WO2006131340A2 - Inhibiteurs de la peptide deformylase (pdf) 3 - Google Patents

Inhibiteurs de la peptide deformylase (pdf) 3 Download PDF

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WO2006131340A2
WO2006131340A2 PCT/EP2006/005429 EP2006005429W WO2006131340A2 WO 2006131340 A2 WO2006131340 A2 WO 2006131340A2 EP 2006005429 W EP2006005429 W EP 2006005429W WO 2006131340 A2 WO2006131340 A2 WO 2006131340A2
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group
alkyl
cycloalkyl
heterocycloalkyl
heteroalkyl
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PCT/EP2006/005429
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WO2006131340A3 (fr
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Michael Thormann
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Origenis Ag
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/273—2-Pyrrolidones 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 other ring carbon 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
    • A61P31/04—Antibacterial agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
    • C07D207/36—Oxygen or sulfur atoms
    • C07D207/38—2-Pyrrolones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the present invention relates to novel inhibitors of peptide deformylase (PDF). These compounds are of particular interest as antibiotics, anticancer drugs, antiparasitics and herbicides.
  • PDF peptide deformylase
  • Peptide deformylase is a metalloenzyme, depending on
  • Organism contains iron or zinc in the active center. Analyzes at the genome level have shown that in addition to bacteria, parasites, plants (Giglione et al., EMBO J. 19 (21): 5916-5929 (2000)) and mammals also contain peptide deformylase. The enzyme is detectable in prokaryotes and in organelles of eukaryotes and plays a vital role in protein metabolism (Lee et al., J. Clin. Invest. 114: 1107-1116 (2004)). Peptide deformylase catalyzes the removal of the formyl group from the N-terminus of N-formylated proteins in a post-translational modification. Without the enzyme peptide deformylase, fully functional proteins can not be produced. Peptide deformylase is the target of a new class of antibiotics, anticancer drugs, antiparasitics and herbicides called peptide deformylase inhibitors.
  • the aim of the present invention was to provide novel inhibitors of peptide deformylase which are synthetically accessible by a simple route.
  • the present invention relates to compounds of the formula (D, wherein
  • R 1 and R 2 independently of one another represent a hydrogen atom, an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaryl radical; aralkyl group, or Ri and R 2 together are part of an optionally substituted cycloalkyl ring or heterocycloalkyl ring having preferably 3 to 8 ring atoms;
  • R 3 is a hydrogen atom, an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
  • R 4 is a hydrogen atom, an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical, or R 3 and R 4 together Part of an optionally substituted cycloalkyl or heterocycloalkyl ring having preferably 3 to 8 ring atoms;
  • R 5 is a hydrogen atom, a halogen atom, an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
  • R 6 is a hydrogen atom, an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
  • R 7 is a hydrogen atom, an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
  • X is a group of formula -CH 2 -NOH-CHS, -NOH-CHS, -NOH-CHO, -CH 2 -NOH-CHO, -CH 2 -CHOH-CHO or -CHOH-CHO- or is selected from the following formulas :
  • U is a bond, CH 2 , NH, O or S
  • V is 0, S, NH or CH 2
  • W is 0, S, NH or CH 2
  • Y is OH or NH 2
  • E is a bond , CH 2 , NH, O or S is and the groups D, G and M independently of one another are N or CH, it being possible for all the above radicals to be optionally substituted,
  • alkyl refers to a saturated, straight-chain or branched hydrocarbon group having in particular 1 to 20 carbon atoms, preferably 1 to 12 carbon atoms, more preferably 1 to 6 carbon atoms, e.g. the methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-hexyl, 2, 2-dimethylbutyl or n-octyl group.
  • alkenyl and alkynyl refer to at least partially unsaturated, straight-chain or branched hydrocarbon groups having in particular 2 to 20 carbon atoms, preferably 2 to 12 carbon atoms, more preferably 2 to 6 carbon atoms, e.g. the ethenyl, allyl, acetylenyl, propargyl, isoprenyl or hex-2-enyl group.
  • Alkenyl groups preferably have one or two (particularly preferably one) double bonds or alkinyl groups one or two (particularly preferably one) triple bonds.
  • heteroalkyl refers to an alkyl, an alkenyl or an alkynyl group in which one or more (preferably 1, 2 or 3) carbon atoms are represented by an oxygen, nitrogen, phosphorus, boron, selenium, Silicon or sulfur atom are replaced (preferably oxygen, sulfur or nitrogen).
  • heteroalkyl further refers to a carboxylic acid or a carboxylic acid derived group such as acyl, acylalkyl, alkoxycarbonyl, acyloxy, acyloxyalkyl, carboxyalkylamide or alkoxycarbonyloxy.
  • R d is a hydrogen atom, a Ci-C ⁇ - alkyl, C 2 -C 6 alkenyl or a C 2 -C 6 alkynyl group and Y a is a direct bond, a Ci-C ß -alkylene, C2 C 6 is alkenylene or a C 2 -C 6 alkynylene group, each of
  • Heteroalkyl group contains at least one carbon atom and one or more hydrogen atoms may be replaced by fluorine or chlorine atoms.
  • Heteroalkyl groups are methoxy, trifluoromethoxy, ethoxy, n-propyloxy, isopropoxy, tert-butyloxy, methoxymethyl, ethoxymethyl, methoxyethyl, methylamino, ethylamino, dimethylamino, diethylamino, isopropylamino, methylaminomethyl, ethylaminomethyl, diisopropylaminoethyl,
  • Enol ethers dimethylaminomethyl, dimethylaminoethyl, acetyl, propionyl, butyryloxy, acetyloxy, methoxycarbonyl, ethoxycarbonyl, N-ethyl-N-methylcarbamoyl or N-methylcarbamoyl.
  • heteroalkyl groups are nitrile, isonitrile, cyanate, thiocyanate, isocyanate, isothiocyanate and alkylnitrile groups.
  • cycloalkyl refers to a saturated or partially unsaturated (eg cycloalkenyl) cyclic group which has one or more rings (preferably 1 or 2) which in particular have 3 to 14 ring carbon atoms, preferably 3 to 10 (in particular 3, 4, 5, 6 or 7) contains ring carbon atoms.
  • cycloalkyl groups are the cyclopropyl, cyclobutyl, cyclopentyl, spiro [4,5] decanyl, norbornyl, cyclohexyl, cyclopentenyl, cyclohexadienyl, decalinyl, cubanyl, bicyclo [4.3.0] nonyl , Tetralin, cyclopentylcyclohexyl, fluorocyclohexyl or the cyclohex-2-enyl group.
  • heterocycloalkyl refers to a cycloalkyl group as defined above in which one or more (preferably 1, 2 or 3) ring carbon atoms are included Oxygen, nitrogen, silicon, selenium, phosphorus or sulfur atom (preferably oxygen, sulfur or nitrogen) are replaced.
  • a heterocycloalkyl group preferably has 1 or 2 rings with 3 to 10 (in particular 3, 4, 5, 6 or 7) ring atoms.
  • Examples are the piperidyl, morpholinyl, urotropinyl, pyrrolidinyl, tetrahydrothiophenyl, tetrahydropyranyl, tetrahydrofuryl, oxacyclopropyl, azacyclopropyl or 2-pyrazolinyl group and also lactams, lactones, cyclic imides and cyclic anhydrides.
  • alkylcycloalkyl refers to groups containing, in accordance with the above definitions, both cycloalkyl and alkyl, alkenyl or alkynyl groups, e.g. Alkylcycloalkyl, alkylcycloalkenyl, alkenylcycloalkyl and alkynylcycloalkyl groups.
  • An alkylcycloalkyl group preferably contains a cycloalkyl group which has one or two rings with 3 to 10 (in particular 3, 4, 5, 6 or 7) ring carbon atoms and one or two alkyl, alkenyl or alkynyl groups having 1 or 2 to 6 carbon atoms contains.
  • heteroalkylcycloalkyl refers to alkylcycloalkyl groups as defined above in which one or more (preferably 1, 2 or 3) ring carbon atoms and / or carbon atoms are replaced by an oxygen,
  • a heteroalkylcycloalkyl group has 1 or 2 rings of 3 to 10 (especially 3, 4, 5, 6 or 7) ring atoms and one or two alkyl, alkenyl, alkynyl or heteroalkyl groups of 1 or 2 to 6 carbon atoms.
  • Examples of such groups are alkylheterocycloalkyl, alkylheterocycloalkenyl, alkenylheterocycloalkyl, alkynylheterocycloalkyl, heteroalkylcycloalkyl, heteroalkylheterocycloalkyl and heteroalkylheterocycloalkenyl wherein the cyclic groups are saturated or mono-, di- or triunsaturated.
  • aryl or Ar refers to an aromatic group which has one or more rings having in particular 6 to 14 ring carbon atoms, preferably 6 to 10 (in particular 6) ring carbon atoms.
  • aryl (or Ar) furthermore refers to groups in which one or more hydrogen atoms are represented by fluorine, chlorine, bromine or iodine atoms or -COOH, -OH, -SH, -NH 2 , or -NÜ 2 - Groups are replaced. Examples are the phenyl, naphthyl, biphenyl, 2-fluorophenyl, anilinyl, 3-nitrophenyl or 4-hydroxy-phenyl group.
  • heteroaryl refers to an aromatic group which contains one or more rings having in particular 5 to 14 ring atoms, preferably 5 to 10 (in particular 5 or 6) ring atoms, and one or more (preferably 1, 2, 3 or 4) oxygen atoms. , Nitrogen, phosphorus or sulfur ring atoms (preferably 0, S or N).
  • heteroaryl further refers to groups in which one or more hydrogen atoms are replaced by fluorine, chlorine, bromine or iodine atoms or -COOH, -OH, -SH, -NH 2 or -NO 2 groups.
  • Examples are 4-pyridyl, 2-imidazolyl, 3-phenylpyrrolyl, thiazolyl, oxazolyl, triazolyl, tetrazolyl, isoxazolyl, indazolyl, indolyl, Benzimidazolyl, pyridazinyl, quinolinyl, purinyl, carbazolyl, acridinyl, pyrimidyl, 2, 3 '-Bifuryl-, 3-pyrazolyl and isoquinolinyl groups.
  • aralkyl refers to groups containing, in accordance with the above definitions, both aryl and alkyl, alkenyl, alkynyl and / or cycloalkyl groups, e.g. Arylalkyl, alkylaryl, arylalkenyl, arylalkynyl, arylcycloalkyl, arylcycloalkenyl, alkylarylcycloalkyl and alkylarylcycloalkenyl groups.
  • aralkyls are toluene, xylene, mesitylene, styrene, benzyl chloride, o-fluorotoluene, 1H-indene, tetralin, dihydronaphthalene, indanone, phenylcyclopentyl, cumene, cyclohexylphenyl, fluorene and indane.
  • An aralkyl group preferably contains one or two aromatic rings having 6 to 10 ring carbon atoms and one or two alkyl, alkenyl and / or alkynyl groups having 1 or 2 to 6 carbon atoms and / or a cycloalkyl group having 5 or 6 ring carbon atoms.
  • heteroaralkyl refers to an aralkyl group as defined above in which one or more (preferably 1, 2, 3 or 4) ring carbon atoms and / or carbon atoms are represented by an oxygen, nitrogen, silicon, selenium, phosphorus, boron - or sulfur atom (preferably oxygen, sulfur or nitrogen) are replaced, ie groups which according to the above definitions both aryl or heteroaryl as well as alkyl, alkenyl, alkynyl and / or heteroalkyl and / or cycloalkyl and / or heterocycloalkyl groups.
  • a heteroaralkyl group contains one or two aromatic rings having 5 or 6 to 10 ring carbon atoms and one or two alkyl, alkenyl and / or alkynyl groups having 1 or 2 to 6 carbon atoms and / or a Cycloalkyl group having 5 or 6 ring carbon atoms, wherein 1, 2, 3 or 4 of these carbon atoms are replaced by oxygen, sulfur or nitrogen atoms.
  • Examples are arylheteroalkyl, arylheterocycloalkyl,
  • Ci-C ⁇ alkyl C 2 -C O alkenyl, C 2 -C 6 alkynyl, Ci-C ⁇ heteroalkyl, C 3 -C 0 cycloalkyl, C 2 -Cg heterocycloalkyl, C ⁇ -Cio aryl, C1-C9 heteroaryl, C 7 -C 2 aralkyl or C 2 -Cn heteroaralkyl groups are substituted.
  • Compounds of formula (I) may contain one or more chiral centers due to their substitution.
  • the present invention therefore encompasses both all pure enantiomers and all pure diastereomers, as well as their mixtures in any mixing ratio.
  • all cis / trans isomers of the compounds of the general formula (I) and mixtures thereof are also encompassed by the present invention.
  • all tautomeric forms of the compounds of the formula (I) are encompassed by the present invention.
  • X is a group of the formula -CH 2 -CO-NHOH, -CO-NHOH, -CH 2 -NOH-CHS, -NOH-CHS, -CH 2 -NOH-CHO, -NOH-CHO, -CH 2 -CO-CH 2 OH, -CO-CH 2 OH, -CH 2 -CHOH-CHO, -CHOH-CHO or a group having one of the following formulas:
  • X is preferably a group of the formula -CO-NHOH.
  • Ri is a hydrogen atom.
  • R 2 is a C 3 _ 7 alkyl or C 3 _ 7 alkyl or hetero-C 3-7 alkylcycloalkyl, or heteroalkyl cycloalkyl group; in particular an n-butyl or an n-pentyl group.
  • R 3 is a hydrogen atom or a methyl group, or R 3 and R 4 together form part of an optionally substituted cycloalkyl ring or Heterocycloalkylrings having preferably 3 to 8 ring atoms, in particular 4-6 ring atoms
  • R 4 is a hydrogen atom or an optionally substituted heteroaryl radical; in particular a hydrogen atom, a pyridyl, benzofuranyl, furanyl, thiazolyl, imidazolyl or a p-Aminobenzamidinylrest.
  • R 5 is an optionally substituted C 20 alkyl group, an optionally substituted branched C 20 alkyl group, an optionally substituted aryl, heteroaryl or an optionally substituted cycloalkyl group.
  • R 5 is an optionally substituted C 2 - 6 alkyl group or an optionally substituted branched C 2 - 6 alkyl group, an o-, m- or p-substituted or o- and m-disubstituted phenyl group.
  • R 5 is a propyl, isopropyl, phenyl, o-nitrophenyl, p-hydroxyphenyl, m-hydroxyphenyl, m, p-dihydroxyphenyl, m-amidinophenyl, cyclohexyl, cyclopropyl or 3 ' -Indolyl distr.
  • radicals Re and R 7 are hydrogen atoms.
  • n is equal to 1.
  • Examples of pharmacologically acceptable salts of the compounds of the formula (I) are salts of physiologically acceptable mineral acids such as hydrochloric acid, sulfuric acid and phosphoric acid; or salts of organic acids such as methanesulfonic acid, p-toluenesulfonic acid, lactic acid, formic acid, acetic acid, trifluoroacetic acid, citric acid, succinic acid, fumaric acid, maleic acid and salicylic acid.
  • Compounds of the formula (I) can be solvated, especially be hydrated. For example, hydration may occur during the manufacturing process or as a result of the hygroscopic nature of the initially anhydrous compounds of formula (I).
  • compositions according to the present invention contain at least one compound of formula (I) as active ingredient and optionally excipients and / or adjuvants.
  • the prodrugs (eg RB Silverman, Medicinal Chemistry, VCH Weinheim, 1995, Chapter 8, p. 361ff), which are also the subject of the present invention, consist of a compound of formula (I) and at least one pharmacologically acceptable protecting group is cleaved under physiological conditions, eg a hydroxy, alkoxy, aralkyloxy, acyl or acyloxy group, e.g. a methoxy, ethoxy, benzyloxy, acetyl or acetyloxy group.
  • physiological conditions eg a hydroxy, alkoxy, aralkyloxy, acyl or acyloxy group, e.g. a methoxy, ethoxy, benzyloxy, acetyl or acetyloxy group.
  • compounds of the formula (I) are of great interest, above all, as inhibitors of metalloproteinases (in particular of PDF).
  • the use of these active ingredients for the preparation of medicaments for the prevention and / or treatment of diseases, in particular those which are mediated by PDF, is the subject of the present invention.
  • compounds of formula (I) using the known and acceptable modes, either alone or in combination with any other therapeutic agent.
  • the administration can take place, for example, in one of the following ways: orally, eg as dragees, coated tablets,
  • the therapeutically useful product may be mixed with pharmacologically inert, inorganic or organic excipients, e.g.
  • excipients such as e.g. vegetable oils, petroleum, animal or synthetic oils, wax, grease, polyols. to
  • excipients such as water, alcohols, aqueous saline, aqueous dextrose, polyols, glycerol, vegetable oils, petroleum, animal or synthetic oils.
  • excipients such as vegetable oils, petroleum, animal or synthetic oils, wax, fat and polyols.
  • aerosol formulations one can use compressed gases that are suitable for this purpose, such as oxygen, nitrogen and carbon dioxide.
  • the pharmaceutically acceptable agents may also contain additives for preservation, stabilization, emulsifiers, sweeteners, flavorings, salts for Containing changes in osmotic pressure, buffers, coating additives and antioxidants.
  • the plate was shaken for 20 min at RT.

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Abstract

La présente invention concerne des composés de formule (I). Ces composés sont de nouveaux inhibiteurs de la peptide déformylase (PDF) et présentent un grand intérêt, en particulier, comme antibiotiques, agents anticancéreux, antiparasitaires et herbicides.
PCT/EP2006/005429 2005-06-07 2006-06-07 Inhibiteurs de la peptide deformylase (pdf) 3 WO2006131340A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102005026231A DE102005026231A1 (de) 2005-06-07 2005-06-07 Peptid-Deformylase (PDF) Inhibitoren 3
DE102005026231.7 2005-06-07

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WO2006131340A3 WO2006131340A3 (fr) 2007-04-19

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008127275A2 (fr) * 2006-09-22 2008-10-23 Ptc Therapeutics, Inc. Composés pyrrolidone en tant qu'inhibiteurs d'hydrolase d'arnt peptidyle bactérienne et utilisations de ceux-ci
US11034669B2 (en) 2018-11-30 2021-06-15 Nuvation Bio Inc. Pyrrole and pyrazole compounds and methods of use thereof

Citations (3)

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Publication number Priority date Publication date Assignee Title
WO2002102790A1 (fr) * 2001-06-15 2002-12-27 Vicuron Pharmaceuticals Inc. Composes de n-formyle hydroxylamine en tant qu'inhibiteurs de peptidyle deformylase (pdf)
WO2004099124A2 (fr) * 2003-05-08 2004-11-18 Morphochem Aktiengesellschaft für kombinatorische Chemie Nouveaux bioisosteres d'actinonine
WO2005027882A1 (fr) * 2003-09-22 2005-03-31 Bionetworks Gmbh Prevention et traitement de la perte osseuse induite par inflammation et/ou immuno-mediee

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