0

Design, Synthesis and Biological Evaluation of Novel Azaspiro Analogs of Linezolid as Antibacterial and Antitubercular Agents

Pradip K Gadekar, Abhijit Roychowdhury, Prashant S Kharkar, Vijay M Khedkar, Manisha Arkile, Hardik Manek, Dhiman Sarkar, Rajiv Sharma, V Vijayakumar, S Sarveswari

Eur J Med Chem. 2016 Oct 21;122:475-487.

PMID: 27423637

Abstract:

The design, synthesis and antimicrobial evaluation of a novel series of azaspiro analogues of linezolid (1) have been described. Linezolid comprises of a morpholine ring which is known for its metabolism-related liabilities. Therefore, the key modification made in the linezolid structure was the replacement of morpholine moiety with its bioisostere, 2-oxa-6-azaspiro[3.3]heptane. Furthermore, the replacement of N-acetyl terminal of 1 with various aromatic or aliphatic functionalities was carried out. The title compounds were evaluated against a panel of Gram-positive and Gram-negative bacteria and Mycobacterium tuberculosis. Subsequent structure-activity relationship (SAR) studies identified several compounds with mixed antibacterial and antitubercular profiles. Compound 22 (IC50 0.72, 0.51, 0.88, 0.49 μg/mL for Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, respectively) exhibited similar antibacterial profile as 1. The N-acetyl derivative 18 was similar to 1 in antitubercular profile. Thus, the present study successfully demonstrated the use of azaspiro substructure in the medicinal chemistry of antibacterial and antitubercular agents.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP168828840 Linezolid Related Compound A Linezolid Related Compound A 168828-84-0 Price
qrcode