Synthesis and Evaluation of Novel (5S)-5-(Aminomethyl)-3-[4-(6,7-Dihydrothieno[3,2-c]Pyridin-5(4H)-yl)Phenyl]-1,3-Oxazolidin-2-One Derivatives as Potent Antimicrobial Agents

• Published in: Polycyclic aromatic compounds 2023-08, Vol.43 (7), p.6470-6483
• Main Authors: Patekar, Mukunda, Mali, Anil, Kalawade, Kaustubh, Jadhav, Ghanshyam, Deshmukh, Dattatray, Medhane, Vijay
• Format: Article
• Language: English
• Subjects: Acetyl chloride; Amides; Antibacterial activity; antibacterial agent; Antimicrobial agents; Aqueous solutions; Bacteria; Carbonyl compounds; Carbonyls; Carboxylic acids; Diketones; Dimethylformamide; Gram-positive bacteria; Hydrazine; Hydrazines; Imidazole; Isopropanol; Isopropyl alcohol; Methane; Nickel; Nitro compounds; Nitrobenzene; NMR; Nuclear magnetic resonance; Oxazolidinone; Room temperature; Substitution reactions; sulfonamide; Sulfonamides; Synthesis; thienopyridine; Toluene
• ISSN: 1040-6638; 1563-5333
• DOI: 10.1080/10406638.2022.2118324

In the present work, a series of novel oxazolidinone derivatives containing thieno-pyridine ring system (11a-n) were synthesized in six steps. Synthesis of amino oxazolidinone scaffold (10) involved nucleophilic substitution of thienopyridine (4) with P-chloro-nitrobenzene (3) in dimethyl formamide at 65 °C give nitro compound (5) which was further reduced in catalytic hydrogenation condition using Raney-Nickel in isopropyl alcohol afforded amine (6). Reaction of compound (6) with 2-[(2S)-oxiran-2-ylmethyl]-1H-isoindole-1,3(2H)-dione (7) at mild reflux condition in isopropyl alcohol gives compound (8). Hydroxy amine compound (8) further undergo carbonyl insertion reaction with 1, 1'-carbonylbis(1H-imidazole) afforded oxazolidinone compound (9). The de-protection of phthalamide group of compound (9) carried by treating with aqueous solution of hydrazine hydrate in methanol at room temperature give compound (10). Finally, compound (10) reacts with acetyl chloride, carboxylic acid, sulfonyl chloride and chloro format by customary method provided amides, sulfonamide and carbamate derivative of (5S)-5-(aminomethyl)-3-[4-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)phenyl]-1,3-oxazolidin-2-one. The developed synthetic approach was operationally simple and high yielding. The structures of the synthesized compounds were elucidated by IR, MS, 1 H and 13 C-NMR. Synthesized compounds (11a-n) were tested for antibacterial activity against a panel of Gram-positive bacteria comprising Staphylococcus aureus (ATCC5638), Streptococcus pyogenes (ATCC12344), Bacillus subtilis (ATCC6051), Bacillus pumilus (ATCC27142), and Enterococcus faecalis (NCIM5253). The investigation of antimicrobial screening data revealed that, most of the compounds tested have demonstrated sensible to good bacterial activity. In summary, preliminary results of activity indicate that, acetyl derivative (11a), methane sulfonamide derivative (11c) and p-toluene sulfonamide derivative (11e) found to be good activity and di-(methane sulfonamide) derivative (11d) showed comparable activity to reference drug substances.