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WO2000068186A1 - Bis-sulfonamide a action anti-hcmv - Google Patents

Bis-sulfonamide a action anti-hcmv Download PDF

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Publication number
WO2000068186A1
WO2000068186A1 PCT/EP2000/003687 EP0003687W WO0068186A1 WO 2000068186 A1 WO2000068186 A1 WO 2000068186A1 EP 0003687 W EP0003687 W EP 0003687W WO 0068186 A1 WO0068186 A1 WO 0068186A1
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WO
WIPO (PCT)
Prior art keywords
alkyl
substituted
group
optionally
hydroxy
Prior art date
Application number
PCT/EP2000/003687
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German (de)
English (en)
Inventor
Siegfried Goldmann
Wolfgang Bender
Jürgen Reefschläger
Peter Eckenberg
Michael Härter
Sabine Hallenberger
Jörg TRAPPE
Olaf Weber
Original Assignee
Bayer Aktiengesellschaft
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 Aktiengesellschaft filed Critical Bayer Aktiengesellschaft
Priority to AU45557/00A priority Critical patent/AU4555700A/en
Publication of WO2000068186A1 publication Critical patent/WO2000068186A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
    • C07D295/26—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
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
    • C07D211/96—Sulfur atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring

Definitions

  • the present invention relates to new compounds which are suitable as medicaments, processes for their preparation and their use as medicaments, in particular as antiviral agents.
  • ⁇ , ⁇ -Naphthyl linked phenylsulfonamides are mainly known from phototechnical publications [see see JP-06 122 669-A2, EP-684 515-A1; JP-59 174 836-A2, DE-2 902 074, US-3 925 347, US-4 035 401, US-3 622 603, US-3 482 971. EP-284 130].
  • WO 90/09 787 discloses sulfonamides as radio- or chemosensitizers and their use in the treatment of tumors.
  • the invention relates to compounds of the general formula (I):
  • R represents hydrogen or a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon group with 1 to 14 carbon atoms, in which case one or two carbon atoms in the chain can optionally be replaced by O or S, and which can be substituted by one to three substituents, which are selected from the group consisting of hydroxy, cyano, -N (R 6 ) R 7 , (C, -C 6 ) alkoxycarbonyl, (C 6 -C 10 ) Nryl and 5- to 10-glie- drigem heteroaryl, where (C 6 -C ⁇ o) aryl and 5- to 10-membered heteroaryl may in turn be substituted by one to three substituents consisting of hydroxy, (GC 6 ) alkyl, (C ⁇ -C 6 ) alkoxy, (GC 6 ) -alkoxycarbonyl, halogen and halogen (-C-C 6 ) alkyl are selected, and wherein
  • R 6 and R 7 are the same or different and represent hydrogen, (C- . -C 6 ) alkoxycarbonyl or a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon group with 1 to 10 carbon atoms, optionally with di (C ⁇ - C 6 ) alkylamino is substituted, or together with the nitrogen atom to which they are attached form a 3- to 8-membered heterocyclic ring which can optionally be substituted by 1 to 3 (GC 6 ) alkyl groups and or or or can contain two further heteroatoms selected from O, S or N,
  • R 1 represents (C 6 -C ⁇ o) aryl or 5- to 10-membered heteroaryl, which can optionally be substituted by one to three substituents n, which are selected from the group consisting of (C - C 6 ) alkyl , Hydroxy, (GC 6 ) alkoxycarbonyl, halogen and amino, or
  • R stands for (-CC 6 ) alkoxy, (Cr C 6 ) alkoxycarbonyl, aminocarbonyl or may have one of the meanings of R mentioned above and may be the same or different from this meaning,
  • R and R together with the nitrogen atom to which they are attached form a saturated or unsaturated ring with up to 14 carbon atoms
  • R 8 represents hydrogen, a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon group having up to 10 carbon atoms, which may be selected by 1 to 3 radicals from the group consisting of hydroxyl, pyrrolidinyl, pyridyl, phenyl, halophenyl, halogen (-C-C 3 ) alkylphenyl and (-C-C 6 ) alkoxycarbonyl exists, can be substituted,
  • Heteroaryl is where (C6-C ⁇ o) aryl and 5- to 10-membered heteroaryl can in turn be substituted by one to three substituents which are selected from the group consisting of halogen, hydroxy, (CC 6 ) alkoxy, nitro and fluorine (CC 3 ) alkyl, R 3 represents hydrogen, halogen, hydroxy, (GC 6 ) acyl, benzoyl or (GC 6 ) acyloxy,
  • R 4 and R 5 are independently a (GC 3 ) alkyl group or together with the carbon atom to which they are attached form a 3- to 6-membered carbocyclic ring,
  • A is a divalent (C 6 -C 1 o) aryl radical or a divalent 5- to 10-membered heteroaryl radical which may be optionally substituted by one to three substituents selected from the group consisting of (C * -C 3 ) Alkyl, hydroxy or halogen atoms, and
  • D and E are the same or different and represent hydrogen, fluorine, chlorine, nitro, cyano, hydroxy or (GC 3 ) alkyl (GC 3 ) alkoxy or (C, -C 3 ) alkoxycarbonyl,
  • the substances according to the invention can also be present as salts.
  • Physiologically acceptable salts are preferred in the context of the invention.
  • Physiologically acceptable salts can be salts of the compounds according to the invention with inorganic or organic acids.
  • Salts with inorganic acids such as, for example, hydrochloric acid, hydrobromic acid, phosphoric acid or sulfuric acid, or salts with organic carboxylic or sulfonic acids such as, for example, acetic acid, maleic acid, fumaric acid, malic acid, citric acid, tartaric acid, lactic acid, benzoic acid, or methanesulfonic acid, ethanesulfonic acid, phenylsulfonic acid , Toluenesulfonic acid or naphthalenedisulfonic acid.
  • Physiologically acceptable salts can also be metal or ammonium salts of the compounds according to the invention. Particularly preferred are, for example, sodium, potassium, magnesium or calcium salts, and also ammonium salts which are derived from ammonia, or organic amines, such as, for example, ethylamine, di- or triethylamine, di- or triethanolamine, dicyclohexylamine, dimethylaminoethanol, Arginine, lysine, ethylenediamine or 2-phenylethylamine.
  • ammonium salts which are derived from ammonia, or organic amines, such as, for example, ethylamine, di- or triethylamine, di- or triethanolamine, dicyclohexylamine, dimethylaminoethanol, Arginine, lysine, ethylenediamine or 2-phenylethylamine.
  • the compounds of the general formula (I) according to the invention can occur in various stereochemical forms which either behave like images and mirror images (enantiomers) or do not behave like images and mirror images (diastereomers).
  • the invention relates to both the antipodes and the racemic forms as well as the diastereomer mixtures. Like the diastereomers, the racemic forms can be separated into the stereoisomerically uniform constituents in a known manner.
  • a straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon group having 1 to 14 carbon atoms includes, for example, a straight-chain or branched alkyl radical having 1 to 14 carbon atoms, a straight-chain or branched alkenyl radical having 2 to 14 carbon atoms, a straight-chain or branched Alkynyl radical with 2 to 14 carbon atoms and a saturated or unsaturated cyclic hydrocarbon radical with 3 to 6 carbon atoms in the definition of R 1 .
  • radicals in which 1 to 2 carbon atoms of the abovementioned hydrocarbon groups in the chain can be replaced by O or S, for example (C 1 -C 6) alkoxyalkyl, (C 1 -C 6) alkylthioalkyl radicals.
  • straight-chain or branched alkyl group with 1 to 14 carbon atoms examples may be mentioned: methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, isopentyl, hexyl, isohexyl, heptyl, isoheptyl, octyl, nonyl, decyl, Undecyl and dodecyl.
  • straight-chain or branched alkenyl groups with 2 to 14 carbon atoms are: allyl, propenyl, isopropenyl, butenyl, isobutenyl, pentenyl, isopentenyl, hexenyl, isohexenyl, heptenyl, isoheptenyl, octenyl and isooctenyl.
  • alkynyl group having 2 to 14 carbon atoms straight-chain or branched radicals can be mentioned which have one or more ClustC groups.
  • Alkynyl radicals having 2 to 8 carbon atoms are preferred and, for example, acetylenyl, 2-butynyl, 2-pentynyl and 2-hexynyl may be mentioned.
  • cycloalkyl group having 3 to 6 carbon atoms includes, for example, cyclopropyl, cyclopentyl and cyclohexyl. Cyclopropyl is preferred.
  • the straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon group having 1 to 14 carbon atoms in the definition of R 1 is preferably a straight-chain alkyl group having 1 to 12 carbon atoms or a (C i -C 6 ) alkoxy (C i -C6) alkyl group.
  • (-C -Cg) alkyl in the context of the invention generally represents straight-chain or branched-chain hydrocarbon radicals having 1 to 6 carbon atoms, and in this regard reference is made to the groups mentioned by way of example in the explanations for the alkyl group having 1 to 14 carbon atoms above.
  • the (C ⁇ -C6) alkoxy group as used in the present invention, and as they also in the definitions (C ⁇ -C6) alkoxycarbonyl, (C ⁇ -Cö) alkoxycarbonyl (C ⁇ -Cö) alkyl and (C ⁇ -C6 ) Alkoxycarbonylamino used includes, for example, straight-chain or branched-chain alkoxy groups having 1 to 6 carbon atoms, particularly preferably alkoxy groups having 1 to 4 carbon atoms, more preferably alkoxy groups having 1 to 3 carbon atoms.
  • methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentoxy, isopentoxy, hexoxy and isohexoxy can be mentioned.
  • Methoxy, ethoxy and propoxy are preferred.
  • the straight chain, branched or cyclic, saturated or unsaturated hydrocarbon group with 1 to 10 carbon atoms in the definition of R ⁇ and R ⁇ includes, for example, the above for the definition of the straight chain, branched chain or cyclic, saturated or unsaturated hydrocarbon groups with 1 to 14 carbon atoms in the definition of Rl groups with 1 to 10 carbon atoms.
  • a straight-chain or branched-chain (Ci-Cg) alkyl group is preferred here.
  • (C 1 -C 6) alkylamino includes the alkylamino groups whose alkyl groups have 1 to 6 carbon atoms. These can be symmetrical or asymmetrical alkylamino groups, such as dimethylamino, diethylamino, methyl, ethylamino, etc.
  • R6 and R * * 7 can form together with the nitrogen atom to which they are attached include, for example, pyrrolidine, piperidine, morpholine etc.
  • (Cg-C ⁇ o) aryl stands for an aromatic radical having 6 to 10 carbon atoms.
  • Preferred aryl radicals are phenyl and naphthyl. 5- to
  • 10-membered heteroaryl is 5- to 10-membered Rings containing heteroatoms, which can contain 1 to 4 heteroatoms, which are selected from O, S and N and include, for example, pyridyl, furyl, thienyl, pyrolyl, imidazolyl, pyrazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolinizyl, indolyl, benzo [b] thienyl, indazolyl, quinolyl, isoquinolyl, naphthyridinyl, quinazolinyl, etc.
  • Halogen in the context of the invention includes fluorine, chlorine, bromine and iodine. Chlorine or fluorine are preferred.
  • Halogen (C 1 -C 6) alkyl in the context of the invention includes (C 1 -C 6) alkyl groups, as defined above, which can be substituted by 1 to 3 halogen atoms, preferably fluorine or chlorine, such as monofluoroalkyl groups having 1 to 3
  • alkyl groups reference is made to the above explanations.
  • Fluoromethyl, chloromethyl and trifluoromethyl are particularly preferred.
  • R8 is referred to the above-mentioned definition of straight-chain, branched or cyclic, saturated or unsaturated hydrocarbon groups with 1 to 10 carbon atoms in the definition of R "and R.
  • fluoro (C 3 -C 3) alkyl includes alkyl groups with 1 to 3
  • Carbon atoms with up to 3 fluorine atoms such as Trifluoromethyl.
  • hydroxy (C 1 -C 6) alkyl includes the above-mentioned straight-chain or branched-chain alkyl groups having 1 to 6 carbon atoms, which can be substituted by 1 to 3 hydroxyl groups. Hydroxy-methyl is preferred.
  • (C 1 -C 6) acyl and (C 1 -C) acyl in the definition (C 1 -C 6) acyloxy stand for straight-chain or branched-chain alkanoyl with 1 to 6 carbon atoms. Examples include: formyl, acetyl, propanoyl,
  • the invention includes compounds of general formula (I) above, wherein:
  • Rl stands for hydrogen, a (Cß-Cß ⁇ cycloalkyl group, a (C2-Cö) alkenyl group or a straight-chain or branched-chain (Cj-C 12) - alkyl group, in which a chain carbon atom is optionally replaced by oxygen, and the may optionally be substituted by 1 to 3 substituents selected from the group consisting of hydroxy, cyano,
  • R6 and R 7 are the same or different and represent hydrogen, (Ci -Cß) -
  • Rl represents phenyl or 5- to 10-membered heteroaryl, which may contain 1 to 2 heteroatoms selected from nitrogen and sulfur, each optionally with 1 to 2 substituents selected from amino, (C1 -C3) -
  • Alkyl, hydroxy, (-C-C4) alkoxycarbonyl and halogen may be substituted, or
  • R2 stands for (C 1 -C 6) alkyl, (C 5 -C 6) alkoxy, and aminocarbonyl, or can have the abovementioned meaning of R 1 and can be identical or different from this meaning, or
  • Alkyl group which can optionally be selected by 1 to 2 substituents, which can be substituted from the group consisting of
  • R8 stands for (C3-C6) cycloalkyl or phenyl, which can optionally be substituted with 1 to 3 substituents selected from the group consisting of halogen, hydroxy, (C 1 -C 3) alkoxy, nitro and trifluoromethyl, or
  • R8 represents pyridyl or (Ci-Cg) alkoxycarbonyl
  • R3 represents hydrogen, halogen, hydroxy or (Ci -C3) acyloxy
  • R ⁇ and R-5 each independently represent a (C1-C3) alkyl group
  • A represents a naphthalenediyl radical or a phenylene radical, which may optionally be substituted by a (C 3 -C 3) alkyl group, halogen or hydroxy, and
  • D and E represent hydrogen, and their pharmaceutically acceptable salts.
  • the invention includes compounds of the above formula (I), in which
  • Rl represents hydrogen, cyclopropyl, or a straight-chain or branched-chain (Ci-C3) alkyl group
  • Rl represents phenyl, which may optionally be substituted by hydroxy
  • R 2 represents hydrogen or (C 3 -C 3) alkyl
  • Rl and R2 together with the nitrogen atom to which they are attached form a ring which is selected from the group consisting of morpholino, which may optionally be substituted by 1 to 3 (C1-C3) alkyl groups,
  • a 5- to 8-membered saturated ring in which a ring carbon atom can optionally be replaced by a group of the formula -NR 8 , wherein
  • R is selected from hydrogen, (C1-C3) alkyl, which can optionally be substituted by phenyl, phenyl and cyclopropyl, and which is optionally selected from 1 to 2 substituents from oxo, (-C -Czi) alkanoyl, phenyl, which is optionally replaced by ( Cj-C- ⁇ alkoxy may be substituted, benzoyl may be substituted, R ⁇ represents hydrogen, chlorine, fluorine or acetyloxy,
  • R 4 and R 5 represent methyl
  • A represents naphthalene-1, 5-diyl or 1,3-phenylene, which is optionally by
  • Chlorine or fluorine may be substituted, and wherein
  • the invention includes compounds of the following formula (V):
  • R 1 , R 2 , R 3 , R 4 , R 5 and A are as defined above.
  • the invention includes compounds of formula (I) or (F), wherein A is naphthalenediyl.
  • the invention includes compounds of formula (I) or (I '), wherein
  • R3 represents hydrogen or halogen
  • R 4 and R ⁇ each represent a methyl group
  • A represents a phenylene or naphthalenediyl radical
  • the invention further relates to a process for the preparation of compounds of the general formula (I) or (V) (the compounds of the general formula (I) include the compounds of the general formula (F)), characterized in that compounds of the general formula (II)
  • the usual inert solvents which do not change under the reaction conditions are suitable as solvents for all process steps.
  • These preferably include organic solvents such as ethers e.g. Diethyl ether, glycol mono- or dimethyl ether, dioxane or tetrahydrofuran, or hydrocarbons such as benzene, toluene, xylene, cyclohexane or petroleum fractions or halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, or dimethylsulfoxide, dimethylformamide, hexamethylphosphoric acid triamidine, triamidine, triamidine, or trisaminophenamide,. It is also possible to use mixtures of the solvents mentioned, if appropriate also with water. Methylene chloride, tetrahydrofuran, pyridine and dioxane are particularly preferred.
  • Suitable bases are organic amines, in particular trialkyl (C 1 -C 6 ) amines such as triethylamine or heterocycles such as pyridine, methylpiperidine, piperidine or N-methylmorpholine. Pyridine, triethylamine and N-methylmorpholine are preferred.
  • the reactions can be carried out under normal pressure, but also under elevated or reduced pressure (for example 0.5 to 3 bar). Generally one works at normal pressure.
  • the reactions are carried out in a temperature range from 0 ° C. to 100 ° C., preferably at 0 ° C. to 30 ° C. and under normal pressure.
  • the invention further relates to compounds of formula (I) or (1 ') for use as a medicament.
  • the invention further relates to a pharmaceutical composition which comprises a compound of the general formula (I) or (F) in a mixture with at least one pharmaceutically acceptable carrier or excipient.
  • the invention further relates to the use of the compound of the general
  • the invention further relates to the use of a compound of the general formula (I) or (F) for the manufacture of a medicament for the treatment of viral infections, in particular infections by cytomegaloviruses.
  • the compounds of general formulas (I) according to the invention show an unpredictable surprising spectrum of action. They show an antiviral activity against representatives of the group of herpes viridae, especially against the human cytomegalovirus (HCMV). They are therefore suitable for treatment and
  • HCMV human cytomegalovirus
  • the anti-HCMV activity was determined in a screening test system in 96-well microtiter plates with the aid of human embryonic lung fibroblasts
  • HELF HELF cell cultures
  • the compounds according to the invention are therefore valuable active substances for the treatment and prophylaxis of diseases which are triggered by human cytomegalovirus.
  • the following areas of indication can be mentioned, for example:
  • HCMV infections Treatment and prophylaxis of HCMV infections in AIDS patients (retinitis, pneumonitis, gastrointestinal infections).
  • mice 5 week old male mice, strain NOD / LtSz-Prkdc (scid) / J, were obtained from a commercial breeder (The Jackson Lab., Bar Harbor). The animals were kept in isolators under sterile conditions (including bedding and feed).
  • Murine cytomegalovirus (MCMV), Smith strain, was passaged in vivo (BALB / c) and purified by fractional centrifugation. The titer was checked using a plaque assay on primary embryonic mouse fibroblasts. is looking for. The mice were infected with a dose of 5 ⁇ 10 5 pfu in a total volume of 0.2 ml intraperitoneally. This dose leads to death in 100% of the infected animals after approx. 11 days.
  • mice 24 hours after infection, the mice were treated with substance orally twice daily (morning and evening) over a period of 8 days.
  • the dose was 25 mg / kg body mass, the application volume 10 ml / kg body mass.
  • the substances were formulated in the form of a 0.5% tylose suspension. 16 hours after the last substance application, the animals were killed painlessly and the salivary gland, liver and kidney were removed.
  • the purity of the DNA was checked using the quotient OD 260 / OD 280 and the DNA was then adjusted with Tris-EDTA pH - 8.0.
  • the MCMV-DNA was quantified by means of DNA dot blot hybridization.
  • a digoxygenin-labeled (Boehringer-Mannheim, also listed buffer, unless otherwise described) 1.2 kb fragment from the MCMV range, Smith, Hindlll J, was used as the probe.
  • the signals were detected by means of chemiluminescence. For this, the membrane was washed in 1 x digoxygenin wash buffer 1 for 3 minutes. The filters were then used for 30
  • the new active compounds can be converted in a known manner into the customary formulations, such as tablets, dragées, pills, granules, aerosols, syrups, emulsions, suspensions and solutions, using inert, non-toxic, pharmaceutically suitable excipients or solvents.
  • the therapeutically active compound should in each case be present in a concentration of about 0.5 to 90% by weight of the total mixture, i.e. in amounts sufficient to achieve the dosage range indicated.
  • the formulations are prepared, for example, by stretching the active ingredients with solvents and / or carriers, optionally using emulsifiers and / or dispersants, e.g. if water is used as a diluent, organic solvents can optionally be used as auxiliary solvents.
  • the application is carried out in the usual way, preferably orally, parenterally or topically, in particular perlingually, intravenously or intravitreally, optionally as a depot in an implant.
  • solutions of the active ingredients can be used using suitable liquid carrier materials.

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  • Organic Chemistry (AREA)
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Abstract

L'invention concerne des composés de formule (I) dans laquelle A, D, E et R1-R5 ont les significations données dans la description, ainsi qu'un procédé pour leur fabrication et leur utilisation comme médicaments, en particulier comme agents antiviraux, notamment vis-à-vis de cytomégalovirus humain.
PCT/EP2000/003687 1999-05-06 2000-04-25 Bis-sulfonamide a action anti-hcmv WO2000068186A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU45557/00A AU4555700A (en) 1999-05-06 2000-04-25 Bis-sulfonamide with anti-hcmv effect

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19920790A DE19920790A1 (de) 1999-05-06 1999-05-06 Bis-Sulfonamide mit anti-HCMV-Wirkung
DE19920790.9 1999-05-06

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WO2000068186A1 true WO2000068186A1 (fr) 2000-11-16

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US9266892B2 (en) 2012-12-19 2016-02-23 Incyte Holdings Corporation Fused pyrazoles as FGFR inhibitors
US9388185B2 (en) 2012-08-10 2016-07-12 Incyte Holdings Corporation Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors
US9533954B2 (en) 2010-12-22 2017-01-03 Incyte Corporation Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3
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US9580423B2 (en) 2015-02-20 2017-02-28 Incyte Corporation Bicyclic heterocycles as FGFR4 inhibitors
US9611267B2 (en) 2012-06-13 2017-04-04 Incyte Holdings Corporation Substituted tricyclic compounds as FGFR inhibitors
US9708318B2 (en) 2015-02-20 2017-07-18 Incyte Corporation Bicyclic heterocycles as FGFR4 inhibitors
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US12012409B2 (en) 2020-01-15 2024-06-18 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
US12065494B2 (en) 2021-04-12 2024-08-20 Incyte Corporation Combination therapy comprising an FGFR inhibitor and a Nectin-4 targeting agent
US12122767B2 (en) 2019-10-01 2024-10-22 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
US12428420B2 (en) 2021-06-09 2025-09-30 Incyte Corporation Tricyclic heterocycles as FGFR inhibitors

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060276464A1 (en) * 2005-05-13 2006-12-07 Wyeth Diarylsulfone sulfonamides and use thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999037609A1 (fr) * 1998-01-23 1999-07-29 Bayer Aktiengesellschaft Nouveaux sulfamides a substitution par naphtyle et anilide
DE19802436A1 (de) * 1998-01-23 1999-07-29 Bayer Ag Neue Naphthyl- und heterocyclisch-substituierte Sulfonamide
DE19802437A1 (de) * 1998-01-23 1999-07-29 Bayer Ag Verwendung von substituierten Sulfonamiden als anitvirale Mittel und neue Stoffe

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999037609A1 (fr) * 1998-01-23 1999-07-29 Bayer Aktiengesellschaft Nouveaux sulfamides a substitution par naphtyle et anilide
DE19802436A1 (de) * 1998-01-23 1999-07-29 Bayer Ag Neue Naphthyl- und heterocyclisch-substituierte Sulfonamide
DE19802437A1 (de) * 1998-01-23 1999-07-29 Bayer Ag Verwendung von substituierten Sulfonamiden als anitvirale Mittel und neue Stoffe

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