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WO2000029414A1 - Dialkyl-1-aryl-1-(2,4-dioxo-5-amino-1,3-pyrimidin-5-yl)methylphosphonates - Google Patents

Dialkyl-1-aryl-1-(2,4-dioxo-5-amino-1,3-pyrimidin-5-yl)methylphosphonates Download PDF

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Publication number
WO2000029414A1
WO2000029414A1 PCT/RU1998/000386 RU9800386W WO0029414A1 WO 2000029414 A1 WO2000029414 A1 WO 2000029414A1 RU 9800386 W RU9800386 W RU 9800386W WO 0029414 A1 WO0029414 A1 WO 0029414A1
Authority
WO
WIPO (PCT)
Prior art keywords
compounds
different
dioxo
amino
dialkyl
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.)
Ceased
Application number
PCT/RU1998/000386
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English (en)
Russian (ru)
Inventor
Viktor Iosifovich Krutikov
Viktor Veniaminovich Tets
Rimma Iliinichna Ashkinazi
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.)
Individual
Original Assignee
Individual
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
Application filed by Individual filed Critical Individual
Priority to PCT/RU1998/000386 priority Critical patent/WO2000029414A1/fr
Priority to AU26451/99A priority patent/AU2645199A/en
Publication of WO2000029414A1 publication Critical patent/WO2000029414A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6509—Six-membered rings
    • C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3

Definitions

  • the invention is related to medicine, more specifically, to pharmaceuticals, and to selective biological compounds, which are substituted by aminomethylphosphates.
  • Declared compounds have a high potency in the case of viruses and simple antibiotic activity in the presence of a medicine.
  • Compounds are intended, mainly, for use in medical practice for the treatment of viral infections, diseases, and related immunodeficiencies, as well as tuberculosis.
  • ⁇ cyclopentyl. cyclohexyl, alkyl, aryl, tolyl, imidazole.
  • ⁇ -, ⁇ , amino acid residue
  • ⁇ ⁇ , alkyl, alkenyl, cycloalkyl, alkoxyalkyl.
  • ⁇ ⁇ or ⁇ .
  • V is selected from the group
  • the task of the invention is reduced to the chemical synthesis of new biologically active substances, which are not reflected in the above-mentioned analogs.
  • ⁇ is selected from the group: alkyl, galogen, hydrothermal. not ⁇ ; ⁇ 2 is selected from the group: alkyl, ⁇ 2 ⁇ 2 ⁇ 2.
  • dialkyl-1-aryl-1- (2,4-dioxo-5-amino-1,3-pyrimidin-5-yl) methyls is found in the assay. 1
  • 2,4-dioxo-5-arylidenimine-1,3-pyrimidines which are intermediate compounds for the synthesis of the targeting compounds, receive the interaction of 5-aminourazyl with the corresponding compounds.
  • a mixture of ethanol-water is used 1: 1. When the mixture of aldehyde with aminouracil is boiled, a colorless crystalline precipitate is precipitated.
  • PRODUCTS ARE RECEIVED WITH YEARS OF 45-95% FROM THEORETICAL.
  • the flask contains 1 g of 2,4-dioxo-5-arylidenimino-1,3-pyrimidine and 7 ml of dibutyl phosphate.
  • the mixture is heated at a temperature of 80-90 ° C and stirred, at the same time a colorless plant is formed.
  • the reactive mass is added to it with 50 ml of sulfur.
  • the plant is filtered, washed, dried.
  • the yield of the product is 83%. ⁇ . ⁇ lav. 203 ° C.
  • the other declared compounds synthesize similarly.
  • the compounds of the general formula provide non-color crystalline substances, which are dissolved in dimethyl sulfide, pyridine.
  • Individualn ⁇ s ⁇ vesches ⁇ v d ⁇ azana me ⁇ d ⁇ m ⁇ n ⁇ sl ⁇ yn ⁇ y ⁇ ma ⁇ g ⁇ a ⁇ ii on ⁇ las ⁇ in ⁇ a ⁇ ⁇ i ⁇ ⁇ -254 elyuen ⁇ che ⁇ y ⁇ e ⁇ l ⁇ is ⁇ y ugle ⁇ d - iz ⁇ an ⁇ l 9: 1.
  • the manufacturer’s interface (DSS) is toxic. * - ⁇ ID - tkanevy infectious dose.
  • EXPERIMENT Z The division of the maximum transferable dose.
  • the test compound was administered with an external stomach tube (300 mg / kg) or an internal (100 mg / kg) white non-linear 10
  • mice weighing 18-20 g at most 3 males and 3 females in each of the test groups), after which we observed their state for 72 hours.
  • the absence of symptoms, property-related toxic effects, and the absence of death of animals during the course of the indicated period results in a decrease in the rate of inconvenience.
  • With the presence of acute toxic effects of the dose decreases to detect the maximum transmissible dose [7].
  • mice The results obtained testify that, in addition to the claimed compounds at a concentration of 300 mg / kg, they do not have a toxicity rate for mice.
  • V-containing viruses vesicular vesicles and myriasis viri

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention se rapporte au domaine de la médecine, plus précisément à celui de la pharmacologie, et concerne des composés synthétiques bioactifs qui consistent en des aminométhylphosphonates substitués. Cette invention a pour but de produire de nouveaux composés chimiques qui possèdent une activité biologique étendue, notamment une activité antivirale (contre les virus de l'herpès simplex) et une activité antimicrobienne. En d'autres termes, cette invention a pour but d'effectuer la synthèse chimique de nouvelles substances bioactives qui s'avèrent meilleures que les analogues existants sur plusieurs points, notamment en ce qui concerne l'étendue de leur action. A cette fin, on procède à la synthèse de dialkyl-1-aryl-1-(2,4-dioxo-5-amino-1,3-pyrimidin-5-yl)méthylphosphonates qui correspondent à la formule générale (I) où R1 représente alkyle, halogène, hydroxyle ou nitro, tandis que R2 représente alkyle ou HCF2CF2CH2. Cette invention concerne également une méthodologie générale de production de ces composés, un exemple de synthèse, une liste de 13 substances synthétisées et testées, les résultats de leur identification, ainsi que des données expérimentales portant sur 3 séries de vérification comparative de leurs propriétés biologiques et de leur toxicité.
PCT/RU1998/000386 1998-11-18 1998-11-18 Dialkyl-1-aryl-1-(2,4-dioxo-5-amino-1,3-pyrimidin-5-yl)methylphosphonates Ceased WO2000029414A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/RU1998/000386 WO2000029414A1 (fr) 1998-11-18 1998-11-18 Dialkyl-1-aryl-1-(2,4-dioxo-5-amino-1,3-pyrimidin-5-yl)methylphosphonates
AU26451/99A AU2645199A (en) 1998-11-18 1998-11-18 Dialkyl-1-aryl-1-(2,4-dioxo-5-amino-1,3-pyrimidin-5-yl)methy lphosphonates

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/RU1998/000386 WO2000029414A1 (fr) 1998-11-18 1998-11-18 Dialkyl-1-aryl-1-(2,4-dioxo-5-amino-1,3-pyrimidin-5-yl)methylphosphonates

Publications (1)

Publication Number Publication Date
WO2000029414A1 true WO2000029414A1 (fr) 2000-05-25

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PCT/RU1998/000386 Ceased WO2000029414A1 (fr) 1998-11-18 1998-11-18 Dialkyl-1-aryl-1-(2,4-dioxo-5-amino-1,3-pyrimidin-5-yl)methylphosphonates

Country Status (2)

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AU (1) AU2645199A (fr)
WO (1) WO2000029414A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8101745B2 (en) 2004-12-16 2012-01-24 The Regents Of The University Of California Lung-targeted drugs
US9775852B2 (en) 2013-03-15 2017-10-03 The Regents Of The University Of California Acyclic nucleoside phosphonate diesters
US9801884B2 (en) 2014-09-15 2017-10-31 The Regents Of The University Of California Nucleotide analogs
US10377782B2 (en) 2015-09-15 2019-08-13 The Regents Of The University Of California Nucleotide analogs
US12329768B2 (en) 2022-07-21 2025-06-17 Antiva Biosciences, Inc. Compositions and dosage forms for treatment of HPV infection and HPV-induced neoplasia

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0206459A2 (fr) * 1985-04-25 1986-12-30 Ceskoslovenska akademie ved (Phosphonylméthoxyalkyl)-9-adénines, leur méthode de préparation et leur utilisation
US5247085A (en) * 1987-11-30 1993-09-21 Beecham Group P.L.C. Antiviral purine compounds
WO1995024410A1 (fr) * 1994-03-08 1995-09-14 Otsuka Pharmaceutical Factory, Inc. Derive de diester phosphonique
WO1998017672A1 (fr) * 1996-10-24 1998-04-30 Novartis Ag Acides aminoalcanophosphoniques substitues

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0206459A2 (fr) * 1985-04-25 1986-12-30 Ceskoslovenska akademie ved (Phosphonylméthoxyalkyl)-9-adénines, leur méthode de préparation et leur utilisation
US5247085A (en) * 1987-11-30 1993-09-21 Beecham Group P.L.C. Antiviral purine compounds
WO1995024410A1 (fr) * 1994-03-08 1995-09-14 Otsuka Pharmaceutical Factory, Inc. Derive de diester phosphonique
WO1998017672A1 (fr) * 1996-10-24 1998-04-30 Novartis Ag Acides aminoalcanophosphoniques substitues

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8318700B2 (en) 2004-12-16 2012-11-27 The Regents Of The University Of California Lung-targeted drugs
US8101745B2 (en) 2004-12-16 2012-01-24 The Regents Of The University Of California Lung-targeted drugs
US10449207B2 (en) 2013-03-15 2019-10-22 The Regents Of The University Of California Acyclic nucleoside phosphonate diesters
US9775852B2 (en) 2013-03-15 2017-10-03 The Regents Of The University Of California Acyclic nucleoside phosphonate diesters
US10076533B2 (en) 2013-03-15 2018-09-18 The Regents Of The University Of California Acyclic nucleoside phosphonate diesters
US10076532B2 (en) 2013-03-15 2018-09-18 The Regents Of The University Of California Acyclic nucleoside phosphonate diesters
US10195222B2 (en) 2013-03-15 2019-02-05 The Regents Of The University Of California Acyclic nucleoside phosphonate diesters
US11344555B2 (en) 2014-09-15 2022-05-31 The Regents Of The University Of California Nucleotide analogs
US10213430B2 (en) 2014-09-15 2019-02-26 The Regents Of The University Of California Nucleotide analogs
US10702532B2 (en) 2014-09-15 2020-07-07 The Regents Of The University Of California Nucleotide analogs
US9801884B2 (en) 2014-09-15 2017-10-31 The Regents Of The University Of California Nucleotide analogs
US12350274B2 (en) 2014-09-15 2025-07-08 The Regents Of The University Of California Nucleotide analogs
US10377782B2 (en) 2015-09-15 2019-08-13 The Regents Of The University Of California Nucleotide analogs
US11014950B2 (en) 2015-09-15 2021-05-25 The Regents Of The University Of California Nucleotide analogs
US11572377B2 (en) 2015-09-15 2023-02-07 The Regents Of The University Of California Nucleotide analogs
US12329768B2 (en) 2022-07-21 2025-06-17 Antiva Biosciences, Inc. Compositions and dosage forms for treatment of HPV infection and HPV-induced neoplasia

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Publication number Publication date
AU2645199A (en) 2000-06-05

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