ABSTRACT
A few thienyl substituted pyrazole derivatives were synthesized to aid in the characterization of the cannabinoid receptor antagonist and also to serve as potentially useful antiobesity agent. Structural requirements for selective CB1 receptor antagonistic activity of 5-thienyl pyrazole derivatives included the structural similarity with potent, specific antagonist rimonabant 1. Compound 3 has been identified as a hair growth stimulator and an antiobesity agent in animal models.
Subject(s)
Chemistry, Pharmaceutical/methods , Hair/drug effects , Obesity/drug therapy , Piperidines/chemical synthesis , Pyrazoles/chemical synthesis , Receptor, Cannabinoid, CB1/antagonists & inhibitors , Animals , Benzoxazines/pharmacology , CHO Cells , Cricetinae , Cricetulus , Cyclic AMP/metabolism , Drug Design , Inhibitory Concentration 50 , Models, Chemical , Morpholines/pharmacology , Naphthalenes/pharmacology , Piperidines/pharmacology , Pyrazoles/pharmacology , RimonabantABSTRACT
Design and synthesis of novel piperazinylaryloxazolidinones possessing heteroaryl groups are described and their in vitro antibacterial activities have been evaluated by MIC assay. Compounds (S)-N-[3-{3-fluoro-4-[4-[3-(5-nitrofuran-2-yl)-acryloyl]-piperazin-1-yl]-phenyl}-2-oxo-oxazolidin-5-yl-methyl] acetamide (6o), (S)-N-[3-{3-fluoro-4-[4-[3-(5-nitrothien-2-yl)-acryloyl]-piperazin-1-yl]-phenyl}-2-oxo-oxazolidin-5-yl-methyl] acetamide (6p) and N-oxide of (S)-N-[3-{3-fluoro-4-[4-[3-(5-nitrofuran-2-yl)-acryloyl]-piperazin-1-yl]-phenyl}-2-oxo-oxazolidin-5-yl-methyl] acetamide (9) showed superior antibacterial activities than linezolid and also active against the linezolid resistant Staphylococcus aureus strains.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Oxazolidinones/chemical synthesis , Oxazolidinones/pharmacology , Staphylococcus aureus/drug effects , Acetamides/pharmacology , Anti-Bacterial Agents/chemistry , Drug Design , Linezolid , Microbial Sensitivity Tests , Molecular Structure , Oxazolidinones/chemistry , Structure-Activity RelationshipABSTRACT
Design and synthesis of a few novel methylamino piperidinyl substituted oxazolidinones are reported. Their antibacterial activities have been evaluated in a MIC assay against broader panel of both susceptible and resistant Gram-positive strains. (S)-N-{3-[3-Fluoro-4-(methyl-{1-[3-(5-nitrofuran-2-yl)-acryloyl]-piperidin-4-yl}-amino)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide 4i has shown comparable antibacterial activity to linezolid and eperezolid in the MIC assay, additionally compound 4i showed good antibacterial activity with an in vitro MIC value of 2-4 microg/mL against linezolid resistant Staphylococcus aureus (linezolid 16 microg/mL).
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Oxazolidinones/chemical synthesis , Oxazolidinones/pharmacology , Piperidines/chemistry , Anti-Bacterial Agents/chemistry , Microbial Sensitivity Tests , Oxazolidinones/chemistryABSTRACT
A few substituted piperazinylphenyloxazolidinone compounds 6-13 having substitution on the distant nitrogen atom of piperazine ring scaffold have been synthesized and evaluated for their antibacterial activity in Gram-positive bacteria. A few compounds showed superior in vitro antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, and Streptococcus pyogenes than linezolid and eperezolid.
Subject(s)
Anti-Bacterial Agents , Gram-Positive Bacteria/drug effects , Oxazolidinones , Piperazines/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Enterococcus faecalis/drug effects , Enterococcus faecalis/growth & development , Gram-Positive Bacteria/growth & development , Microbial Sensitivity Tests , Oxazolidinones/chemical synthesis , Oxazolidinones/chemistry , Oxazolidinones/pharmacology , Piperazine , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development , Staphylococcus epidermidis/drug effects , Staphylococcus epidermidis/growth & development , Streptococcus pyogenes/drug effects , Streptococcus pyogenes/growth & developmentABSTRACT
A few Mannich ketones of piperazinyl oxazolidinone derivatives have been synthesized and their antibacterial activity in various Gram-positive organisms such as Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis were evaluated by MIC determination. Compound 12 showed comparable activity (MIC) to linezolid and superior to eperezolid.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Ketones/chemical synthesis , Oxazolidinones/chemical synthesis , Piperazines/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacillus subtilis/drug effects , Enterococcus faecalis/drug effects , Ketones/chemistry , Ketones/pharmacology , Microbial Sensitivity Tests , Oxazolidinones/chemistry , Oxazolidinones/pharmacology , Piperazines/chemistry , Piperazines/pharmacology , Staphylococcus aureus/drug effects , Staphylococcus epidermidis/drug effectsABSTRACT
Synthesis of a number of 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine substituted oxazolidinones have been reported. They have been screened against a panel of Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. A SAR has been developed. Compound 15 showed comparable activity (MIC) to linezolid and superior to eperezolid.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Enterococcus faecalis/drug effects , Oxazoles/chemical synthesis , Pyridines/chemical synthesis , Staphylococcus aureus/drug effects , Acetamides/pharmacology , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial , Linezolid , Methicillin/pharmacology , Microbial Sensitivity Tests , Oxazoles/pharmacology , Oxazolidinones/chemistry , Oxazolidinones/pharmacology , Pyridines/pharmacology , Structure-Activity Relationship , Vancomycin/pharmacologyABSTRACT
A number of substituted piperazinyl oxazolidinone derivatives have been synthesized and their antibacterial activities were evaluated by MIC determination. A systematic SAR was carried out to get highly potent oxazolidinone derivatives.