Back to results
US 9,540,356 B2Granted
Compounds having a protective activity against toxins with intracellular activity
AssigneesCommissariat A L'energie Atomique Et Aux Energies Alternatives, Institut Curie, Centre National De La Recherche Scientifique
InventorsDaniel Gillet, Julien Barbier, Ludger Johannes, Jean-Christophe Cintrat, Romain Noel
Life of this patent
Estimating the term…
Abstract
The present invention concerns a new family of 2,3-dihydroquinazolin-4(1H)-one compounds of general formula (I), and the use thereof as inhibitors of the toxic effects of toxins with intracellular activity, such as ricin or Shiga toxin, for example, using retrograde transport to intoxicate cells.
Claims12
A compound of formula (I):
- wherein:
- R1 represents a hydrogen atom, a halogen atom or an alkoxy radical having from 1 to 3 carbon atoms;
- R2 represents a phenyl ring, optionally substituted with:
- a phenyl radical, a halogen atom, an —SO2-phenyl group or an —S—X or —O—X group, X being an alkyl radical having from 1 to 4 carbon atoms, an alkoxy having from 1 to 4 carbon atoms or a PEG of formula —(CH2—CH2—O)n—R with n being 1 to 10, and R is a hydrogen atom or a methyl radical, or a —CO—Y or —CO—O—Y group, Y being a hydrogen atom, an alkyl radical having from 1 to 4 carbon atoms, a phenyl ring or an allyl (—CH2—CH═CH2) group;
- R3 represents a thiophene ring substituted on C5′ of the thiophene, the quinazolinone ring being bonded to C2′ of the thiophene, with
- an alkyl radical having from 1 to 3 carbon atoms;
- a halogen atom;
- a phenyl radical optionally substituted with an alkoxy radical having from 1 to 3 carbon atoms, a —CN group, an —NO2 group or a —COX or —COOX group with X an alkyl radical having from 1 to 4 carbon atoms, or a combination of these substituents;
- an —SY group, Y being an alkyl radical having from 1 to 4 carbon atoms or a phenyl radical;
- a —CN group;
- a —CH2—N3 group;
- an aromatic heterocycle having 5 or 6 atoms selected from the group consisting of a furan, a thiophene, a pyrrole, a pyrroline, a pyrrolidine, a dioxolane, oxazole, a thiazole, an imidazole, an imidazoline, an imidazolidine, a pyrazole, an isoxazole, an isothiazole, a pyran, a pyridine, a piperidine, a dioxane, a morpholine, a pyridazine, a pyrimidine and a pyrazine ring, optionally substituted with at least one alkyl radical having from 1 to 3 carbon atoms, a —CH2—N3, group, or both;
- R4 represents a hydrogen atom or a methyl radical;
- and
- with the exclusion of 3-(4-chlorophenyl)-2-(5-methylthiophen-2-yl)-2,3-dihydroquinazolin-4(1H)-one and of the compound such that R1 is a hydrogen atom, R2 a phenyl radical, R3 a 5-methylthiophen-2-yl radical and R4 a hydrogen atom.
12 more elements
A method for preventing and/or treating disorders induced by toxins with an intracellular mode of a using retrograde transport, the method comprising administering to a subject in need thereof an effective amount of at least one compound of formula (I):
- to a subject in need thereof,
- wherein:
- R1 represents a hydrogen atom, a halogen atom or an alkoxy radical having from 1 to 3 carbon atoms;
- R2 is a phenyl ring, optionally substituted with:
- a phenyl radical, a halogen atom, an —SO2-phenyl group or an —S—X or —O—X group, X being an alkyl radical having from 1 to 4 carbon atoms, alkoxy having from 1 to 4 carbon atoms;
- or a PEG of formula —(CH2—CH2—O)n—R with n being 1 to 10, and R represents a hydrogen atom or a methyl radical, or a —CO—Y or —CO—O—Y group, Y being a hydrogen atom, an alkyl radical having from 1 to 4 carbon atoms, a phenyl ring or an allyl (—CH2—CH═CH2) group;
- R3 represents a thiophene ring substituted on C5′ of the thiophene, the quinazolinone ring being bonded to C2′ of the thiophene, with
- an alkyl radical having from 1 to 3 carbon atoms;
- a halogen atom;
- a phenyl radical optionally substituted with an alkoxy radical having from 1 to 3 carbon atoms, a —CN group, an —NO2 group or a —COX or —COOX group with X an alkyl radical having from 1 to 4 carbon atoms, or a combination of these substituents;
- an —SY group, Y being an alkyl radical having from 1 to 4 carbon atoms or a phenyl radical;
- a —CN group;
- a —CH2—N3 group;
- an aromatic heterocycle having 5 or 6 atoms selected from the group consisting of a furan, a thiophene, a pyrrole, a pyrroline, a pyrrolidine, a dioxolane, oxazole, a thiazole, an imidazole, an imidazoline, an imidazolidine, a pyrazole, an isoxazole, an isothiazole, a pyran, a pyridine, a piperidine, a dioxane, a morpholine, a pyridazine, a pyrimidine and a pyrazine ring, optionally substituted with at least one alkyl radical having from 1 to 3 carbon atoms, a —CH2—N3 group, or both;
- and
- R4 represents a hydrogen atom or a methyl radical;
- with the exclusion of the compound such that R1 is a hydrogen atom, R2 a phenyl radical, R3 a 5-methylthiophen-2-yl radical and R4 a hydrogen atom.
14 more elements
Dependencies are inferred from the claim text.