Synthesis and Antitubercular Activity of Piperidine and Morpholine 1, 8 Naphthyridine Analogues

Abstract

Objective: The search for new, potentially useful antimycobacterial agents. In continuation with our previous screening for the discovery of novel drugs for tuberculosis, a new series of 1,8-naphthyridines derivatives were synthesized and evaluated in vitro for antimycobacterial activity against Mycobacterium tuberculosis H37Rv.Methods: Several 4-morpholinomethyl-1.8-naphthyridine derivatives have been synthesized in excellent yields. The synthesized compounds were characterized by spectroscopic methods as well as elemental analyses. They were screened for their antimycobacterial activity. The growth was monitored radiometrically in 7H12 broth with the BACTEC 460 TB system. The minimum inhibitory concentration (MIC) was determined for compounds that demonstrated ≥ 90% growth inhibition in the primary screening. Results:The obtained data suggested that all compounds showed significant activity against Mycobacterium tuberculosis H37Rv compared to the standard reference drug. Analogues (6-11) having heterocyclic groups in position 7 were the most potent of those we tested. Conclusion:These findings clearly identify the 1,8-naphthyridine analogue (10) with a 6-amino-2-(4'-methoxy benzylamine-4-morpholinomethyl-7-morpholino-substituent as promising anti-tubercular agents possessing significant activity against Mycobacterium tuberculosis H37Rv

Design, Synthesis and Biological Evaluation of Novel Spiro‐[Chroman‐2,4′‐Piperidin]‐4‐One Analogs as Anti‐Tubercular Agents

“…In continuation to our ongoing research on finding novel anti‐tubercular agents [32–36] as well as the importance of spiro‐[chroman‐2,4′‐piperidin]‐4‐one derivatives, the present work was planned. In the design strategy, based on the literature reports, we anticipated that the derivatization of the spirochromanone scaffold at its seventh position with novel phenyl analogs may lead to potent anti‐tubercular candidates [37–39] . As a result, we present our initial findings on the synthesis and biological evaluation of spirochromanones as anti‐tuberculosis agents in the current work.…”

Synthesis and Antibacterial Activity of Novel 5-Arylidene-2-Imino-3-(2- Phenyl- 1,8-Naphthyridin-3-Yl)thiazolidin-4-Ones

“…Among the different classes of heterocyclic units, the 1,8-naphthyridine unit is a privileged scaffold and widely distributed in many biologically active synthetic compounds [2]. 1,8-naphthyridine and its derivatives possess valuable pharmacological applications including antibacterial [3], antidepressant [4], antitubercular [5], anticancer [6], antihypertensive [7], and antiplatelet [8] activities. Similarly, thiazolidin-4-one and its 5-arylidene derivatives are represented as an interesting class of molecules showing a broad-spectrum of medical applications such as antimicrobial [9], anti-inflammatory [10], DPPH radical scavenger [11], antifungal [12], anticancer [13], and anticonvulsant [14] activities.…”