Back to results
US 12,612,354 B2Granted
Cyclopentenones derivatives and their use as antibiotics
AssigneeCentre National de la Recherche Scientifique (CNRS)
InventorsJamal-Eddine Ouazzani Chahdi, Géraldine Le Goff, Jean-Félix Dallery, Jean-François Betzer, Arnaud Voituriez, Angela Marinetti, Fanny Cacheux
Life of this patent
Estimating the term…
Abstract
The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt and/or solvate thereof, for use as a drug, especially as an antibiotic. The present invention also relates to a pharmaceutical composition comprising said compound of formula (I) and at least one pharmaceutically acceptable excipient. The present invention further concerns a method of preparation of a compound of formula (I′).
Claims20
A method for treating bacterial infections, comprising administering to a patient in need thereof an effective amount of a compound of the following formula (1) or a pharmaceutical composition comprising a compound of formula (1) and a pharmaceutically acceptable excipient:
- wherein
- X is O or NH,
- R1 is H, C(═O)—C1-C6 alkyl, C(═O)—O—C1-C6 alkyl, Si(C1-C6 alkyl)3, or a phenyl optionally substituted with one or more substituents, selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl,
- R2 is H or CH2OR4, R4 being H, C1-C6 alkyl, C1-C6 alkyl-substituted by an aryl group optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl or C(═O)R5, R5 being an aryl optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORI, CO2Rd, CONReRf, ORg, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl or a heterocycle optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl,
- or R1 and R2 together represent a heterocycle optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf ORg, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl, and R3 is an aryl optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl or a heteroaryl optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl, as well as any stereoisomers, diastereoisomers, enantiomers and mixtures thereof and any pharmaceutically acceptable salts and/or solvates thereof, provided in said compound R3 and X—R1 groups are in trans position.
2 more elements
A pharmaceutical composition comprising a compound of the following formula (1)
- wherein
- X is O or NH,
- R1 is H, a phenyl optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl, C(═O)—C1-C6 alkyl, C(═O)—O—C1-C6 alkyl or Si(C1-C6 alkyl)3, R2 is H or CH2OR4, R4 being H, C1-C6 alkyl, C1-C6 alkyl-aryl optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl or C(═O)R5, R5 being an aryl optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl or a heterocycle optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl,
- or R1 and R2 together represent a heterocycle optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORo, CO2Rd, CONReRf, OR9, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl, and
- R3 is an aryl optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl or a heteroaryl optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, OR9, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl
- as well as any stereoisomers, diastereoisomers, enantiomers and mixtures thereof and any pharmaceutically acceptable salts and/or solvates thereof, provided in said compound R3 and X—R1 groups are in trans position,
- and a pharmaceutically acceptable excipient.
4 more elements
A compound of the following formula (I):
- wherein
- X is O or NH,
- R1 is H, a phenyl optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaNRb, CORc, CO2Rd, CONReRf, ORg, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl, C(═O)—C1-C6 alkyl, C(═O)—O—C1-C6 alkyl or Si(C1-C6 alkyl)3,
- R2 is CH2OR4, R4 being H, C1-C6 alkyl-aryl or C(═O)R5 optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, and CN wherein Ra to Rg are, indecently of one another, H or C1-C6 alkyl R5 being an aryl optionally substate with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl or a heterocycle, optionally substate with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, and ON wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl and
- R3 is an aryl optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, and ON wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl or a heteroaryl optionally substituted with one or more substituents selected from halogen, C1-C6 alkyl, C3-C7 cycloalkyl, C1-C6 haloalkyl, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, and CN wherein Ra to Rg are, independently of one another, H or C1-C6 alkyl,
- as well as any stereoisomers, diastereoisomers, enantiomers and mixtures thereof and any pharmaceutically acceptable salts and/or solvates thereof, provided in said compound R3 and X—R1 groups are in trans position, with the proviso that said compound is not:
3 more elements
A method for the preparation of a compound of formula (I′):
- wherein
- R3 is an optionally substituted aryl or an optionally substituted heteroaryl,
- or a pharmaceutically acceptable salt and/or solvate thereof, said method comprising the following steps:
- (a) reacting a compound of formula (II-B)
- in which R3 is an optionally substituted aryl or an optionally substituted heteroaryl,
- in presence of a C1-C6 alcohol, and optionally a Lewis acid, under a micro wave heating,
- (b) if necessary, isolating the diastereoisomer of formula (I′).
4 more elements
Dependencies are inferred from the claim text.