pharmaceutically effective amount of a compound according to the invention.
  • the present invention also includes a method for the treatment or prophylaxis of any of the aforementioned diseases or conditions.
  • Compounds of the present invention may be administered with an agent known to inhibit or reduce the metabolism of compounds, for example ritonavir. Accordingly, the present invention features a method for the treatment or prophylaxis of a disease as hereinbefore described by administration of a compound of the present invention in combination with a metabolic inhibitor. Such combination may be administered simultaneously or sequentially.
  • a suitable dose for each of the above-mentioned conditions will be in the range of 0.01 to 250 mg per kilogram body weight of the recipient (e.g. a human) per day, in the range of 0.1 to 100 mg per kilogram body weight per day; in the range 1 to 30 mg per kilogram body weight per day; in the range 0.5 to 20 mg per kilogram body weight per day.
  • all weights of active ingredients are calculated as the parent compound of formula (I), (II), or (III) and other therapeutic agents. For salts thereof, the weights would be increased proportionally.
  • the desired dose may be presented as one, two, three, four, five, six or more sub-doses administered at appropriate intervals throughout the day. In some cases the desired dose may be given on alternative days. These sub-doses may be administered in unit dosage forms, for example, containing 1 to 2000 mg; 5 to 500 mg; 10 to 400 mg, 20 to 300 mg of each active ingredient per unit dosage form.
  • the combinations may be administered to achieve peak plasma concentrations of each active ingredient.
  • compositions of the present invention comprise an active ingredient, as defined above, together with one or more acceptable carriers thereof and one or more additional therapeutic agents.
  • Each carrier must be acceptable in the sense of being compatible with the other ingredients of the composition and not injurious to the patient.
  • compositions include those suitable for oral, rectal, nasal, topical (including transdermal, buccal and sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous, intradermal, and intravitreal) administration.
  • the compositions may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy. Such methods represent a further feature of the present invention and include the step of bringing into association the active ingredients with the carrier, which constitutes one or more accessory ingredients.
  • the compositions are prepared by uniformly and intimately bringing into association the active ingredients with liquid carriers or finely divided solid carriers or both, and then if necessary shaping the product.
  • the present invention further includes a pharmaceutical composition as hereinbefore defined wherein a compound of the present invention or a pharmaceutically acceptable derivative thereof and another therapeutic agent are presented separately from one another as a kit of parts.
  • compositions suitable for transdermal administration may be presented as discrete patches adapted to remain in intimate contact with the epidermis of the recipient for a prolonged period of time.
  • patches suitably contain the active compound 1) in an optionally buffered, aqueous solution or 2) dissolved and/or dispersed in an adhesive or 3) dispersed in a polymer.
  • a suitable concentration of the active compound is about 1% to 25%, preferably about 3% to 15%.
  • the active compound may be delivered from the patch by electrotransport or iontophoresis as generally described in Pharmaceutical Research 3(6), 318 (1986).
  • compositions of the present invention suitable for oral administration may be presented as discrete units such as capsules, caplets, cachets or tablets each containing a predetermined amount of the active ingredients; as a powder or granules; as a solution or a suspension in an aqueous or non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion.
  • the active ingredient may also be presented as a bolus, electuary or paste.
  • a tablet may be made by compression or molding, optionally with one or more accessory ingredients.
  • Compressed tablets may be prepared by compressing in a suitable machine the active ingredients in a free-flowing form such as a powder or granules, optionally mixed with a binder (e.g. povidone, gelatin, hydroxypropylmethyl cellulose), lubricant, inert diluent, preservative, disintegrant (e.g. sodium starch glycollate, cross-linked povidone, cross-linked sodium carboxymethyl cellulose) surface-active or dispersing agent.
  • Molded tablets may be made by molding a mixture of the powdered compound moistened with an inert liquid diluent in a suitable machine.
  • the tablets may optionally be coated or scored and may be formulated so as to provide slow or controlled release of the active ingredients therein using, for example, hydroxypropylmethyl cellulose in varying proportions to provide the desired release profile. Tablets may optionally be provided with an enteric coating, to provide release in parts of the gut other than the stomach.
  • compositions suitable for topical administration in the mouth include lozenges comprising the active ingredients in a flavored base, usually sucrose and acacia or tragacanth; pastilles comprising the active ingredient in an inert basis such as gelatin and glycerin, or sucrose and acacia; and mouthwashes comprising the active ingredient in a suitable liquid carrier.
  • compositions suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or spray.
  • Pharmaceutical compositions may contain in addition to the active ingredient such carriers as are known in the art to be appropriate.
  • compositions for rectal administration may be presented as a suppository with a suitable carrier comprising, for example, cocoa butter or a salicylate or other materials commonly used in the art.
  • a suitable carrier comprising, for example, cocoa butter or a salicylate or other materials commonly used in the art.
  • the suppositories may be conveniently formed by admixture of the active combination with the softened or melted carrier(s) followed by chilling and shaping in molds.
  • compositions suitable for parenteral administration include aqueous and nonaqueous isotonic sterile injection solutions which may contain anti-oxidants, buffers, bacteriostats and solutes which render the pharmaceutical composition isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents; and liposomes or other microparticulate systems which are designed to target the compound to blood components or one or more organs.
  • the pharmaceutical compositions may be presented in unit-dose or multi-dose sealed containers, for example, ampoules and vials, and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example water for injection, immediately prior to use.
  • Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described.
  • Unit dosage pharmaceutical compositions include those containing a daily dose or daily subdose of the active ingredients, as hereinbefore recited, or an appropriate fraction thereof.
  • compositions of the present invention may be presented as patient packs containing one or more courses of treatment in a single package, for example, a blister pack. It will be understood that the administration of the combination of the invention by means of a single patient pack, or patient packs of each composition, is an additional feature of the invention.
  • compositions of this invention may include other agents conventional in the art having regard to the type of pharmaceutical composition in question, for example, those suitable for oral administration may include such further agents as sweeteners, thickeners and flavoring agents.
  • Antiviral HIV activity was measured by means of a tetrazolium-based colorimetric procedure in the human T-cell leukemia virus (HTLV-1) transformed cell line MT-4. Aliquots of test compound were diluted vertically across a deep-well master assay plate, in medium (RPMI 1640, 10% vol./vol. fetal bovine serum (FBS), and 10 ⁇ g/mL gentamicin), at concentrations that were approximately 40-fold higher than the final assay concentration. Serial dilutions were made at either 1:2 or 1:3.16 ratios. HIV inhibitors were diluted horizontally across master assay plates, also in concentrations that were approximately 40-fold higher than the final assay concentration.
  • medium RPMI 1640, 10% vol./vol. fetal bovine serum (FBS), and 10 ⁇ g/mL gentamicin
  • IL-2 10 ⁇ g/mL gentamicin
  • IL-2 10 ⁇ g/mL gentamicin
  • Cell aliquots were infected by the addition of HIV-1 (strain IIIB) diluted to give a viral multiplicity of infection (MOI) of 73 pfU per 1 ⁇ 10 4 cells.
  • MOI viral multiplicity of infection
  • a similar cell aliquot was diluted with medium to provide a mock-infected control.
  • Cell infection was allowed to proceed for 1 hour at 37° C. in a tissue culture incubator with humidified 5% CO 2 atmosphere. After the 1 hour incubation the virus/cell suspension was added to each well of the plates containing pre-diluted compounds. Plates were then placed in a tissue culture incubator with humidified 5% CO 2 for 5 days.
  • HIV-1 Strain IIIB Wild-type Laboratory Strain
  • Virus Titer 6.896 E4 TCID 50 /mL.
  • the readout in the MT-4 cell assay utilizes MTS, a tetrazolium-based staining reagent where changes in optical density (O.D.) of the reagent are used to estimate the total cell number remaining after treatment.
  • Final MT-4 cell numbers may decrease due to two effects.
  • an HIV-induced cytotoxicity may occur when HIV kills greater than 75% of the MT-4 cells during the 5 days following infection.
  • a compound-induced cytotoxicity may occur, where the compound either directly kills the MT-4 cells or prevents cell growth (stasis) over the 5 days in either infected or uninfected cells.
  • a compound of formula (I) was found to be additive with raltegravir, adefovir, and maraviroc and was not affected by the presence of ribavirin.
  • a compound of formula (I) was found to be synergistic with stavudine, abacavir, efavirenz, nevirapine, lopinavir, amprenavir, enfuvirtide.

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Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SMT201800290T1 (it) 2010-01-27 2018-07-17 Viiv Healthcare Co Terapia antivirale
NZ706223A (en) 2012-10-23 2018-11-30 Cipla Ltd Pharmaceutical antiretroviral composition
PE20151499A1 (es) 2012-12-21 2015-10-29 Gilead Sciences Inc Compuestos de carbamoilpiridona policiclicos y su uso farmaceutico
EP2767272A1 (fr) * 2013-02-18 2014-08-20 Ratiopharm GmbH Forme posologique pharmaceutique solide de dolutegravir
CA2897137A1 (fr) * 2013-02-18 2014-08-21 Ratiopharm Gmbh Forme galenique pharmaceutique solide de dolutegravir
EP3252058B1 (fr) 2013-07-12 2021-01-20 Gilead Sciences, Inc. Composés polycycliques-carbamoylpyridone et leur utilisation pour le traitement des infections par vih
NO2865735T3 (fr) 2013-07-12 2018-07-21
AU2014324829B2 (en) 2013-09-27 2017-09-07 Merck Sharp & Dohme Corp. Substituted Quinolizine Derivatives useful as HIV integrase inhibitors
IN2014MU00916A (fr) 2014-03-20 2015-09-25 Cipla Ltd
EP3151920B1 (fr) 2014-06-04 2025-08-06 Sanford-Burnham Medical Research Institute Utilisation d'un inhibiteur des antagonistes de la protéine d'apoptose (iap) dans une thérapie contre le vih
TWI744723B (zh) 2014-06-20 2021-11-01 美商基利科學股份有限公司 多環型胺甲醯基吡啶酮化合物之合成
NO2717902T3 (fr) 2014-06-20 2018-06-23
TW201613936A (en) 2014-06-20 2016-04-16 Gilead Sciences Inc Crystalline forms of(2R,5S,13aR)-8-hydroxy-7,9-dioxo-n-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide
JP6603306B2 (ja) 2014-07-29 2019-11-06 レツク・フアーマシユーテイカルズ・デー・デー ドルテグラビルナトリウムの新規な水和物
TWI695003B (zh) 2014-12-23 2020-06-01 美商基利科學股份有限公司 多環胺甲醯基吡啶酮化合物及其醫藥用途
KR20190057158A (ko) 2015-04-02 2019-05-27 길리애드 사이언시즈, 인코포레이티드 폴리시클릭-카르바모일피리돈 화합물 및 그의 제약 용도
EP3334419A1 (fr) * 2015-08-14 2018-06-20 Sandoz AG Composition pharmaceutique solide d'abacavir, de lamivudine et d'éfavirenz
WO2017205585A1 (fr) * 2016-05-27 2017-11-30 Viiv Healthcare Company Combinaisons, utilisations et traitements correspondants
WO2018028841A1 (fr) * 2016-08-12 2018-02-15 Sandoz Ag Composé pharmaceutique solide d'abacavir, de lamivudine et d'éfavirenz.
WO2018042332A1 (fr) * 2016-08-31 2018-03-08 Glaxosmithkline Intellectual Property (No.2) Limited Combinaisons, utilisations et traitements correspondants
US20200138845A1 (en) * 2017-07-18 2020-05-07 Viiv Healthcare Company Combination Drug Therapy
JP7384783B2 (ja) 2017-07-21 2023-11-21 ヴィーブ ヘルスケア カンパニー Ｈｉｖ感染症及びａｉｄｓを治療するためのレジメン
US20200147092A1 (en) * 2017-07-21 2020-05-14 Viiv Healthcare Company Regimens for treating hiv infections and aids
MX2020003377A (es) * 2017-10-13 2020-09-28 Viiv Healthcare Co Formulacion de tableta farmaceutica de dos capas.
TW202544011A (zh) 2019-03-22 2025-11-16 美商基利科學股份有限公司 橋鍵聯三環胺甲醯吡啶酮化合物及其醫藥用途
CN114901363A (zh) * 2020-01-09 2022-08-12 华盛顿大学 长效治疗剂组合物及其方法
JP7453399B2 (ja) 2020-02-24 2024-03-19 ギリアード サイエンシーズ， インコーポレイテッド Ｈｉｖ感染症を治療するための四環式化合物及びその使用
KR20230079137A (ko) 2020-09-30 2023-06-05 길리애드 사이언시즈, 인코포레이티드 가교된 트리사이클릭 카르바모일피리돈 화합물 및 이의 용도
PL4196479T3 (pl) 2021-01-19 2024-03-18 Gilead Sciences, Inc. Podstawione związki pirydotriazynowe i ich zastosowania
CN114230579A (zh) * 2021-11-12 2022-03-25 南京艾迪医药科技有限公司 多环氨基甲酰基吡啶酮衍生物及其制备方法和药物组合物
AU2023225805A1 (en) * 2022-02-28 2024-10-17 Jericho Sciences, Llc Methods for viral infections
TWI856796B (zh) 2022-04-06 2024-09-21 美商基利科學股份有限公司 橋聯三環胺甲醯基吡啶酮化合物及其用途

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006116764A1 (fr) * 2005-04-28 2006-11-02 Smithkline Beecham Corporation Derive polycyclique de la carbamoylpyridone a activite inhibitrice sur l'integrase du vih
US20070124152A1 (en) * 2004-02-11 2007-05-31 Johns Brian A Hiv Integrase Inhibitors
WO2009082819A1 (fr) * 2008-01-03 2009-07-09 Virochem Pharma Inc. Nouveaux dérivés de lupane

Family Cites Families (75)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5047407A (en) 1989-02-08 1991-09-10 Iaf Biochem International, Inc. 2-substituted-5-substituted-1,3-oxathiolanes with antiviral properties
US7119202B1 (en) 1989-02-08 2006-10-10 Glaxo Wellcome Inc. Substituted-1,3-oxathiolanes and substituted-1,3-dioxolanes with antiviral properties
GB8815265D0 (en) 1988-06-27 1988-08-03 Wellcome Found Therapeutic nucleosides
GB9009861D0 (en) 1990-05-02 1990-06-27 Glaxo Group Ltd Chemical compounds
ZA923641B (en) 1991-05-21 1993-02-24 Iaf Biochem Int Processes for the diastereoselective synthesis of nucleosides
GB9111902D0 (en) 1991-06-03 1991-07-24 Glaxo Group Ltd Chemical compounds
GB9204015D0 (en) 1992-02-25 1992-04-08 Wellcome Found Therapeutic nucleosides
US5663169A (en) 1992-08-07 1997-09-02 Merck & Co., Inc. Benzoxazinones as inhibitors of HIV reverse transcriptase
IL106507A (en) 1992-08-07 1997-11-20 Merck & Co Inc Pharmaceutical compositions containing benzoxazinones and some novel compounds of this type
GB9402161D0 (en) 1994-02-04 1994-03-30 Wellcome Found Chloropyrimidine intermediates
IL113432A (en) 1994-04-23 2000-11-21 Glaxo Group Ltd Process for the diastereoselective synthesis of nucleoside analogues
UA49803C2 (uk) 1994-06-03 2002-10-15 Дж.Д. Сьорль Енд Ко Спосіб лікування ретровірусних інфекцій
MY115461A (en) 1995-03-30 2003-06-30 Wellcome Found Synergistic combinations of zidovudine, 1592u89 and 3tc
US5914332A (en) 1995-12-13 1999-06-22 Abbott Laboratories Retroviral protease inhibiting compounds
US5849911A (en) 1996-04-22 1998-12-15 Novartis Finance Corporation Antivirally active heterocyclic azahexane derivatives
AU727983B2 (en) * 1996-06-25 2001-01-04 Glaxo Group Limited Combinations comprising VX478, zidovudine, FTC and/or 3TC for use in the treatment of HIV
US5922695A (en) 1996-07-26 1999-07-13 Gilead Sciences, Inc. Antiviral phosphonomethyoxy nucleotide analogs having increased oral bioavarilability
US5965729A (en) 1997-02-05 1999-10-12 Merck & Co., Inc. Process for the crystallization of a reverse transcriptase inhibitor using an anti-solvent
GB9709945D0 (en) 1997-05-17 1997-07-09 Glaxo Group Ltd A novel salt
US5935946A (en) 1997-07-25 1999-08-10 Gilead Sciences, Inc. Nucleotide analog composition and synthesis method
GB9717928D0 (en) 1997-08-22 1997-10-29 Glaxo Group Ltd Process for the enatioselective hydrolysis of n-derivatised lactams
GB9721780D0 (en) 1997-10-14 1997-12-10 Glaxo Group Ltd Process for the synthesis of chloropurine intermediates
US6436989B1 (en) 1997-12-24 2002-08-20 Vertex Pharmaceuticals, Incorporated Prodrugs of aspartyl protease inhibitors
US6087383A (en) 1998-01-20 2000-07-11 Bristol-Myers Squibb Company Bisulfate salt of HIV protease inhibitor
GB9805898D0 (en) 1998-03-20 1998-05-13 Glaxo Group Ltd Process for the sythesis of hiv protease inhibitors
AU3366899A (en) 1998-03-27 1999-10-18 Regents Of The University Of California, The Novel hiv integrase inhibitors and hiv therapy based on drug combinations including integrase inhibitors
UA72207C2 (uk) 1998-04-07 2005-02-15 Брістол- Майєрс Сквібб Фарма Компані Фармацевтична композиція ефавіренцу з добавкою дезінтегруючих агентів у вигляді швидкорозчинних капсул або таблеток та спосіб її виготовлення
GB9809213D0 (en) * 1998-04-29 1998-07-01 Glaxo Group Ltd Pharmaceutical compositions
GB9815567D0 (en) 1998-07-18 1998-09-16 Glaxo Group Ltd Antiviral compound
AU784782B2 (en) 2000-01-31 2006-06-15 Cook Biotech, Incorporated Stent valves and uses of same
BRPI0208811B8 (pt) 2001-04-10 2021-05-25 Pfizer derivados de pirazol, seu uso e processo de preparação, bem como composição farmacêutica compreendendo os mesmos
MY169670A (en) 2003-09-03 2019-05-08 Tibotec Pharm Ltd Combinations of a pyrimidine containing nnrti with rt inhibitors
US7638522B2 (en) * 2001-08-13 2009-12-29 Janssen Pharmaceutica N.V. Salt of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino] benzonitrile
JO3429B1 (ar) 2001-08-13 2019-10-20 Janssen Pharmaceutica Nv مشتقات برميدينات مثبطة فيروس الايدز
TW200403061A (en) 2002-06-04 2004-03-01 Glaxo Group Ltd Pharmaceutical compositions
CN1302779C (zh) * 2002-06-27 2007-03-07 美迪维尔公司 含有阿巴卡韦和阿洛夫定的药物制剂及其用途
EA201100293A1 (ru) * 2003-01-14 2011-08-30 Джилид Сайэнс, Инк. Способ (варианты) и фармацевтическая композиция (варианты) для лечения или профилактики симптомов вич-инфекции
TW200510425A (en) 2003-08-13 2005-03-16 Japan Tobacco Inc Nitrogen-containing fused ring compound and use thereof as HIV integrase inhibitor
JP4285353B2 (ja) 2004-03-05 2009-06-24 清水建設株式会社 化学物質放散度評価方法
EP1742642B1 (fr) * 2004-04-14 2008-10-15 Gilead Sciences, Inc. Analogues de phosphonate de composes inhibiteurs de l'integrase du vih
EP3287130A1 (fr) 2004-05-21 2018-02-28 Japan Tobacco Inc. Combinaisons comportant un dérivé d'isoquinolone 4 et inhibiteurs de la protease
US7176196B2 (en) 2004-05-28 2007-02-13 Bristol-Myers Squibb Company Bicyclic heterocycles as HIV integrase inhibitors
EP1930011B1 (fr) 2004-08-23 2011-08-17 Teva Pharmaceutical Industries Ltd Forme cristalline de ibandronate de sodium
WO2006024668A1 (fr) 2004-09-02 2006-03-09 Janssen Pharmaceutica N.V. Chlorhydrate de 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethyl-phenyl]amino]-2-pyrimidinyl]amino]benzonitrile
ATE479693T1 (de) 2004-09-17 2010-09-15 Idenix Pharmaceuticals Inc Phosphoindole als hiv-inhibitoren
US7250421B2 (en) 2005-01-31 2007-07-31 University Of Georgia Research Foundation, Inc. Diketo acids with nucleobase scaffolds: anti-HIV replication inhibitors targeted at HIV integrase
US20090093454A1 (en) 2005-03-04 2009-04-09 Kristjan Gudmundsson Chemical Compounds
UA96568C2 (en) * 2005-04-28 2011-11-25 Глаксосмиткляйн Ллк Polycyclic carbamoyl pyridone derivative as hiv-integrase inhibitor
CA2610029A1 (fr) 2005-06-01 2006-12-07 Bioalliance Pharma Combinaisons synergiques comprenant un compose de styrylquinoleine et d'autres agents therapeutiques contre une infection au vih
UA108605C2 (uk) * 2005-12-30 2015-05-25 Спосіб покращення фармакокінетики інгібіторів інтегрази віл
SG170795A1 (en) 2005-12-30 2011-05-30 Gilead Sciences Inc Methods for improving the pharmacokinetics of hiv integrase inhibitors
JP5754005B2 (ja) * 2006-01-20 2015-07-22 ヤンセン・アールアンドデイ・アイルランド Ｔｃｍ２７８を用いるｈｉｖ−感染症の長期間処置
US20080039428A1 (en) 2006-06-29 2008-02-14 Panacos Pharmaceuticals, Inc. Antiretroviral combination therapy
PT2069303E (pt) 2006-07-21 2016-06-08 Gilead Sciences Inc Inibidores de protease antiviral
NZ575831A (en) 2006-09-29 2011-12-22 Idenix Pharmaceuticals Inc Enantiomerically pure phosphoindoles as hiv inhibitors
PL2487161T5 (pl) 2007-02-23 2024-09-09 Gilead Sciences, Inc. <div>Modulatory właściwości farmakokinetycznych środków terapeutycznych</div><div> </div>
TW200835693A (en) 2007-02-23 2008-09-01 Auspex Pharmaceuticals Inc Preparation and utility of non-nucleoside reverse transcriptase inhibitors
US8354421B2 (en) 2007-06-29 2013-01-15 Korea Research Insitute Of Chemical Technology HIV reverse transcriptase inhibitors
EA200971115A1 (ru) 2007-06-29 2010-04-30 Корея Рисерч Инститьют Оф Кемикал Текнолоджи Новые ингибиторы обратной транскриптазы вич
CA2692331A1 (fr) 2007-07-06 2009-01-15 Gilead Sciences, Inc. Modulateurs des proprietes pharmacocinetiques de substances therapeutiques
HRP20131128T1 (hr) * 2007-07-12 2013-12-20 Janssen R&D Ireland Kristalni oblik (e) 4-[[4-[[4-(2-cijanoetenil)-2,6-dimetilfenil]amino]-2-pirimidinil]amino]benzonitrila
WO2009058923A1 (fr) 2007-10-31 2009-05-07 Smithkline Beecham Corporation Antagonistes de ccr5 en tant qu'agents thérapeutiques
EP2217573A4 (fr) 2007-11-01 2011-08-31 Uab Research Foundation Traitement et prévention d'infections virales
US8108055B2 (en) 2007-12-28 2012-01-31 Larry Wong Method, system and apparatus for controlling an electrical device
MX2010007374A (es) 2008-01-03 2010-10-05 Virochem Pharma Inc Nuevos derivados de c-21-ceto lupano, preparacion y uso de los mismos.
AU2008346823B2 (en) 2008-01-04 2015-03-12 Gilead Sciences, Inc. Inhibitors of cytochrome P450
JP2011511812A (ja) 2008-02-14 2011-04-14 バイロケム ファーマ インコーポレイテッド 新規１７βルパン誘導体
WO2009148600A2 (fr) * 2008-06-06 2009-12-10 Concert Pharmaceuticals, Inc. Composés à base de lysine deutérée
DK2320908T3 (en) * 2008-07-25 2014-03-10 Viiv Healthcare Co DOLUTEGRAVIR prodrugs
JP5572168B2 (ja) 2008-12-11 2014-08-13 ビーブ・ヘルスケア・カンパニー カルバモイルピリドンｈｉｖインテグラーゼ阻害剤の製造方法および中間体
JP5086478B2 (ja) 2008-12-11 2012-11-28 塩野義製薬株式会社 カルバモイルピリドンｈｉｖインテグラーゼ阻害剤及びそれらの中間体の合成
SMT201800290T1 (it) 2010-01-27 2018-07-17 Viiv Healthcare Co Terapia antivirale
GB201006038D0 (en) 2010-04-12 2010-05-26 Unilever Plc Improvements relating to antiviral compositions
CN103402516B (zh) 2010-06-17 2018-01-30 富津世生物技术有限公司 用作抗病毒药物的化合物、组合物及使用方法
AU2012236332A1 (en) 2011-04-01 2013-10-31 Chiesi Farmaceutici S.P.A. Short -acting dihydropyridines (clevidipine) for use in reducing stroke damage

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070124152A1 (en) * 2004-02-11 2007-05-31 Johns Brian A Hiv Integrase Inhibitors
WO2006116764A1 (fr) * 2005-04-28 2006-11-02 Smithkline Beecham Corporation Derive polycyclique de la carbamoylpyridone a activite inhibitrice sur l'integrase du vih
WO2009082819A1 (fr) * 2008-01-03 2009-07-09 Virochem Pharma Inc. Nouveaux dérivés de lupane

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Clercq "Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV," International Journal of Antimicrobial Agents," 2009, Vol. 33, pp 307-320 *
Damond et al. "Virological and immunological response to HAART regimen containing integrase inhibitor in HIV-2-infdected patients," AIDS, 2008, Vol. 22, No. 5, pp 663-668 *

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