Methods of generating beta-lactamase resistant carbapenem compounds
The present invention includes compositions, methods of making and using novel carbapenem compounds including active agents, compounds, antibacterial agents, pharmaceutically acceptable salts of C1α-C1β di-substituted carbapenem compounds, C5α substituted carbapenem compounds, C6α-C6β di-substituted carbapenem compounds and combinations thereof.
1. A composition comprising a carbapenem compound having the formula:
or enantiomers or diastereoisomers thereof,
wherein R1 and R1′ are independently selected from —H, —CH 2 CH 2 OH, —CHOHCH 3 , —CH 2 NHR*, —CH 2 OCONHR* and —CO 2 H;
wherein R5 is selected from —CH 2 NHR*, —CH 2 OCONHR* and —CH 2 COCONHR*;
wherein R6 and R6′ are independently selected from —H and —CHOHCH 3 ;
wherein R* is hydrogen; and
wherein R2 is
{2-[(iminomethyl)amino]ethyl}
[5-(dimethylcarbamoyl) pyrrolidin-2-yl]
or
[(3S)-1-ethanimidoylpyrrolidin-3-yl]
2. An antibacterial composition comprising
a carbapenem compound or its pharmaceutically acceptable salt as an active ingredient having the formula:
or enantiomers or diastereoisomers thereof,
wherein R1 and R1′ are independently selected from —H, —CH 2 CH 2 OH, —CHOHCH 3 , —CH 2 NHR*, —CH 2 OCONHR* and —CO 2 H;
wherein R5 is selected from —CH 2 NHR*, —CH 2 OCONHR* and —CH 2 COCONHR*;
wherein R6 and R6′ are independently selected from —H and —CHOHCH 3 ;
wherein R* is hydrogen; and
wherein R2 is
{2-[(iminomethyl)amino]ethyl}
or
[5-(dimethylcarbamoyl) pyrrolidin-2-yl]
and a pharmaceutically acceptable carrier, excipient, binder or stabilizer.