US 2022/0259249 A1 · INHIBITORS OF ANTIBIOTIC RESISTANCE MEDIATED BY ARNT

Abstract

The present invention relates to diterpene compounds of general formula (I) capable of contrasting the antibiotic-resistance mediated by the ArnT enzyme, to their use as a medicament, in particular for use as an adjuvant of an antibiotic therapy in the treatment of antibiotic-resistant bacterial infections. The invention relates also to associations of one or more of the compounds of formula (I) with at least another active ingredient, in particular an antibacterial agent and/or an antibiotic, and compositions comprising one or more compounds of formula (I) or the association according to the present invention and at least one pharmaceutically acceptable excipient and/or carrier as well as to products, in particular medical devices, comprising at least a compound, an association or a composition according to the present invention. Moreover, the invention relates to the use of compounds of formula (I) to sensitize a bacterium to an antibacterial agent or an antibiotic, for example, colistin (polymyxin E) or polymyxin B and to an in vivo or in vitro method for sensitizing a bacterium to an antibacterial agent or an antibiotic comprising the exposure of said bacterium to one or more compounds of formula (I) together with colistin.

Claims32

Dependent claims

An adjuvant in antibiotic therapy comprising a compound of formula (I):

wherein
R1 and R2 are the same or different and independently selected among:
hydrogen, C(RA)3, ORA, C(═O)RA, C(═O)ORA, CH2ORA, CH2OC(═O)RA, CH2OC(═O)ORA, CH2OC(═O)(CH2)nC(═O)ORA with n=0, 1 or 2, CH2N(RA)2, C(═O)N(RA)2, CH2NHC(═O)RA and CH2C(═O)N(RA)2;
where RA is selected among:
hydrogen, alkyl, hydroxyl, monosaccharide, disaccharide and CH2-formula (I);
R3 is hydrogen, C(RB)3 or ORB;
where RB is selected among:
hydrogen, alkyl, hydroxyl, and disaccharide;
the endocyclic symbol represents a single or double bond and, when it represents a double bond, the exocyclic symbol binding R4 to the carbocycle represents a single bond;
R4 is hydrogen when the exocyclic symbol binding R4 to the carbocycle represents a single bond;
or
R4 is oxygen or methylene when the exocyclic symbol binding R4 to the carbocycle represents a double bond;
and pharmaceutically acceptable salts.

10 more elements

Dependencies are inferred from the claim text.

Inhibitors of antibiotic resistance mediated by arnt

Life of this patent

Inhibitors of antibiotic resistance mediated by arnt

Life of this patent

Abstract

Claims32