EP1472229A1 - Heterocycles pentagonaux utilises en tant qu'agents antiviraux - Google Patents

Heterocycles pentagonaux utilises en tant qu'agents antiviraux

Info

Publication number
EP1472229A1
EP1472229A1 EP03734671A EP03734671A EP1472229A1 EP 1472229 A1 EP1472229 A1 EP 1472229A1 EP 03734671 A EP03734671 A EP 03734671A EP 03734671 A EP03734671 A EP 03734671A EP 1472229 A1 EP1472229 A1 EP 1472229A1
Authority
EP
European Patent Office
Prior art keywords
alkyl
group
alkoxy
substituted
optionally
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Withdrawn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
EP03734671A
Other languages
German (de)
English (en)
Inventor
Tobias Wunberg
Ulrich Betz
Gerald Kleymann
Susanne Nikolic
Jürgen Reefschläger
Rudolf Schohe-Loop
Holger Zimmermann
Franz Zumpe
Wolfgang Bender
Kerstin Henninger
Guy Hewlett
Axel Jensen
Jörg Keldenich
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.)
Bayer AG
Original Assignee
Bayer Healthcare AG
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 Bayer Healthcare AG filed Critical Bayer Healthcare AG
Publication of EP1472229A1 publication Critical patent/EP1472229A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
    • C07D249/12—Oxygen or sulfur atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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
    • C07D231/14—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 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
    • C07D231/18—One oxygen or sulfur atom
    • C07D231/20—One oxygen atom attached in position 3 or 5
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems

Definitions

  • the invention relates to 5-ring heterocycles and processes for their preparation and their use for the manufacture of medicaments for the treatment and / or prophylaxis of diseases, in particular for use as antiviral agents, in particular against cytomegaloviruses.
  • EP-A-8391 describes benzimidazole substituted pyridazinones for cardiovascular diseases and with antiviral activity.
  • R 4 represents Ci-C ⁇ -alkyl, where alkyl can optionally be substituted with up to three substituents independently of one another selected from the group consisting of hydroxy, C 6 -C 10 aryl, C 1 -C 6 alkoxy, amino, C 1 - C 6 alkyl amino, C ö alkylcarbonylamino, hydroxy-carbonyl, C ⁇ -C 6 alkoxycarbonyl and C ⁇ -C 6 -AlkylarrrinocarbonyL
  • R 5 for hydrogen, halogen, hydroxy, Ci-C 6 -alkoxy, amino, Ci-C 6 -
  • Cycloalkyl stands for a cycloalkyl group with generally 3 to 8, preferably 5 to 7 carbon atoms, by way of example and preferably for cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and adamantyl.
  • Aryl is an example of a mono- to tricyclic aromatic, carbocyclic radical with generally 6 to 14 colile atoms and preferably phenyl, naphthyl and phenanthrenyl.
  • R and R together with the carbon atom to which they are attached form a C 5 -C 6 cycloalkyl ring
  • R 6 is isopropyl, cyclohexyl or 1-phenylethyl.
  • NO 2 is bound to the aromatics via one of the positions 2, 3, 5 or 6, and
  • R 3 has the meaning given above, are implemented.
  • the reaction takes place in inert solvents, preferably in a temperature range from room temperature to the reflux of the solvents at normal pressure.
  • Toluene, hexane, cyclohexane or petroleum fractions, or other solvents such as dimethylformamide, dimethylacetamide, acetonitrile or pyridine, ethanol or isopropanol are preferred.
  • NO is bound to the aromatics via one of the positions 2, 3, 5 or 6, and
  • R 5 has the meaning given above
  • NHC (O) CH 3 is bonded to the aromatics via one of the positions 2, 3, 5 or 6, and
  • R 3 and R 5 have the meaning given above
  • NHC (O) CH 3 is bonded to the aromatics via one of the positions 2, 3, 5 or 6, and
  • the active substance can act systemically and / or locally.
  • it can be applied in a suitable way, e.g. oral, parenteral, pulmonal, nasal, sublingual, lingual, buccal, rectal, transdermal, cojunctival, otic or as an implant.
  • Inhaled drug forms e.g. powder inhalers, nebulizers
  • nasal drops / solutions, sprays e.g., nasal drops / solutions, sprays; tablets or capsules to be administered lingually, sublingually or buccally, suppositories, ear and eye preparations, vaginal capsules, aqueous suspensions (lotions, shaking mixtures), lipophilic suspensions, ointments, creams, milk, pastes, powder or
  • 3iJ-pyrazol-3-one are obtained with 3.61 g (16 mmol) of tin dichloride dihydrate and 758 mg (84% of theory) of product.
  • CC 50 (NHDF) substance concentration in ⁇ M at which no visible cytostatic effects on the cells can be seen compared to the untreated cell control
  • EC 50 (HCMV) substance concentration in ⁇ M that inhibits the CPE (cytopathic effect) by 50% compared to the untreated virus control
  • SI selectiveivity index
  • the compounds according to the invention can be converted into pharmaceutical preparations as follows:
  • the mixture of active ingredient, lactose and starch is granulated with a 5% solution (m / m) of the PVP in water.
  • the granules are dried with the magnesium stearate for 5 min. mixed.
  • This mixture is compressed with a conventional tablet press (tablet format see above).
  • a pressure force of 15 kN is used as a guideline for the pressing.
  • Rhodigel is suspended in ethanol, the active ingredient is added to the suspension. The water is added with stirring. The swelling of the Rhodigel is stirred for about 6 hours.

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Virology (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Communicable Diseases (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention se rapporte à des hétérocycles pentagonaux, à leur procédé de production ainsi qu'à leur utilisation pour produire des médicaments servant à traiter et/ou prévenir des maladies, et en particulier à leur utilisation en tant qu'agents antiviraux, en particulier contre des cytomégalovirus.
EP03734671A 2002-01-28 2003-01-16 Heterocycles pentagonaux utilises en tant qu'agents antiviraux Withdrawn EP1472229A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10203086 2002-01-28
DE10203086A DE10203086A1 (de) 2002-01-28 2002-01-28 5-Ring Heterozyklen
PCT/EP2003/000376 WO2003064394A1 (fr) 2002-01-28 2003-01-16 Heterocycles pentagonaux utilises en tant qu'agents antiviraux

Publications (1)

Publication Number Publication Date
EP1472229A1 true EP1472229A1 (fr) 2004-11-03

Family

ID=7713161

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03734671A Withdrawn EP1472229A1 (fr) 2002-01-28 2003-01-16 Heterocycles pentagonaux utilises en tant qu'agents antiviraux

Country Status (6)

Country Link
EP (1) EP1472229A1 (fr)
JP (1) JP2005521669A (fr)
AU (1) AU2003239243A1 (fr)
CA (1) CA2474456A1 (fr)
DE (1) DE10203086A1 (fr)
WO (1) WO2003064394A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT1797037E (pt) * 2004-09-29 2015-03-17 Bayer Healthcare Llc Processo para a preparação de 4-{4-[({[4-cloro-3- (trifluorometil)-fenil]-amino}-carbonil)-amino]-fenoxi}-nmetilpiridina- 2-carboxamida
WO2014130582A2 (fr) * 2013-02-19 2014-08-28 Senomyx, Inc. Composés utiles comme modulateurs de trpm8

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES482789A0 (es) * 1978-08-25 1980-12-01 Thomae Gmbh Dr K Procedimiento para la preparacion de nuevos bencimidazoles sustituidos en posicion 5 o 6 con un anillo de piridazinona
WO1997021707A1 (fr) * 1995-12-14 1997-06-19 Merck & Co., Inc. Antagonistes de la gonadoliberine
JP2001526222A (ja) * 1997-12-22 2001-12-18 バイエル コーポレイション アリールおよびヘテロアリール置換複素環尿素を使用するｐ３８キナーゼ活性の阻害

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO03064394A1 *

Also Published As

Publication number Publication date
WO2003064394A1 (fr) 2003-08-07
JP2005521669A (ja) 2005-07-21
DE10203086A1 (de) 2003-07-31
AU2003239243A1 (en) 2003-09-02
CA2474456A1 (fr) 2003-08-07
WO2003064394A8 (fr) 2003-12-24

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