Nitrogenous heterocyclic compounds, preparation thereof and use thereof as antibacterial medicaments

A compound selected from the following group:

• trans 8-(aminomethyl)-4,8-dihydro-1-methyl-6-oxo-5(sulphooxy)-4,7-methano-7H-pyrazolo[3,4-e][1,3]diazepin-6(5H)-one;
• trans 8-(aminomethyl)-4,8-dihydro-6-oxo-5-(sulphooxy)-4,7-methano-7H-pyrazolo[3,4-e][1,3]diazepin-6(5H)-one;
• and
• trans 8-(methylaminomethyl)-4,8-dihydro-6-oxo-5-(sulphooxy)-4,7-methano-7H-pyrazolo[3,4-e][1,3]diazepin-6(5H)-one;
• or a pharmaceutically acceptable salt or zwitterion thereof.

A method for preparing a compound of formula (I), comprising the steps of:

• a) reacting a compound of formula (II) with a carbonylating agent, if necessary in the presence of a base:
• wherein:
• R′1, represents a CN, protected COOH, COOR or (CH2)nR′5 radical;
• R′5 is a protected OH, CN, NH2 or protected NHR, protected CO2H, CO2R radical;
• R is a (C1-C6)alkyl;
• n is equal to 1 or 2;
• R3 and R4 together form an aromatic nitrogenated heterocycle with 5 apexes with 1, 2 or 3 nitrogen atoms optionally substituted by one or several R′ groups, R′ being selected from the group consisting of a hydrogen atom and alkyl radicals with 1 to 6 carbon atoms;
• wherein the aminoalkyl substituents optionally present on the heterocycle formed by R3 and R4 being protected if necessary;
• ZH represents a protected —NHOH group;
• thereby forming an intermediate compound with the formula (III):
• wherein:
• either X1 is a hydrogen atom or a protecting group and X2 represents a —Z—CO—X3 group, wherein X3 represents the rest of the carbonylating agent, or
• X2 is a —ZH group and X1 represents a CO—X3 group, wherein X3 represents the rest of the carbonylating agent;
• b) cyclising the intermediate compound represented by formula (III) in the presence of a base;
• and
• c) completing, if necessary, one or several of the following reactions:
• protection of the reactive functions,
• deprotection of the reactive functions,
• esterification
• saponification,
• sulphatation,
• ester reduction,
• alkylation,
• carbamoylation,
• formation of an azido group,
• reduction of an azido into an amine,
• salification,
• ion exchange,
• dividing or separating the diastereoisomers;
• either before step a) or after step b), or both, thereby forming the compound represented by formula (I).