New heterocyclic compounds active as inhibitors of beta-lactamases.

摘要

Use of compounds of general formula (I): wherein: (I) R1 represents a hydrogen atom, a COOH radical, CN, COOR, CONR6, R7, (CH2) N'R or R is selected from the group constituted by an alkyl radical comprising from 1 to 6 carbon atoms, optionally substituted by a pyridyl or carbamoyl radical, a radical -CH2-alkenyl comprising in total from 3 to 9 carbon atoms, aryl containing from 6 to 10 carbon atoms carbon or aralkyl group containing from 7 to 11 carbon atoms, optionally being substituted nucleus of aryl or aralkyl radical with OH, NH2, NO2 radical, alkyl containing 1 to 6 carbon atoms, alkoxy containing 1 to 6 carbon atoms or with one or more halogen atoms, R6 and R7, identical or different, are selected from the group consisting of a hydrogen atom, an alkyl radical comprising from 1 to 6 carbon atoms, aryl containing from 6 to 10 carbon atoms and aralkyl containing from 7 to 11 at omos carbon, optionally substituted by a carbamoyl radical, ureido or dimethylamino, and an alkyl radical comprising from 1 to 6 carbon atoms substituted by a pyridyl radical, n 'is equal to 1 or 2 R5 is selected from the group consisting of a COOH radical, CN, OH, NH2, CO-NR6R7, COOR, oR, OCHO, OCOR, OCOOR, OCONHR, OCONH2, NHR, NHCOH, NHCOR, NHSO2R, NH-COOR, NH-CO-NHR or NHCONH2, being defined R 6 and R 7 above; R2 represents a hydrogen atom or a group (CH2) n'1R5, n'1 being equal to 0, 1 or 2 and R5 being defined as above; R3 represents a hydrogen atom or an alkyl radical comprising from 1 to 6 carbon atoms; A represents a bond between the two carbon atoms bearing R1 and R2 or a group, R4 representing a hydrogen atom or a group (CH2) n'1R5, n'1 and R5 being defined as above, and representing the line an optional bond points complementary to any one of the carbon atoms bearing the substituents R1 and R2, n is 1 or 2, X represents a divalent group -C (O) -B- linked to the nitrogen atom by atom carbon, B represents a divalent group -O- (CH2) n '' - group attached to the carbonyl oxygen atom by a group -NR8- (CH2) n '' - or -NR8-O- group attached to the carbonyl by the nitrogen atom, n 'is equal to 0 or 1 and R8, in the case of -NR8- (CH2) n' '- is selected from the group consisting of a hydrogen atom, an OH, R radical, OR, Y, OY, Y1, OY1, Y2, OY2, Y3, OCH2CH2SOmR, OSiRaRbRc and SiRaRbRc, and in the case of -NR8-O- is chosen from the group consisting of a hydrogen atom, a radical R, Y, Y1, Y2, Y3 and SiRaRbRc, individually representing Ra, Rb and Rc a linear or branched alkyl comprising 1 to 6 carbon atoms or an aryl radical comprising from 6 to 10 carbon atoms, and being defined R as above and m being equal to 0, 1 or 2, NX (CH) n 2 ES 2356813 T3 C R1 R3 NR 6 a NHR 7 R2 C (H) R 4 Y is selected from the group consisting of the COH, COR, COOR, CONH2, CONHR, CONHOH radicals , CONHSO2R, CH2COOH, CH 2 COOR, CH2CONHOH, CH2CONHCN, CH2tétrazol protected CH2tétrazol, CH2SO3H, CH2SO2R, CH2PO (OR) 2, CH2PO (OR) (OH), CH2PO (R) (OH) and CH2PO (OH) 2, Y1 selected from the group consisting of the SO2R, SO2NHCOH, SO2NHCOR, SO2NHCOOR, SO2NHCONHR, SO2NHCONH2 and SO3H radicals, Y2 is chosen from the group consisting of radicals PO (OH) 2, PO (OR) 2, PO (OH) and PO (OH) (R), Y3 is selected from the group consisting of the tetrazole radicals, tetrazole substituted by the R radical, squarate, NH or NR-tetrazole, NH or NR tetrazole substituted by the R radical, NHSO2R and NRSO2R , stand or R defined above; it being understood that when n is equal to 1 and A represents a group wherein R4 is a hydrogen atom and - either X represents -O- -C (O) (CH2) n '' wherein n ' 'is 0 or 1, - or X represents the -CO-NR 8 group (CH2) n' 'wherein n' 'is 1 and R8 is the isopropyl group, - or X represents the group -CO-NR8 - (CH2) n '' wherein n '' is 0 and R8 is hydrogen or phenyl, then R1, R2 and R3 may not represent three simultaneously a hydrogen atom, and pharmaceutically acceptable salts thereof, in the preparation of a medicament for inhibiting the production of - lactamases by pathogenic and characterized bacteria that the compound of formula (I) is associated with a type antibiotic -lactamine, in the preparation of said medicament intended for simultaneous, separate or sequential in time of the active ingredients in antibacterial therapy.