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US 9,428,530 B2Granted
Derivatives of oxazaphosphorines that are pre-activated, use and method of preparation
AssigneeInstitut Gustave Roussy
InventorsAngelo Paci, Thierry Martens, Michael Rivard, Patrick Couvreur, Didier Desmaele, Joachim Caron
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Abstract
The present invention relates to novel derivatives of oxazaphosphorines that are pre-activated, to the methods for preparing same, to the pharmaceutical compositions containing same and to the therapeutic use thereof, in particular for treating cancer.
Claims20
A compound of formula (I)
- wherein:
- X is O or S;
- R1, and R2 are independently H, —(CH2)2—Cl or —CH(CH3)—CH2—Cl with proviso that at least one group among R1 and R2 is —(CH2)2—Cl or —CH(CH3)—CH2—Cl;
- R3 is —(CH2)2—Cl or —CH(CH3)—CH2—Cl;
- R4 is a vectorization or formulation group comprising a linear or branched, unsaturated hydrocarbon group of 5 to 30 carbon atoms, optionally substituted by one or more substituents selected from —OR, —C(O)OR, —OC(O)R, —OC(O)OR, —C(O)R, —NRR′, —C(O)NRR′, —NC(O)R, —NRC(O)R′, —SR, halogen, cyano (—CN), aryl, heteroaryl, alkyl and arylalkyl, wherein R is hydrogen or a C1-C3 alkyl and R′ is hydrogen or a C1-C3 alkyl;
- or a pharmaceutically acceptable salt thereof.
3 more elements
A method for preparing an oxazaphosphorine of formula (I)
- wherein:
- X is O or S;
- R1, and R2 are independently H, —(CH2)2—Cl or —CH(CH3)—CH2—Cl with proviso that at least one group among R1 and R2 is —(CH2)2—Cl or —CH(CH3)—CH2—Cl;
- R3 is —(CH2)2—Cl or —CH(CH3)—CH2—Cl;
- R4 is a vectorization or formulation group comprising a linear or branched, unsaturated hydrocarbon group of 5 to 30 carbon atoms, optionally substituted by one or more substituents selected from the group consisting of —OR, —C(O)OR, —OC(O)R, —OC(O)OR, —C(O)R, —NRR′, —C(O)NRR′, —NC(O)R, —NRC(O)R′, —SR, halogen, cyano (—CN), aryl, heteroaryl, arylalkyl;
- wherein R is a hydrogen or a C1-C3 alkyl and R′ is a hydrogen or a C1-C3 alkyl;
- said method comprising:
- providing a compound of formula (II)
- wherein R1, R2 and R3 are as defined in formula (I);
- and
- reacting the compound of formula (II) with R4-XH, wherein X and R4 are defined as in formula (I), in the presence of a Lewis acid.
8 more elements
Dependencies are inferred from the claim text.