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

Abstract

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, ¹H and ¹³C-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.

Keywords:

• Oxazolidinone
• amides
• sulfonamide
• thienopyridine
• antibacterial agent

Acknowledgements

Authors thank General Secretary and authorities, MVP Samaj Nashik, Dr. A. D. Bholay Post Graduate Department of Microbiology, KTHM College, Nashik for antimicrobial assay evaluation, Principal KTHM College, Nashik and Savitribai Phule Pune University, Pune.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Table 1. Some physicochemical and analytical data of the compounds bearing thieno-pyridin.

Table 2. The zone of inhibition in mm of synthesized compound (11a–n).