US 2020/0253996 A1 · TCTP INHIBITING AGENTS FOR THE TREATMENT OF PROLIFERATIVE DISEASES, INFECTIOUS DISEASES, ALLERGIES, INFLAMMATIONS AND/OR ASTHMA

Tctp inhibiting agents for the treatment of proliferative diseases, infectious diseases, allergies, inflammations and/or asthma

AssigneesUniversite Paris-Sud, Centre National de la Recherche Scientifique (CNRS), Institut National De La Sante Et De La Recherche Medicale (Inserm), Institut Gustave Roussy

InventorsSamir MESSAOUDI, Mouad ALAMI, Jean-Daniel BRION, Amélie CHABRIER, Adam TELERMAN, Robert AMSON

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Abstract

The present invention relates to the compounds of formula (I) below: wherein: X represents an oxygen atom, a sulfur atom, a nitrogen atom or a CH radical, The bond X—Y and Y are absent if X represents an oxygen or sulfur atom, the bond X—Y and Y are present if X represents a nitrogen atom or a CH radical, When present, Y represents a group R if X represents a nitrogen atom, a hydrogen atom or a group —NR1R2 if X represents a CH radical, (Het)Ar is an aromatic ring selected from the group consisting of aryl and heteroaryl groups, R3, R4, R5, R6 represent, independently of one another, a hydrogen atom, a halogen atom, a —NR12R13, a —SR14 group, a —OR14 group or a —CF3 group, When Y is —NR1R2, the groups —NR1R2 and (Het)Ar are in the cis-conformation, or a pharmaceutically acceptable salt thereof, for use in the treatment of proliferative diseases, infectious diseases, allergies, inflammation and/or asthma.

Claims21

Dependent claims

1-13. (canceled)

A method for treating a proliferative or infectious disease, an allergy, an inflammation and/or an asthma comprising administering to a patient in need thereof an effective amount of a compound of the following formula (I):

Wherein
X represents an oxygen atom, a sulfur atom, a nitrogen atom or a CH radical,
The bond X—Y and Y are absent if X represents an oxygen or sulfur atom, the bond X—Y and Y are present if X represents a nitrogen atom or a CH radical,
When present, Y represents
a group R if X represents a nitrogen atom,
wherein R represents a hydrogen atom, a C1 to C6 alkyl group, an aryl group, a heteroaryl group, a (C2-C6)alkenyl group, a (C2-C6)alkynyl group or an acyl group,
a hydrogen atom or a group —NR1R2 if X represents a CH radical,
wherein R1 and R2 represent, independently of one another, a hydrogen atom, a C1 to C6 alkyl group, an aryl group, a heteroaryl group, a (C2-C6)alkenyl group, a (C2-C6)alkynyl group or an acyl group, or R1 and R2, together with the nitrogen atom carrying them, form a 5- or 6-membered heterocyclic ring,
(Het)Ar is an aromatic ring selected from the group consisting of aryl and heteroaryl groups,
said aromatic ring may be substituted by one or more groups selected from a halogen atom, a —COOR7 group, a —CONR8R9 group, a C1 to C6 alkyl group, a —SR10 group, a CF3 group, a formyl group, an OR11 group, a (C2-C6)alkenyl group,
with R7 representing a hydrogen atom, a C1 to C6 alkyl group, an aryl group, a heteroaryl group or a sugar residue,
with R8 and R9 representing, independently of one another, a hydrogen atom, a C1 to C6 alkyl group, an aryl group, a heteroaryl group, a (C2-C6)alkenyl group, a (C2-C6)alkynyl group, a sugar residue, an amino acid residue, a peptide residue or R8 and R9, together with the nitrogen atom carrying them, form a 5- or 6-membered heterocyclic ring,
with R10 representing a hydrogen atom, a C1 to C6 alkyl group, an aryl group, a heteroaryl group, a sugar residue, a peptide residue comprising at least one cysteine or —SR10 represents a cysteine residue,
with R11 representing a hydrogen atom, a C1 to C6 alkyl group, an aryl group or a benzyl group,
R3, R4, R5, R6 represent, independently of one another, a hydrogen atom, a halogen atom, an —NR12R13 group, a —SR14 group, an —OR14 group or a —CF3 group,
where R12 and R13 represent independently of one another a hydrogen atom, a C1 to C6 alkyl group, an aryl group, a heteroaryl group, a (C2-C6)alkenyl group, a (C2-C6)alkynyl group or an acyl group, or R12 and R13, together with the nitrogen atom carrying them, form a 5- or 6-membered heterocyclic ring,
with R14 representing a hydrogen atom, a C1-C6 alkyl group, an aryl group, a heteroaryl group, a sugar residue, an amino acid residue or a peptide residue,
When Y represents a group —NR1R2, the groups —NR1R2 and (Het)Ar are in the cis-conformation,
the alcohol functions of the sugar residue and the amine functions of the amino acid residue, of the cysteine residue or of the peptide residue being in their free or protected form,
or a pharmaceutically acceptable salt thereof,
with the exception of the compound 4-(3,4-dichloro-phenyl)-1,2,3,4-tetrahydronaphthalene-1-ylamine or a pharmaceutically acceptable salt thereof.

18 more elements

A method for inhibiting translationally controlled tumor protein TCTP comprising administering to a patient in need thereof an effective amount of a compound of the following formula (I):

Wherein
X represents an oxygen atom, a sulfur atom, a nitrogen atom or a CH radical,
The bond X—Y and Y are absent if X represents an oxygen or sulfur atom, the bond X—Y and Y are present if X represents a nitrogen atom or a CH radical,
When present, Y represents
a group R if X represents a nitrogen atom,
wherein R represents a hydrogen atom, a C1 to C6 alkyl group, an aryl group, a heteroaryl group, a (C2-C6)alkenyl group, a (C2-C6)alkynyl group or an acyl group,
a hydrogen atom or a group —NR1R2 if X represents a CH radical,
wherein R1 and R2 represent, independently of one another, a hydrogen atom, a C1 to C6 alkyl group, an aryl group, a heteroaryl group, a (C2-C6)alkenyl group, a (C2-C6)alkynyl group or an acyl group, or R1 and R2, together with the nitrogen atom carrying them, form a 5- or 6-membered heterocyclic ring,
(Het)Ar is an aromatic ring selected from the group consisting of aryl and heteroaryl groups,
said aromatic ring may be substituted by one or more groups selected from a halogen atom, a —COOR7 group, a —CONR8R9 group, a C1 to C6 alkyl group, a —SR10 group, a CF3 group, a formyl group, an OR11 group, a (C2-C6)alkenyl group,
with R7 representing a hydrogen atom, a C1 to C6 alkyl group, an aryl group, a heteroaryl group or a sugar residue,
with R8 and R9 representing, independently of one another, a hydrogen atom, a C1 to C6 alkyl group, an aryl group, a heteroaryl group, a (C2-C6)alkenyl group, a (C2-C6)alkynyl group, a sugar residue, an amino acid residue, a peptide residue or R8 and R9, together with the nitrogen atom carrying them, form a 5- or 6-membered heterocyclic ring,
with R10 representing a hydrogen atom, a C1 to C6 alkyl group, an aryl group, a heteroaryl group, a sugar residue, a peptide residue comprising at least one cysteine or —SR10 represents a cysteine residue,
with R11 representing a hydrogen atom, a C1 to C6 alkyl group, an aryl group or a benzyl group,
R3, R4, R5, R6 represent, independently of one another, a hydrogen atom, a halogen atom, an —NR12R13 group, a —SR14 group, an —OR14 group or a —CF3 group,
where R12 and R13 represent independently of one another a hydrogen atom, a C1 to C6 alkyl group, an aryl group, a heteroaryl group, a (C2-C6)alkenyl group, a (C2-C6)alkynyl group or an acyl group, or R12 and R13, together with the nitrogen atom carrying them, form a 5- or 6-membered heterocyclic ring,
with R14 representing a hydrogen atom, a C1-C6 alkyl group, an aryl group, a heteroaryl group, a sugar residue, an amino acid residue or a peptide residue,
When Y represents a group —NR1R2, the groups —NR1R2 and (Het)Ar are in the cis-conformation,
the alcohol functions of the sugar residue and the amine functions of the amino acid residue, of the cysteine residue or of the peptide residue being in their free or protected form,
or a pharmaceutically acceptable salt thereof,
with the exception of the compound 4-(3,4-dichloro-phenyl)-1,2,3,4-tetrahydronaphthalene-1-ylamine or a pharmaceutically acceptable salt thereof.

18 more elements

Dependencies are inferred from the claim text.