Design, synthesis and biological evaluation of novel azaspiro analogs of linezolid as antibacterial and antitubercular agents

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

doi:10.1016/j.ejmech.2016.07.001

Cited by 36 publications

(21 citation statements)

References 19 publications

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“…5 Thus, spirodiamine cores, most notably arylspiroalkanes (Figure 1), are present in many biologically active compounds 6 with reported antipsychotic, 7 anti-insomnia, 8 age-related macular degeneration (AMD), 9 and anti-viral 10 properties, among others. 1d, 9, 11…”

Section: Introductionmentioning

confidence: 99%

Pd-catalyzed arylation of linear and angular spirodiamine salts under aerobic conditions

Reilly

Bryan

Mach

2017

Tetrahedron Letters

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Application of Buchwald-Hartwig catalysis for development of biologically relevant arylspirodiamine compounds is reported. This synthetic methodology requires no inert atmosphere and affords yields up to 93% in just 20 min. Linear and sterically hindered angular spirodiamines in salt and free-base form are coupled with electron-rich and -withdrawing aryl chlorides, demonstrating a broad scope and applicability of this protocol.

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Section: Introductionmentioning

confidence: 99%

Pd-catalyzed arylation of linear and angular spirodiamine salts under aerobic conditions

Reilly

Bryan

Mach

2017

Tetrahedron Letters

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“…The most conventional 2‐oxazolidinones synthesis is carried out by cyclizing amino alcohols with phosgene, followed by C−N coupling (Scheme A) . These steps may also be executed in reverse order . A less common approach involves reacting the corresponding isocyanate with an electrophilic alcohol, which is then cyclized (Scheme B) .…”

Section: Methodsmentioning

confidence: 99%

One‐Step Synthesis of 3,4‐Disubstituted 2‐Oxazolidinones by Base‐Catalyzed CO₂ Fixation and Aza‐Michael Addition

Mannisto

Sahari

Lagerblom

et al. 2019

Chemistry A European J

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2-Oxazolidinones are saturated heterocyclic compounds, which are highly attractive targets in modern drug design. Herein, we describe an ew,s ingle-step approach to 3,4-disubstituted 2-oxazolidinones by aza-Michael addition using CO 2 as ac arbonyl source and 1,1,3,3tetramethylguanidine (TMG) as ac atalyst. The modular reaction, whicho ccurs between a g-brominated Michael acceptor,C O 2 and an arylamine, aliphatic amine or phenylhydrazine, is performedu nder mild conditions. The regiospecific reaction displays good yields (av.7 5%)a nd excellent functional-group compatibility. In addition, late-stage functionalization of drug and drug-like molecules is demonstrated. The experimental results suggest am echanism consisting of severale lementary steps:T MG-assistedc arboxylation of aniline;g eneration of an O-alkyl carbamate; and the final ring-forming step through an intramolecular aza-Michaela ddition.

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“…The activity evaluation results indicated that Compound 36 (MIC = 2.55 μg/ml), which had a similar structure with compound 34 (linezolide), still preserved some activity of Compound 34 (MIC = 1.31 μg/ml). The cytotoxic activity (IC 50 ) of Compound 35 against M. tuberculosis H37Ra, E. coli , Pseudomonas aeruginosa , S. aureus , and Bacillus subtilis was 1.56, >100, 0.58, 0.53, and 0.49 μg/ml, respectively (Gadekar et al, ).…”

Section: Five‐membered Ring Compoundsmentioning

confidence: 99%

Opportunities and challenges of using five‐membered ring compounds as promising antitubercular agents

Wang

et al. 2020

Drug Development Research

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Tuberculosis (TB), a chronic infectious disease, is one of the greatest risks to human beings and 10 million people were diagnosed with TB and 1.6 million died from this disease in 2017. In addition, with the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the TB situation has become even worse, which has aggravated the mortality and spread of this disease.To overcome this problem, research into novel antituberculosis agents with enhanced activities against MDR-TB, reduced toxicity, and shortened duration of therapy is of great importance. Fortunately, many novel potential anti-TB drug candidates with five-membered rings, which are most likely to be effective against sensitive and resistant strains, have recently entered clinical trials. Different five-membered rings such as furans, pyranoses, thiazoles, pyrazolines, imidazoles, oxazolidinone, thiazolidins, isoxazoles, triazoles, oxadiazoles, thiadiazoles, and tetrazoles have been designed, prepared, and evaluated for their antimycobacterial activity against Mycobacterium tuberculosis. In this article, we highlight the recent advances made in the discovery of novel five-membered ring compounds and focus on their antitubercular activities, toxicity, structure-activity relationships, and mechanisms of action. K E Y W O R D Santi-TB drug, antitubercular activities, five-membered ring, MDR-TB, tuberculosis

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Design, synthesis and biological evaluation of novel azaspiro analogs of linezolid as antibacterial and antitubercular agents

Cited by 36 publications

References 19 publications

Pd-catalyzed arylation of linear and angular spirodiamine salts under aerobic conditions

Pd-catalyzed arylation of linear and angular spirodiamine salts under aerobic conditions

One‐Step Synthesis of 3,4‐Disubstituted 2‐Oxazolidinones by Base‐Catalyzed CO₂ Fixation and Aza‐Michael Addition

Opportunities and challenges of using five‐membered ring compounds as promising antitubercular agents

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Design, synthesis and biological evaluation of novel azaspiro analogs of linezolid as antibacterial and antitubercular agents

Cited by 36 publications

References 19 publications

Pd-catalyzed arylation of linear and angular spirodiamine salts under aerobic conditions

Pd-catalyzed arylation of linear and angular spirodiamine salts under aerobic conditions

One‐Step Synthesis of 3,4‐Disubstituted 2‐Oxazolidinones by Base‐Catalyzed CO2 Fixation and Aza‐Michael Addition

Opportunities and challenges of using five‐membered ring compounds as promising antitubercular agents

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Product

Resources

About

One‐Step Synthesis of 3,4‐Disubstituted 2‐Oxazolidinones by Base‐Catalyzed CO₂ Fixation and Aza‐Michael Addition