IL158056A - Chemical derivatives and pharmaceutical compositions containing them for use as anti-telomerase agent - Google Patents

Chemical derivatives and pharmaceutical compositions containing them for use as anti-telomerase agent

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IL158056A
IL158056A IL158056A IL15805603A IL158056A IL 158056 A IL158056 A IL 158056A IL 158056 A IL158056 A IL 158056A IL 15805603 A IL15805603 A IL 15805603A IL 158056 A IL158056 A IL 158056A
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radical
alkyl
optionally substituted
amino
group
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IL158056A
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Aventis Pharma Sa
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Priority claimed from FR0103916A external-priority patent/FR2822468B1/en
Application filed by Aventis Pharma Sa filed Critical Aventis Pharma Sa
Publication of IL158056A publication Critical patent/IL158056A/en

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    • 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
    • C07D401/14—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 three or more hetero rings
    • 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
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C07D401/12—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 chain containing hetero atoms as chain links
    • 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
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems

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  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Claims (32)

156 158056/2 C L A I M S
1. A compound which binds a G-quadruplex structure of DNA or =*/ RNA, wherein the compound corresponds to the following formula : nitrogen-containing aromatic ring—NR3—distribution agent— NR ' 3—aromatic ring in which: the nitrogen-containing aromatic ring represents: a quinolinyl or isoquinolinyl radical optionally substituted with at least one radical chosen from among: N (Ra ) (Rb) , wherein Ra and Rb are identical or different and represent hydrogen or C1-C4 alkyl radical, and a short-chain C1-C4 alkoxy or alkyl group, a quinolinyl or isoquinolinyl radical possessing a nitrogen atom in quaternary form, or a pyridinyl radical; or wherein the nitrogen-containing ring is replaced by a benzimidinyl radical; the aromatic ring represents: a quinolinyl radical optionally substituted with at least one radical chosen from among: N (Ra) (Rb) , wherein Ra and Rb are identical or different and represent hydrogen or C1-C4 alkyl radical, and a short-chain C1-C4 alkoxy or alkyl group, a quinolinyl radical possessing a nitrogen atom in quaternary form, benzamidinyl radical, a pyridinyl radical, a phenyl ring optionally substituted with a halogen chosen from iodine, bromine or fluorine, C1-C4 alkoxy group, cyano group, carbonylamino group optionally substituted with one or more C1-C4 alkyl groups, guanyl 157 158056/2 group, C1-C4 alkylthio group, amino group, C1-C4 alkylamino group, C1-C4 dialkylamino group for each alkyl, C1-C4 dialkylamino group for each alkyl in which the alkyl portions together form a C3-C8 ring, nitro group, C1-C4 alkyleneamino group, or C2-C4 alkenyleneamino group, or a mono- or bi- or tricyclic heterocyclic ring comprising 0 to 2 heteroatoms per ring wherein at least one heteroatom is present in at least one ring that is optionally substituted with one or more C1-C4 alkyl groups, C1-C4 alkylene groups, or C2-C4 alkenylene groups; R3 and R'3 are identical or different and represent, independently of one another, hydrogen or C1-C4 alkyl radical; the distribution agent represents: a triazine group, wherein the triazine group is a [1, 3, 5] triazine optionally substituted with: an aromatic ring as defined above, or a radical XR1(R2), where X represents a nitrogen to form NR1R2, a linear or branched C1-C6 alkyl radical to form alkRlR2, an oxygen to form OR1, or a sulfur to form SRI, wherein Rl and R2, which are identical or different, are chosen from among hydrogen; a C1-C8 alkyl radical optionally' substituted with one or more radicals which are identical or different; an aromatic ring as defined above; a quinuclidine radical; a pyrrolidinyl radical which is optionally substituted with an alkyl or phenylalkyl radical where alkyl is C1-C4 alkyl; a piperazinyl radical which is optionally substituted with an alkyl, cycloalkyl or phenylalkyl radical; a morpholinyl radical; a pyridyl radical or a piperidyl radical which are optionally substituted with one or more alkyl or phenylalkyl radicals where alkyl is C1-C4 alkyl; an indazolyl radical; a naphthyl radical; a benzotriazole 158 158056/2 radical; a pyrimidinyl radical optionally substituted with one or more C1-C4 alkyls; and an acenaphthene radical; or a radical where X represents N or alkyl, Rl and R2 are as defined above, and Rl, R2 and X form a saturated or unsaturated 3- to 6-membered monocyclic or 8- to 10- membered bicyclic radical optionally containing one or two identical or different heteroatoms chosen from N, 0 or S; with the provisos that if X represents a nitrogen and Rl and R2 are identical, then Rl and R2 do not both represent hydrogen or unsubstituted C1-C4 alkyl, and if X represents a nitrogen and Rl and R2 are different, then one does not represent hydrogen and the other an unsubstituted C1-C4 alkyl; or any salts, isomeric forms, racemates, enantiomers and diastereoisomers thereof.
2. The compound of claim 1, wherein one or both of Rl and R2 represents a C1-C8 alkyl radical optionally substituted with one or more radicals which are identical or different, chosen from among: an amino radical which is optionally substituted with one or two radicals which are identical or different, chosen from alkyl, hydroxyalkyl, alkoxyalkyl, phenylalkyl, carboxyalkyl, hydroxycarboxyalkyl, acyl, naphthyl, phenyl and alkylphenyl radicals; a trialkylammonium radical; a hydroxyl radical; a C1-C4 alkoxy radical; a thioalkoxy radical; a trifluoromethyl radical; a free, salified, esterified or amidated carboxyl radical; a pyrrolidinyl radical optionally substituted with C1-C4 alkyl; 159 158056/2 a piperidyl radical; a piperazinyl radical optionally substituted with alkyl or phenylalkyl where alkyl is C1-C4 alkyl; a morpholinyl radical; a pyridyl radical; and a naphthyl radical or phenyl radical optionally substituted with one or more radicals chosen from C1-C4 alkoxy radicals, halogen or an amino radical optionally substituted as defined above.
3. The compound of claim 1, wherein the distribution agent represents a triazine group optionally substituted with: an aromatic ring as defined in claim 1, or a radical XR1(R2), where X represents a nitrogen to form NR1R2, a linear or branched C1-C6 alkyl radical to form alkRlR2, an oxygen to form OR1, or a sulfur to form SRI, wherein Rl and R2, which are identical or different, are chosen from: hydrogen; a C1-C8 alkyl radical optionally substituted with one or more radicals chosen from the radicals amino, alkylamino, dialkylamino, dialkoxyalkylamino, dihydroxyalkylamino, alkoxyalkylamino, hydroxyalkylamino, hydroxycarboxy- alkylamino, trialkylamino, naphthylamino, phenylamino, acylamino, (alkyl) (phenylalkyl ) amino, phenyl) (alkyl) amino, (alkylphenyl) (alkyl) amino, hydroxyl, C1-C4 alkoxy, C1-C4 thioalkoxy, trifluoromethyl, free, salified, esterified or amidated carboxyl, pyrrolidinyl optionally substituted with C1-C4 alkyl, piperidyl, piperazinyl optionally substituted with alkyl or phenylalkyl with alkyl as C1-C4, morpholinyl, pyridyl, naphthyl or phenyl optionally substituted with one or more radicals chosen from the radicals C1-C4 alkoxy, halogen, amino, alkylamino and dialkylamino; an aromatic ring as defined in claim 1; 160 158056/3 a quinuclidine radical; a pyrrolidinyl radical which is optionally substituted with an alkyl or phenylalkyl radical where alkyl is C1-C4 alkyl ; a piperazinyl radical which is optionally substituted with an alkyl, cycloalkyl or phenylalkyl radical; a morpholinyl radical; a pyridyl radical or a piperidyl radical which are optionally substituted with one or more alkyl or phenylalkyl radicals with alkyl is C1-C4 alkyl; an indazolyl radical; a naphthyl radical; a benzotriazole radical; a pyrimidinyl radical optionally substituted with one or more C1-C4 alkyls; and an acenaphthene radical; or a radical where X represents N or alkyl, Rl and R2 are as defined above, and Rl, R2 and X form a radical chosen from the following radicals: piperazinyl optionally substituted with one or more radicals which are identical or different; pyrrolidinyl optionally substituted with C1-C4 alkyl or alkoxy, hydroxyl, acylamino, pyrrolidinylalkyl and pyridyl; 1,2,3,4-tetrahydroisoquinolinyl; diazepine optionally substituted with alkyl or pyrrolidinylalkyl; piperidyl optionally substituted with alkyl, alkoxy or alkoxyalkyl, hydroxyl and cycloalkylalkyl; morpholinyl; imidazolinyl optionally substituted with alkyl, with the provisos that if X represents a nitrogen and Rl and R2 are identical, then Rl and R2 do not both represent hydrogen or unsubstituted C1-C4 alkyl, and if X represents a nitrogen and Rl and R2 are different, then one does not represent hydrogen and the other an unsubstituted C1-C4 alkyl; or a diazine group, 161 158056/2 wherein the diazine group is optionally substituted with any of the groups defined above for the triazine group; or any salts, isomeric forms, racemates, enantiomers and diastereoisomers thereof.
4. The compound of claim 1, wherein X in XR1(R2) is nitrogen, and one of Rl and R2 is as defined in claim 1 and the other of Rl and R2 represents hydrogen or C1-C4 alkyl radical optionally substituted with an amino, alkylamino, dialkylamino or phenyl radical; or Rl, R2, and the nitrogen atom to which they are attached, form a piperazinyl radical optionally substituted with one or more radicals chosen from alkyl; aminoalkyl; alkylaminoalkyl; dialkylaminoalkyl ; phenylalkyl; alkoxyalkyl; hydroxyalkyl; hydroxyalkoxyalkyl; alkoxy; pyrrolidinylalkyl; C3-C8 cycloalkyl; pyrazinyl; pyrimidinyl; pyridyl; furylcarbonyl ; furfurylcarbonyl ; quinolyl; pyrrolidinyl optionally substituted with C1-C4 alkyl, C1-C4 alkoxy, hydroxyl, acylamino, pyrrolidinylalkyl, or pyridyl; 1,2,3,4- tetrahydroisoquinolinyl; diazepine optionally substituted with alkyl or pyrrolidinylalkyl; piperidyl optionally substituted with alkyl, alkoxy or alkoxyalkyl; hydroxyl; cycloalkylalkyl; morpholinyl; and imidazolinyl optionally substituted with alkyl.
5. The compound of claim 1, wherein the compound corresponds to the following formula: nitrogen-containing aromatic ring—NR3—distribution agent— NR ' 3—aromatic ring in which the nitrogen-containing aromatic ring represents: a quinolinyl or isoquinolinyl radical optionally substituted with at least one radical chosen from among: 162 158056/2 N(Ra) (Rb), wherein Ra and Rb are identical or different and represent hydrogen or C1-C4 alkyl radical, and a short-chain C1-C4 alkoxy or alkyl group, a quinolinyl radical possessing a nitrogen atom in quaternary form, or a pyridinyl radical; or wherein the nitrogen-containing ring is replaced by a benzimidinyl radical; the aromatic ring represents: a quinolinyl radical optionally substituted with at least one radical chosen from among: N (Ra) (Rb) , wherein Ra and Rb are identical or different and represent hydrogen or C1-C4 alkyl radical, and a short-chain C1-C4 alkoxy or alkyl group, a quinolinyl radical possessing a nitrogen atom in quaternary form, a benzamidinyl radical, a pyridinyl radical, a phenyl ring optionally substituted with a halogen chosen from iodine, bromine or fluorine, C1-C4 alkoxy group, cyano group, carbonylamino group optionally substituted with one or more C1-C4 alkyl groups, guanyl group, C1-C4 alkylthio group, amino group, C1-C4 alkylamino group, C1-C4 dialkylamino group, C1-C4 dialkylamino group in which the alkyl portions together form a C3-C8 ring, nitro group, C1-C4 alkyleneamino group, or C2-C4 alkenyleneamino group, or a mono- or bi- or tricyclic heterocyclic ring comprising 0 to 2 heteroatoms per ring wherein at least one heteroatom is present in at least one ring that is optionally substituted with one or more C1-C4 alkyl groups, C1-C4 alkylene, or C2-C4 alkenylene groups; R3 and R'3 are identical or different and represent, independently of one another, hydrogen or C1-C4 alkyl radical; the distribution agent represents: 163 158056/2 a triazine group, wherein the triazine group is a [1, 3, 5] triazine optionally substituted with: a radical XR1(R2), where X represents a nitrogen to form NR1R2 , a linear or branched C1-C6 alkyl radical to form alkRlR2, an oxygen to form OR1, or a sulfur to form SRI, wherein Rl and R2, which are identical or different, are chosen from among hydrogen; C1-C8 alkyl optionally substituted with a radical chosen from amino, alkylamino, dialkylamino, (phenyl ) (alkyl ) amino, (alkylphenyl) (alkyl) - amino, C1-C4 alkoxy, C1-C4 thioalkoxy, trifluoromethyl, pyrrolidiny, piperidyl, piperazinyl, morpholinyl, pyridyl and phenyl; an aromatic ring as defined in claim 1, a quinuclidine radical; a pyrrolidinyl, piperazinyl, morpholinyl, pyridyl or a piperidyl radical optionally substituted with C1-C4 alkyl; or a radical where X represents N or alkyl, Rl and R2 are as defined above, and Rl, R2 and X form a saturated or unsaturated 3- to 6-membered monocyclic or 8- to 10- membered bicyclic radical optionally containing one or two identical or different heteroatoms chosen from N, 0 or S; with the provisos that if X represents a nitrogen and Rl and R2 are identical, then Rl and R2 do not both represent hydrogen or unsubstituted C1-C4 alkyl, and if X represents a nitrogen and Rl and R2 are different, then one does not represent hydrogen and the other an unsubstituted C1-C4 alkyl; or any salts, isomeric forms, racemates, enantiomers and diastereoisomers thereof.
6. The compound of claim 1, wherein the distribution agent represents : 164 158056/2 a [1, 3, 5] triazine optionally substituted with a radical XR1(R2) where X represents a nitrogen to form NR1R2, an oxygen to form OR1, or a sulfur to form SRI, wherein R2 and R2, which are identical or different, are chosen from among: hydrogen, C1-C8 alkyl optionally substituted with a radical chosen from amino, alkylamino, dialkylamino, (phenyl) (alkyl) amino, (alkylphenyl ) (alkyl ) -amino, C1-C4 alkoxy, pyrrolidinyl, pyridyl, and phenyl, an aromatic ring as defined in claim 1; a quinuclidine radical; a pyrrolidinyl radical; and a piperidyl radical optionally substituted with C1-C4 alkyl, or radical where X represents N, Rl and R2 are as defined above, and Rl, R2, and X form a piperazinyl, piperidyl, pyrrolidinyl, morpholinyl or thiomorpholinyl radical, with the provisos that if X represents a nitrogen and Rl and R2 are identical, then Rl and R2 do not both represent hydrogen or unsubstituted C1-C4 alkyl, and if X represents a nitrogen and Rl and R2 are different, then one does not represent hydrogen and the other an unsubstituted C1-C4 alkyl-; or any salts, isomeric forms, racemates, enantiomers and diastereoisomers thereof.
7. The compound of claim 1, corresponding to formula (I) below: 165 158056/2 wherein: A represents a radical XR1(R2) in which X represents a nitrogen, oxygen, or sulfur atom or a C1-C6 alkyl radical in order to form one of the following radicals: NR1R2, wherein Rl and R2 are identical or different and are chosen from: hydrogen; C1-C8 alkyl optionally substituted with one or more radicals which are identical or different; an aromatic ring as defined in claim 1; a quinuclidine radical; a pyrrolidinyl radical which is itself optionally substituted with alkyl or phenylalkyl radical with alkyl as C1-C4; a piperazinyl radical which is itself optionally substituted with an alkyl, cycloalkyl or phenylalkyl radical; a morpholinyl radical; a pyridyl radical or a piperidyl radical which is optionally substituted with one or more alkyl or phenylalkyl radicals with C1-C4 alkyl; an indazolyl radical; a naphthyl radical; a benzotriazole radical; a pyrimidinyl radical optionally substituted with one or more alkyls with alkyl as C1-C4; and an acenaphthene radical; or a radical where X represents N or alkyl, Rl and R2 are as defined above, and Rl, R2 and X form a saturated or unsaturated 3- to 6-membered monocyclic or 8- to 10-membered bicyclic radical optionally containing one or 166 158056/2 two identical or different heteroatoms chosen from N, 0 or S; with the provisos that if X represents a nitrogen and Rl and R2 are identical, then Rl and R2 do not both represent hydrogen or unsubstituted C1-C4 alkyl, and if X represents a nitrogen and Rl and R2 are different, then one does not represent hydrogen and the other an unsubstituted C1-C4 alkyl; a group OR1 or SRI, wherein Rl has the same meaning as above, with the proviso that Rl does not represent hydrogen or unsubstituted C1-C4 alkyl, or an alkyl group containing from 1 to 6 carbon atoms, substituted with Rl and R2 as defined above; R3 and R'3, which are identical or different, represent independently of one another hydrogen or a C1-C4 alkyl group; Ari and Ar2, if identical, represent: a quinolinyl radical optionally substituted with at least one group N(Ra) (Rb) in which Ra and Rb, which are identical or different, represent hydrogen, a C1-C4 alkyl radical, or a short-chain alkoxy or alkyl group containing 1 to 4 carbon atoms, or a quinolinyl radical possessing a nitrogen atom in quaternary form or a benzamidinyl radical, or a pyridinyl radical attached at the 4-position or fused with an aryl or heteroaryl group optionally substituted with a C1-C4 alkyl group; and Ari and Ar2, when different: both represent one of the radicals recited above for Ari and Ar2, or Ari represents one of the above radicals and Ar2 represents a phenyl ring optionally substituted with a halogen chosen from iodine, bromine or fluorine, C1-C4 alkoxy group, cyano group, carbonylamino group optionally substituted with one or more C1-C4 alkyl groups, guanyl group, C1-C4 alkylthio group, amino group, C1-C4 167 158056/2 alkylamino group, C1-C4 dialkylamino group, nitro group, C1-C4 alkyleneamino group, or C2-C4 alkenyleneamino group, or a piperazinyl radical optionally substituted with a C1-C4 alkyl radical, or a mono-, bi-, or tricyclic heterocyclic ring comprising 0 to 2 heteroatoms per ring provided that at least one heteroatom is present in at least one ring that is optionally substituted with one or more C1-C4 alkyl groups, C1-C4 alkylene, or C2-C4 alkenylene groups; or any salts, isomeric forms, racemates, enantiomers and diastereoisomers thereof.
8. The compound of claim 7, wherein one or both of Rl and R2 represents a C1-C8 alkyl radical optionally substituted with one or more radicals which are identical or different, wherein these radicals are chosen from an amino radical optionally substituted with one or two radicals which are identical or different, chosen from alkyl, hydroxyalkyl, alkoxyalkyl, phenylalkyl, carboxyalkyl, hydroxycarboxyalkyl, acyl, naphthyl, phenyl and alkylphenyl radicals; trialkylammonium radical; hydroxyl radical; alkoxy radical; thioalkoxy radical; trifluoromethyl radical; free, salified, esterified or amidated carboxyl radical; pyrrolidinyl radical optionally substituted with C1-C4 alkyl; piperidyl radical; piperazinyl radical optionally substituted with alkyl or phenylalkyl where alkyl is C1-C4 alkyl; morpholinyl radical; pyridyl radical; and naphthyl radical or phenyl radical optionally substituted with one or more radicals chosen from C1-C4 alkoxy radicals, halogen or amino radical optionally substituted as defined above.
9. The compound of claim 1, wherein X in XR1(R2) represents N, one of Rl and R2 represents a hydrogen atom and the 168 158056/2 other of Rl and R2 is as defined in claim 1; or Rl and R2, together with the nitrogen atom to which they are attached, form a piperazinyl, pyrrolidinyl, piperidyl, morpholinyl, thiomorpholinyl, imidazolinyl, diazepine, or 1, 2, 3, 4-tetrahydroisoquinoline radical, all these radicals being optionally substituted with one or more radicals .
10. The compound of claim 7, wherein A represents an aromatic ring as defined above or a radical XR1(R2) in which X represents' a nitrogen to form NR1R2, a linear or branched C1-C6 alkyl radical to form alkRlR2, an oxygen to form OR1, or a sulfur to form SRI, wherein Rl and R2, which are identical or different, are chosen from: hydrogen; C1-C8 alkyl optionally substituted with one or more radicals chosen from amino, alkylamino, dialkylamino, dialkoxyalkylamino, dihydroxyalkylamino, alkoxyalkylamino, hydroxyalkylamino, hydroxycarboxyalkylamino, trialkylammonium, naphthylamino, phenylamino, acylamino, (alkyl) (phenylalkyl) amino, (phenyl) (alkyl ) amino, (alkylphenyl) (alkyl) amino, hydroxyl, C1-C4 alkoxy, C1-C4 thioalkoxy, trifluoromethyl , free, salified, esterified or amidated carboxyl, pyrrolidinyl optionally substituted with C1-C4 alkyl, piperidyl, piperazinyl optionally substituted with alkyl or phenylalkyl with alkyl as Cl- C4, morpholinyl, pyridyl, naphthyl or phenyl optionally substituted with one or more radicals chosen from the radicals C1-C4 alkoxy, halogen, amino, alkylamino and dialkylamino; an aromatic ring as defined in claim 7; quinuclidine radical; 169 158056/2 a pyrrolidinyl radical which is itself optionally substituted with an alkyl or phenylalkyl radical with alkyl as C1-C4; a piperazinyl radical which is itself optionally substituted with an alkyl, cycloalkyl or phenylalkyl radical; a morpholinyl radical; a pyridyl radical or a piperidyl radical which are optionally substituted with one or more alkyl or phenylalkyl radicals with C1-C4 alkyl; an indazolyl radical; a naphthyl radical, a benzotriazole radical; a pyrimidinyl radical optionally substituted with one or more C1-C4 alkyl radicals; and an acenaphthene radical; or Rl and R2, together with the X to which they are attached, form a radical chosen from the following radicals: piperazinyl optionally substituted with one or more radicals which are identical or different; pyrrolidinyl optionally substituted with C1-C4 alkyl or alkoxy, hydroxyl, acylamino, pyrrolidinylalkyl and pyridyl; 1, 2, 3, 4-tetrahydroisoquinolinyl; diazepine optionally substituted with alkyl or pyrrolidinylalkyl; piperidyl optionally substituted with alkyl, alkoxy or alkoxyalkyl, hydroxyl and cycloalkylalkyl; morpholinyl; and imidazolinyl optionally substituted with alkyl; with the provisos that if X represents a nitrogen and Rl and R2 are identical, then Rl and R2 do not both represent hydrogen or unsubstituted C1-C4 alkyl, and if X represents a nitrogen and Rl and R2 are different, then one does not represent hydrogen and the other an unsubstituted C1-C4 alkyl. 170 158056/2
11. The compound of claim 7, wherein X in XR1(R2) represents N, and one of Rl and R2 represents a hydrogen or C1-C4 alkyl radical optionally substituted with an amino, alkylamino, dialkylamino or phenyl radical, and the other of Rl and R2 is as defined in claim 7; or Rl, R2, and the nitrogen atom to which they are attached, form a piperazinyl radical optionally substituted with one or more radicals chosen from alkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl , phenylalkyl, alkoxyalkyl, hydroxyalkyl, hydroxyalkoxyalkyl , alkoxy, pyrrolidinylalkyl, C3-C8 cycloalkyl, pyrazinyl, pyrimidinyl, pyridyl, furylcarbonyl, furfurylcarbonyl, quinolyl, pyrrolidinyl optionally substituted with C1-C4 alkyl or alkoxy, hydroxyl, acylamino, pyrrolidinylalkyl, pyridyl, 1, 2, 3, 4-tetrahydroiso-quinolinyl, diazepine optionally substituted with alkyl or pyrrolidinylalkyl, piperidyl optionally substituted with alkyl, alkoxy or alkoxyalkyl; hydroxyl; cycloalkylalkyl ; morpholinyl; and imidazolinyl optionally substituted with alkyl.
12. The compound of claim 7, wherein the compounds correspond to formula (I) below: wherein : A represents a radical XR1(R2) in which X represents a nitrogen, oxygen or sulfur atom, or a C1-C6 alkyl radical, to form one of the following radicals: NR1R2, wherein Rl and R2, which are identical or 171 158056/2 different, are chosen from a hydrogen atom; C1-C8 alkyl optionally substituted with an amino, alkylamino, dialkylamino, (phenyl) (alkyl) amino, (alkylphenyl) (alkyl) amino, C1-C4 alkoxy, C1-C4 thioalkoxy, trifluoromethyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, pyridyl or phenyl; an aromatic ring as defined in claim 7; a quinuclidine radical; and a pyrrolidinyl, piperazinyl, morpholinyl, pyridyl, ' or piperidyl radical optionally substituted with C1-C4 alkyl; or when X is N or alkyl, Rl and R2, together with the X to which they are attached, form a saturated or unsaturated 3- to 6-membered monocyclic or 8- to 10-membered bicyclic radical optionally containing one or two heteroatoms, which are identical or different, chosen from N, 0 or S, with the provisos that if X represents a nitrogen and Rl and R2 are identical, then Rl and R2 do not both represent hydrogen or unsubstituted C1-C4 alkyl, and if X represents a nitrogen and Rl and R2 are different, then one does not represent hydrogen and the other an unsubstituted C1-C4 alkyl; a group OR1 or SRI in which Rl has the same meaning as above, with the proviso that Rl does not represent hydrogen or unsubstituted C1-C4 alkyl; or an alkyl group containing from 1 to 6 carbon atoms, substituted with Rl and R2 as defined above; R3 and R'3, which are identical or different, represent independently of one another hydrogen or a C1-C4 alkyl group; Ari and Ar2, when identical, represent a quinolinyl radical optionally substituted with at least one group N(Ra) (Rb) in which Ra and Rb, which are identical or different, represent hydrogen, a C1-C4 alkyl radical, or a short-chain alkoxy or alkyl group containing 1 to 4 carbon atoms, 172 158056/2 a quinolinyl radical possessing a nitrogen atom in quaternary form, a benzamidinyl radical, or a pyridinyl radical attached at the 4-position or fused with an aryl or heteroaryl group optionally substituted with a C1-C4 alkyl group; and Ari and Ar2, when different: both represent one of the radicals recited above for Ari and Ar∑, or Ari represents one of the above recited radicals and Ar2 represents a phenyl ring optionally substituted- with a halogen chosen from iodine, bromine or fluorine, C1-C4 alkoxy group, cyano group, carbonylamino group optionally substituted with one or more C1-C4 alkyl groups, guanyl group, C1-C4 alkylthio group, amino group, C1-C4 alkylamino group, C1-C4 dialkylamino group for each alkyl group, nitro group, C1-C4 alkyleneamino group, C2-C4 alkenyleneamino group, or a piperazinyl radical optionally substituted with a C1-C4 alkyl radical, a mono- or bi- or tricyclic heterocyclic ring comprising 0 to 2 heteroatoms per ring provided that at least one heteroatom is present in at least one ring that is optionally substituted with one or more C1-C4 alkyl groups, C1-C4 alkylene, or C2-C4 alkenylene groups; or any salts, isomeric forms, racemates, enantiomers and diastereoisomers thereof.
13. The compound of claim 7, wherein the compound corresponds to formula (I) below: 173 158056/2 wherein: A represents a radical XR1(R2) in which X represents a nitrogen, oxygen or sulfur atom, or a C1-C6 alkyl radical, to form one of the following radicals: NR1R2, wherein Rl and R2, which are identical or different, are chosen from hydrogen; C1-C8 alkyl optionally substituted with a radical amino, alkylamino, dialkylamino, (phenyl) (alkyl ) amino, (alkylphenyl) (alkyl) amino, C1-C4 alkoxy, C1-C4 thioalkoxy, trifluoromethyl, pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, pyridyl or phenyl; an aromatic ring as defined in claim 7; a quinuclidine radical; and a pyrrolidinyl, piperazinyl, morpholinyl, pyridyl or piperidyl radical optionally substituted with C1-C4 alkyl; or Rl and R2, together with the X to which they are attached, form a saturated or unsaturated 3- to 6 membered monocyclic or 8- to 10-membered bicyclic radical optionally containing one or two heteroatoms., which are identical or different, chosen from N, 0 or S; with the provisos that if X represents a nitrogen and Rl and R2 are identical, then Rl and R2 do not both represent hydrogen or unsubstituted C1-C4 alkyl, and 174 158056/2 if X represents a nitrogen and Rl and R2 are different, then one does not represent hydrogen and the other an unsubstituted C1-C4 alkyl; a group ORl or SRI in which Rl has the same meaning as above, with the proviso that Rl does not represent hydrogen or unsubstituted C1-C4 alkyl; or an alkyl group containing from 1 to 6 carbon atoms, substituted with Rl and R2 as defined above; R3 and R'3, which are identical or different, represent independently of one another hydrogen or a C1-C4 alkyl group; Ari and Ar2, when identical, represent a quinolinyl radical optionally substituted with at least one group (Ra) (Rb) in which Ra and Rb, which are identical or different, represent hydrogen, a C1-C4 alkyl radical, or a short-chain alkoxy or alkyl group containing 1 to 4 carbon atoms, a quinolinyl radical possessing a nitrogen atom in quaternary form, a benzamidinyl radical, or a pyridinyl radical attached at the 4-position or fused with an aryl or heteroaryl group optionally substituted with a C1-C4 alkyl group; and Ari and Ar2, when different: both represent one of the radicals recited above for Ari and Ar2, or Ari represents one of the above recited radicals and Ar2 represents a phenyl ring optionally substituted with a halogen chosen from iodine, bromine or fluorine, C1-C4 alkoxy group, cyano group, carbonylamino group optionally substituted with one or more C1-C4 alkyl groups, guanyl group, C1-C4 alkylthio group, amino group, C1-C4 alkylamino group, C1-C4 dialkylamino group for each alkyl group, nitro group, C1-C4 alkyleneamino group, C2-C4 175 158056/2 alkenyleneamino group, or a piperazinyl radical optionally substituted with a C1-C4 alkyl radical, a mono- or bi- or tricyclic heterocyclic ring comprising 0 to 2 heteroatoms per ring provided that at least one heteroatom is present in at least one ring that is optionally substituted with one or more C1-C4 alkyl groups, C1-C4 alkylene, or C2-C4 alkenylene groups; or any salts, isomeric forms, racemates, enantiomers and diastereoisomers thereof.
14. The compound of claim 7, wherein A represents a radical XR1(R2) in which X represents nitrogen to form NR1R2, an oxygen to form OR1, or a sulfur to form SRI, to form one of the following radicals : NR1R2, wherein Rl and R2, which are identical or different, are chosen from hydrogen; C1-C8 alkyl optionally substituted with a amino, alkylamino, dialkylamino, (phenyl) (alkyl) amino, (alkylphenyl) (alkyl) amino, C1-C4 alkoxy, pyrrolidinyl, pyridyl or phenyl radical; an aromatic ring as defined in claim 7; a quinuclidine radical, a pyrrolidinyl radical or a piperidyl radical optionally substituted with C1-C4 alkyl; or Rl and R2, together with the X to which they are attached, form a piperazinyl, piperidyl, pyrrolidinyl, morpholinyl, or thiomorpholinyl radical, with the provisos that if X represents a nitrogen and Rl and R2 are identical, then Rl and R2 do not both represent hydrogen or unsubstituted C1-C4 alkyl, and if X represents a nitrogen and Rl and R2 are different, then one does not represent hydrogen and the other an unsubstituted C1-C4 alkyl; a group OR1 or SRI in which Rl has the same meaning as above, with the proviso that Rl does not represent hydrogen or unsubstituted C1-C4 alkyl; 176 158056/2 or any salts, isomeric forms, racemates, enantiomers and diastereoisomers thereof.
15. The compound of claim 7, wherein A represents NR1R2, and one of Rl and R2 represents hydrogen and the other of Rl and R2 is as defined in claim 7, or Rl and R2, together with the nitrogen atom to which they are attached, form a piperazinyl, pyrrolidinyl, piperidyl or morpholinyl radical .
16. The compound of claim 7, wherein Ari and Ar2 represent a group chosen from: 4-amino-, 4-methylamino-, 4- dimethylamino-quinolyl or -quinolinium in which the quinolinium ring is optionally substituted with a methyl group; or a phenyl optionally substituted with one or more halogen atoms chosen from iodine, bromine or fluorine .
17. The compound of claim 7, wherein A represents: an amino radical substituted with a radical chosen from the following groups: 4-amino-, 4-methylamino-, or 4- dimethylamino-quinolyl or -quinolinium in which the quinolinium ring is optionally substituted with a methyl; pyridyl; phenyl optionally substituted with one or more halogen atoms; piperazinyl or alkylpiperazinyl ; C1-C4 alkyl substituted with an amino, alkylamino or dialkylamino; (phenyl) (alkyl ) amino; (alkylphenyl) (alkyl) amino, C2-C4 alkoxy, with a pyrrolidinyl radical or with a phenyl radical, in which radicals the alkyl groups possess 1 to 4 carbon atoms; a pyrrolidinyl radical; a piperidyl radical optionally substituted with a C1-C4 alkyl radical; or a quinuclidine radical or a pyrrolidinyl radical, a morpholino radical or a piperazinyl radical optionally substituted with a C1-C4 alkyl radical or a radical 0- 177 158056/2 phenyl, O-pyridyl or O-alkyl substituted with an amino, alkylamino or dialkylamino radical.
18. The compound of claim 7, wherein Ari and Ar2 are identical, and Ari and Ar2 represent a group chosen from 4-amino-, 4-methylamino-, or 4-dimethylamino-quinolyl or -quinolinium in which the quinolinium ring is optionally substituted with a methyl group.
19. The compound of claim 7, wherein Ari and Ar2 are V different, and Ari represents : quinolinyl radical substituted with at least one group N(Ra) (Rb) in which Ra and Rb, which are identical or different, represent hydrogen or a C1-C4 alkyl radical or a short-chain alkoxy or alkyl group containing 1 to 4 carbon atoms, a quinolinyl radical possessing a nitrogen atom in quaternary form a benzamidinyl radical, except if A represents diethylamine, hydrogen, or an amine group, then Ari is not benzamidine, or a pyridinyl radical attached at the 4-position or fused with an aryl or heteroaryl group; and Ar2 represents : a ring as defined above, or a phenyl ring optionally substituted with a halogen chosen from iodine, bromine or fluorine, methoxy, cyano, carbonylamino, guanyl, methylthio, amino, methylamino, dimethylamino, morpholine, C1-C4 alkyleneamino or C2-C4 alkenyleneamino group, or a quinoline, benzimidazole, indole, benzothiophene, benzofuran, benzothiazole, benzoxazole, carbazole, quinazoline or quinoxaline ring optionally substituted with one or more C1-C4 alkyl groups, C1-C4 alkylene, or C2-C4 alkenylene groups. 178 158056/2
20. The compound of claim 7, wherein A represents an amino radical substituted with a radical chosen from among: 4- amino-, 4-methylamino-, or 4-dimethylamino-quinolinyl or -quinolinium radicals wherein the quinolinium ring is optionally substituted with a methyl group; C1-C4 alkyl radical substituted with an amino, alkylamino, dialkylamino, (phenyl) (alkyl) amino, (alkylphenyl) (alkyl) amino, pyrrolidinyl or pyridyl radical; or the quinuclidine radical. l
21. The compound of claim 7, wherein A represents either an amino radical substituted with a pyridyl radical; a phenyl radical optionally substituted with a piperazinyl or alkylpiperazinyl radical; a piperidyl radical optionally substituted with a C1-C4 alkyl radical; or a piperazinyl radical optionally substituted with a C1-C4 alkyl radical.
22. The compound of claim 7, wherein A represents O-phenyl, O-pyridyl, or O-alkyl substituted with an amino, alkylamino or dialkylamino radical.
23. The compound of claim 7, wherein A represents a radical O(or S) -aromatic ring or a radical 0(or S) -alkyl with alkyl optionally substituted.
24. The compound of claim 1, wherein the compound is: 2, 4-bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- (3-dimethylaminopropyl) amino- [1,3, 5] triazine, 2,4, 6-tris ( 4 -amino-2-methylquinolin-6-yl ) amino- [1,3,5] triazine, 2, -bis (4-amino-2-methylquinolin-6-yl) amino-6- (4- dimethylamino-2-methylquinolin-6-yl) amino- [1,3,5] triazine, 179 158056/2 2, -bis (4-amino-2-methylquinolin-6-yl) amino-6- (quinuclidin-3-yl) amino- [1,3,5] -triazine, 2, 4-bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- (1- methylpiperidin-4-yl ) -[1,3,5] triazine, 2, 4-bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- (1- methylpiperazin-4-yl) -[1,3,5] triazine, 2, 4-bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- (pyridin-4-yl) methylamino- [1,3,5] triazine, 2, 4-bis (4-amino-2-methylquinolin-6-yl) amino-6-phenoxy- [1,3,5] triazine, 2, 4-bis (4-amino-2-methylquinolin-6-yl) amino-6- (3- dimethylaminopropyl ) oxy- [1,3,5] triazine, 2, 4-bis (4-amino-2-methylquinolin-6-yl) amino-6- (pyridin-4- yl) oxy- [1, 3, 5] triazine, or 2, 4-bis (4-amino-2-methylquinolin-6-yl) amino-6- (phenylmethyl) oxy- [1,3,5] triazine.
25. The compound of claim 1, wherein the compound is: y 2, 4-bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- (3-dimethylaminopropyl) amino- [1,3,5] triazine, 2,4, 6-tris (4-amino-2-methylquinolin-6-yl) amino- [1,3, 5] triazine, 2, 4-bis ( -amino-2-methylquinolin-6-yl ) amino-6- (4- dimethylamino-2-methylquinolin-6-yl) amino- [1,3,5] triazine, 2, -bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- (l-methylpiperazin-4-yl) -[1,3,5] triazine, 2, 4-bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- (pyridin-4-yl) oxy- [1,3,5] triazine, 2, 4-bis (4-amino-2-methylquinolin-6-yl) amino-6- (quinolin- 2-yl) thio- [1,3,5] triazine, 2, 4-bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- phenyl- [1,3,5] triazine, 2, 4-bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- [1- (2-dipropylaminoethyl ) piperazin-4-yl] - [1,3,5] triazine, 180 158056/2 2, -bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- { [1-2- (2-hydroxyethyl) oxyethyl] piperazin-4-yl } - [1,3,5] triazine, 2, 4-bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- [2 (S) - (pyrrolidin-l-yl) methylpyrrolidin-l-yl] - [1,3,5] triazine, 2, 4-bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- (quinolin-2-yl) thio- [1,3,5] triazine, 2, -bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- ( 1- methylhomopiperazin-4-yl) -[1,3,5] triazine, 2, -bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- [1- (3-dimethylaminopropyl) piperazin-4-yl] -[1,3, 5] triazine, 2, 4-bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- [N- (l-methylpiperidin-4-yl) -N-methylamino] -[1,3,5] triazine, 2, -bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6-{ 1- [3- (pyrrolidin-l-yl) propylhomopiperazin-4-yl ) - [1, 3, 5] triazine, or 2, 4-bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- [1- (pyridin-4-yl) piperazin-4-yl] -[1,3,5] triazine.
26. The compound of claim 1, wherein the compound is: 2, 4-bis ( 4-dimethylamino-2-methylquinolin-6-yl ) amino-6- (l-methylpiperazin-4-yl) - [1, 3, 5] triazine, 2, 4-bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- (quinolin-2-yl ) thio- [1,3,5] triazine, 2, -bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- (l-methylhomopiperazin-4-yl) -[1,3,5] triazine, 2, -bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- [1- (3-dimethylaminopropyl)piperazin-4-yl] - [1,3,5] triazine, 2, 4-bis (4-dimethylamino-2-methylquinolin-6-yl) amino-6- [N- (l-methylpiperidin-4-yl) -N-methylamino] - [1,3,5] triazine, 2, -bis ( 4-dimethylamino-2-methylquinolin-6-yl ) amino-6- { 1- [3- (pyrrolidin-l-yl) propylhomopiperazin-4-yl) - [1, 3, 5] triazine, or 181 158056/2 2, -bis ( 4-dimethylamino-2-methylquinolin-6-yl ) amino-6- [1- (pyridin-4-yl) piperazin-4-yl] -[1,3,5] triazine.
27. A compound selected from the group consisting of: N- (4-amino-2-methyl-quinolin-6-yl) -N ' - ( 2-chloro-phenyl ) - N"- (4-dimethylamino-2-methyl-quinolin-6-yl) - [1, 3, 5] triazine-2, 4, 6-triamine; N- ( 4-amino-2-methyl-quinolin-6-yl) -N ' - (2-chloro-phenyl) - N"-pyridin-4-yl- [1, 3, 5] triazine-2, 4, 6-triamine; N- (4-amino-2-methyl-quinolin-6-yl) - ' - (2-chloro-phenyl) - N"- (2-dimethylamino-ethyl) -[1,3, 5] triazine-2, 4 , 6- triamine; N- (4-amino-2-methyl-quinolin-6-yl) -N ' - (2-chloro-phenyl) - N"- ( 3-dimethylamino-propyl ) -[1,3, 5] triazine-2, , 6- triamine; N- (4-amino-2-methyl-quinolin-6-yl) - ' - (2-chloro-phenyl) - N"- (l-methyl-piperidin-4-yl) - [1, 3, 5] triazine-2 , 4 , 6- triamine; N*6*- [4- (2-chloro-phenylamino) -6- ( 4-methyl-piperazin-l- yl) -[1,3, 5] triazin-2-yl] -2-methyl-quinoline-4 , 6-diamine; N, N ' -bis- (4-amino-2-methyl-quinolin-6-yl) -N"- (4-chloro- phenyl) -[1,3, 5] triazine-2, 4, 6-triamine; N, N ' -2 , -bis- (4-amino-2-methyl-quinolin-6-yl) amino-6- ( 4- chloro-phenoxy) -[1,3, 5] triazine; and N, ' -2, -bis- (4-amino-2-methyl-quinolin-6-yl) amino- 6- (4- chloro-phenyl) thio- [1,3,5] triazine.
28. A pharmaceutical composition for human use comprising a compound of claim 1 and one or more pharmaceutically acceptable excipients.
29. A pharmaceutical composition comprising, as active ingredient, one or more compounds according to claim 1.
30. A pharmaceutical composition comprising, as active ingredient, one or more compounds according to claim 24. 182 158056/2
31. A pharmaceutical composition comprising, as active ingredient, one or more compounds according to claim 25.
32. A pharmaceutical composition comprising, as active ingredient, one or more compounds according to claim 26. P-6178-IL
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