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US 11,299,506 B2Granted
Acylnucleoside phosphonates, prodrugs thereof and use thereof as medicament
AssigneesUniversite De Montpellier, Centre National De La Recherche Scientifique, Ecole Nationale Superieure De Chimie De Montpellier
InventorsSuzanne Peyrottes, Christian Perigaud, Sharon Wein-Grataud
Life of this patent
Estimating the term…
Abstract
Chemical compounds are provided belonging to the group of nucleotide analogues. More specifically, acylnucleoside phosphonate compounds are disclosed and also their method of preparation and their use as medicaments, in particular for the prevention and/or the treatment of diseases caused by infection by an organism that is auxotrophic for purines, such as Plasmodium falciparum. Also disclosed are pharmaceutical compositions containing such compounds.
Claims13
A method for treatment of an infection caused by an organism auxotrophic for purines, said organism being selected from bacteria and protozoans,
- wherein said infection is caused by an agent selected from:
- Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, Plasmodium knowlesi, Giardia lamblia, Helicobacter pylori, Mycobacterium tuberculosis, Escherichia coli, Trypanosoma brucei, Babesia divergens, Babesia canis and Toxoplasma gondii, and
- wherein said method comprises administering to a subject in need thereof a compound having the following general formula (I):
- in which
- A represents a heterocycle of formula (IIA) or a heterocycle of formula (IIB), as below:
- in which:
- W1 represents an oxygen atom or a sulfur atom;
- W2 represents a halogen atom, a —OR5 group, a —SR5 group, a —NHR5 group or a —N(R5)2 group;
- X1 represents a nitrogen atom or a —CH— group;
- X2 represents a nitrogen atom, a —CR1 group or a —C═O group;
- X3 represents a nitrogen atom or a —CH— group;
- X4 represents a nitrogen atom, a —CR2 group or a —C═O group;
- R1 represents:
- a hydrogen atom, or
- a halogen atom, or
- a group selected from:
- a —NHR5 group,
- a —N(R5)2 group,
- a —OR5 group,
- a —SR5 group,
- a C1-C6 alkyl group,
- an aryl group,
- a heteroaryl group;
- R2 represents:
- a hydrogen atom, or
- a halogen atom, or
- a group selected from:
- a —NHR5 group,
- a —N(R5)2 group,
- a —OR5 group,
- a C1-C6 alkyl group,
- an aryl group,
- a heteroaryl group;
- a C2-C6 alkenyl group,
- a C2-C6 alkynyl group,
- an aryl (C1-C6) alkyl group,
- a (C1-C6) alkylaryl group,
- a heteroaryl(C1-C6)alkyl group;
- R3 and R4, which are identical or different, each represent, independently of one another:
- a —OR6 group, or
- a —NHR7 group, or
- a —N(R7)2 group;
- R5 represents:
- a hydrogen atom
- a C1-C6 alkyl group,
- a C2-C6 alkenyl group,
- a C2-C6 alkynyl group,
- an aryl group,
- a C1-C6 acyl group,
- an aryl(C1-C6)alkyl group,
- said groups optionally containing one or more heteroatoms;
- R6 represents:
- a hydrogen atom, a sodium atom or a lithium atom, or
- a group selected from:
- an ammonium group,
- a —N(RaRbRcRd)+ group with Ra, Rb, Rc and Rd, which are identical or different, each representing a hydrogen atom or a C1-C4 alkyl group,
- an aryl group,
- a S—(C1-C12)alkyl-2-dithioethyl group, said alkyl group optionally including at least one heteroatom,
- a S—(C1-C12)aryl-2-dithioethyl group, said aryl group optionally including at least one heteroatom,
- a S—(C1-C6)acyl-2-thioethyl group, said acyl group optionally including at least one heteroatom,
- a (C1-C6)alkyloxy(C1C6)alkyl ester group,
- an alkoxy(C1-C6)carbonyloxymethyl ester group,
- a C12-C20 alkyl group optionally including at least one heteroatom,
- R7 represents:
- a C1-C6 alkyl chain,
- an aryl group, or
- an amino acid residue, an amino acid ester derivative or an amino acid amide derivative;
- n is a whole number equal to 0, 1 or 2;
- Y represents a substituent selected from:
- a halogen atom, a —OR5 group, a —SR5 group, a —NHR5 group and a —N(R5)2 group;
- C* represents a chiral carbon atom,
- or a stereoisomer or pharmaceutically acceptable salt thereof.
69 more elements
A compound having the following general formula (I):
- in which
- A represents a heterocycle having formula (IIA) as below:
- in which:
- W1 represents an oxygen atom or a sulfur atom;
- X1 represents a nitrogen atom or a —CH— group;
- X2 represents a nitrogen atom, a —CR1 group or a —C═O group;
- X3 represents a nitrogen atom or a —CH— group;
- X4 represents a nitrogen atom, a —CR2 group or a —C═O group;
- R1 represents:
- a hydrogen atom, or
- a halogen atom, or
- a group selected from:
- a —NHR5 group,
- a —N(R5)2 group,
- a —OR5 group,
- a —SR5 group,
- a C1-C6 alkyl group,
- an aryl group,
- a heteroaryl group;
- R2 represents:
- a hydrogen atom, or
- a halogen atom, or
- a group selected from:
- a —NHR5 group,
- a —N(R5)2 group,
- a —OR5 group,
- a C1-C6 alkyl group,
- an aryl group,
- a heteroaryl group;
- a C2-C6 alkenyl group,
- a C2-C6 alkynyl group,
- an aryl (C1-C6)alkyl group,
- a (C1-C6)alkylaryl group,
- a heteroaryl(C1-C6)alkyl group;
- R3 and R4, which are identical or different, each represent, independently of one another:
- a —OR6 group, or
- a —NHR7 group, or
- a —N(R7)2 group;
- R5 represents:
- a hydrogen atom
- a C1-C6 alkyl group,
- a C2-C6 alkenyl group,
- a C2-C6 alkynyl group,
- an aryl group,
- a C1-C6 acyl group,
- an aryl(C1-C6)alkyl group,
- said groups optionally containing one or more heteroatoms;
- R6 represents:
- a hydrogen atom, a sodium atom or a lithium atom, or
- a group selected from:
- an ammonium group
- a —N(RaRbRcRd)+ group with Ra, Rb, Rc and Rd, which are identical or different, each representing a hydrogen atom or a C1-C4 alkyl group,
- an aryl group,
- a S—(C1-C12)alkyl-2-dithioethyl group, said alkyl group optionally including at least one heteroatom,
- a S—(C1-C12)aryl-2-dithioethyl group, said aryl group optionally including at least one heteroatom,
- a S—(C1-C6)acyl-2-thioethyl group, said acyl group optionally including at least one heteroatom,
- a (C1-C6)alkyloxy(C1C6)alkyl ester group,
- an alkoxy(C1-C6)carbonyloxymethyl ester group,
- a C12-C20 alkyl group optionally including at least one heteroatom,
- R7 represents:
- a C1-C6 alkyl chain,
- an aryl group, or
- an amino acid residue, an amino acid ester derivative or an amino acid amide derivative;
- n is a whole number equal to 0, 1 or 2;
- Y represents a substituent selected from:
- a chlorine atom, bromine atom, iodine atom, a —OR5 group, a —SR5 group, a —NHR5 group and a —N(R5)2 group;
- C* represents a chiral carbon atom.
64 more elements
A pharmaceutical composition including at least one pharmaceutically acceptable excipient, and at least one compound having the following general formula (I):
- in which
- A represents a heterocycle having formula (IIB) as below:
- in which:
- W2 represents a halogen atom, a —OR5 group, a —SR5 group, a —NHR5 group or a —N(R5)2 group;
- X1 represents a nitrogen atom or a —CH— group;
- X2 represents a nitrogen atom, a —CR1 group or a —C═O group;
- X3 represents a nitrogen atom or a —CH— group;
- X4 represents a nitrogen atom, a —CR2 group or a —C═O group;
- R1 represents:
- a hydrogen atom, or
- a halogen atom, or
- a group selected from:
- a —NHR5 group,
- a —N(R5)2 group,
- a —OR5 group,
- a —SR5 group,
- a C1-C6 alkyl group,
- an aryl group,
- a heteroaryl group;
- R2 represents:
- a hydrogen atom, or
- a halogen atom, or
- a group selected from:
- a —NHR5 group,
- a —N(R5)2 group,
- a —OR5 group,
- a C1-C6 alkyl group,
- an aryl group,
- a heteroaryl group;
- a C2-C6 alkenyl group,
- a C2-C6 alkynyl group,
- an aryl (C1-C6)alkyl group,
- a (C1-C6)alkylaryl group,
- a heteroaryl(C1-C6)alkyl group;
- R3 and R4, which are identical or different, each represent, independently of one another:
- a —OR6 group, or
- a —NHR7 group, or
- a —N(R7)2 group;
- R5 represents:
- a hydrogen atom
- a C1-C6 alkyl group,
- a C2-C6 alkenyl group,
- a C2-C6 alkynyl group,
- an aryl group,
- a C1-C6 acyl group,
- an aryl(C1-C6)alkyl group,
- said groups optionally containing one or more heteroatoms;
- R6 represents:
- a hydrogen atom, a sodium atom or a lithium atom, or
- a group selected from:
- an ammonium group
- a —N(RaRbRcRd)+ group with Ra, Rb, Rc and Rd, which are identical or different, each representing a hydrogen atom or a C1-C4 alkyl group,
- an aryl group,
- a S—(C1-C12)alkyl-2-dithioethyl group, said alkyl group optionally including at least one heteroatom,
- a S—(C1-C12)aryl-2-dithioethyl group, said aryl group optionally including at least one heteroatom,
- a S—(C1-C6)acyl-2-thioethyl group, said acyl group optionally including at least one heteroatom,
- a (C1-C6)alkyloxy(C1C6)alkyl ester group,
- an alkoxy(C1-C6)carbonyloxymethyl ester group,
- a C12-C20 alkyl group optionally including at least one heteroatom,
- R7 represents:
- a C1-C6 alkyl chain,
- an aryl group, or
- an amino acid residue, an amino acid ester derivative or an amino acid amide derivative;
- n is a whole number equal to 0, 1 or 2;
- Y represents a substituent selected from:
- a chlorine atom, bromine atom, iodine atom, a —OR5 group, a —SR5 group, a —NHR5 group and a —N(R5)2 group;
- C* represents a chiral carbon atom,
- with the exception of the compounds in which:
- W2 represents the —NH2 group;
- X1 represents a nitrogen atom;
- X2 represents a —CR1 group, R1 representing a hydrogen atom;
- X3 represents a nitrogen atom;
- X4 represents a —CR2 group, R2 representing a hydrogen atom;
- n is equal to 1;
- Y represents a hydrogen atom, hydroxyl group or an —NH2 group;
- the chiral carbon C* has configuration R or S, and
- R3 and R4 each represent a —OR6 group in which R6 is a sodium atom.
74 more elements
Dependencies are inferred from the claim text.