G. Aridoss

A facile synthesis, antibacterial, and antitubercular studies of some piperidin-4-one and tetrahydropyridine derivatives.

The raise in clinical significance of multidrug-resistant bacterial pathogens has directed us to synthesize 2,6-diarylpiperidin-4-one and Delta(3)-tetrahydropyridin-4-ol based benzimidazole and O-arylsulfonyl derivatives. X-ray crystal structure of tetrahydropyridinol (23) confirmed a change in conformation and orientation of substituents upon amide formation. Antibacterial activities evaluated against a wide number of bacterial pathogens (both sensitive and multidrug-resistant) revealed that 19, 27 against Staphylococcus aureus, 27 against Enterococcus faecalis, and 19, 21, 23, and 27 against Enterococcus faecium are significantly good at lowest MIC(90) (16 microg/mL). Inhibitory power noticed by 23 against Vancomycin-Linezolid-resistant E. faecalis and 27 against Vancomycin-resistant E. faecium are onefold better than the standard Linezolid and Trovafloxacin drugs, respectively. Moreover, antitubercular activity for the selected compounds against Mycobacterium tuberculosis H37Rv revealed that compounds 23, 24, and 27 expressed onefold improved potency compared to the standard Rifampicin drug.

Synthesis, spectral and biological evaluation of some new thiazolidinones and thiazoles based on t-3-alkyl-r-2,c-6-diarylpiperidin-4-ones.

A stereospecific synthesis of some thiazolidinones and thiazoles was achieved conveniently through certain alpha-halo keto agents and reactivity of chloroacetyl chloride was successfully enhanced by CsF-Celite+CH(3)COONa. NMR studies revealed that the configuration of N-N bond is found to be anti with respect to C-3 alkyl group while C=N bond in thiazolidinone is trans with respect to N-N bond. Antimycobacterial activity tested against Mycobacterium tuberculosis indicated that compounds 19, 20, 24, 29, 30 and 32 exhibited twofold enhanced potency than Rifampicin. Similarly, antimicrobial screening studies pointed out that compounds 21 and 28 exceptionally noticed promising activities and particularly, 21 against Staphylococcus aureus and, 24 and 32 against Rhizopus sp. exhibited onefold elevated inhibition potency whereas 21 against Klebsiella pneumoniae showed twofold improved potency than Ciprofloxacin and Amphotericin B.

Synthesis, spectral, crystal and antimicrobial studies of biologically potent oxime ethers of nitrogen, oxygen and sulfur heterocycles.

Three series of oxime ethers viz, 2,6-diarylpiperidin-4-one O-benzyloximes 5a-o, 2,6-diaryltetrahydropyran-4-one O-benzyloximes 7a-e and 2,6-diaryltetrahydrothiopyran-4-one O-benzyloximes 11a-b and 12a-c were synthesized and stereochemistry is established by their spectral and single crystal analysis. A SAR study has been carried out for the above oxime ethers against a panel of antibacterial (Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhi and Escherichia coli) and antifungal agents (Candida albicans, Candida-51, Rhizopus sp., Aspergillus niger, Aspergillus flavus and Cryptococcus neoformans), respectively, using Ciprofloxacin and Amphotericin B as standards. Most of the chloro/methyl/methoxy substituted compounds exerted moderate to good activity against all the tested organisms; moreover, some compounds (5i, 5l, 5n, 5o, 7c2, 7d1, 7d2, 7e, 11b and 12c) exhibited promising activity than standard drugs.

Synthesis and spectral characterization of a new class of N-(N-methylpiperazinoacetyl)-2,6-diarylpiperidin-4-ones: Antimicrobial, analgesic and antipyretic studies

A series of N-(N-methylpiperazinoacetyl)-2,6-diarylpiperidin-4-ones (13c-21c) were synthesized by the base catalyzed nucleophilic substitution of N-chloroacetyl-2,6-diarylpiperidin-4-ones obtained from their corresponding 2,6-diarylpiperidin-4-ones with N-methylpiperazine. These newly synthesized compounds were characterized by one- and two-dimensional NMR spectral studies. In all the cases, the piperazine ring adopted normal chair conformation with equatorial orientation of methyl group irrespective of the non-chair conformations of the piperidin-4-one moiety. All the compounds were screened for their possible antibacterial and antifungal activities against a spectrum of microbial agents besides analgesic and antipyretic activities. These biological studies proved that compounds 17c/18c against bacterial and 18c/20c against fungal strains exhibited promising antimicrobial activities whereas 17c/19c and 18c/19c showed beneficial analgesic and antipyretic profiles, respectively, at a concentration of 60mg/kg and were also found to be more potent than the reference drug.

Synthesis, stereochemistry and antimicrobial studies of novel oxime ethers of aza/diazabicycles

Two series of bicyclic oxime ethers viz, 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one O-benzyloximes 13-24 and 2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1]nonan-9-one O-benzyloximes 31-36 were synthesized and stereochemistry was established by their spectral (1D and 2D NMR) and crystal studies. Synthesized oxime ethers were screened for their in vitro antimicrobial activity against a set of pathogenic bacteria (Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhi, Escherichia coli and Klebsiella pneumoniae) and fungi (Candida albicans, Candida-51, Rhizopus sp., Aspergillus niger and Aspergillus flavus) by twofold serial dilution method, respectively, using Ciprofloxacin and Amphotericin B as standards. Most of the molecules expressed promising antimicrobial profile against the tested pathogens and even a few compounds 16, 21, 22, 33 and 34 were better than standard drugs.

Synthesis and Microbiological Evaluation of Some N-Methyl Piperidone Oxime Ethers

Some variously substituted 1-methyl-2,6-diarylpiperidin-4-one O-benzyloximes have been synthesized and their antibacterial activity against Pseudomonas aeruginosa, Salmonella typhi, Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae and antifungal activity against Candida albicans, Cryptococcus neoformans, Rhizopus sp, Aspergillus niger and Aspergillus flavus were evaluvated. Compounds 26 and 30 exhibited potent in vitro antibacterial activity against Salmonella typhi, Escherichia coli and Klebsiella pneumoniae. While compound 28 proved to be potent against Salmonella typhi and Klebsiella pneumoniae. Like wise, compounds 26 and 28 exerted potent in vitro antifungal activity against Cryptococcus neoformans, Aspergillus niger and Aspergillus flavus whereas 30 showed very good activity than the standard drug against all the tested organisms.

Synthesis, crystal and antibacterial studies of diversely functionalized tetrahydropyridin-4-ol.

In an effort to expand the spectrum of antibacterial activity associated with piperidin-4-one derivatives, we have synthesized two series of 3-carboxyethyl-2,6-diphenyl-4-hydroxy-Delta(3)-tetrahydropyridine derivatives bearing diversified heterocyclic and aromatic systems at the nitrogen atom through acetyl (6-18) and 2-propanoyl (9-31) linkers. Unlike acetyl derivatives, NMR spectral pattern of the propanoyl counterparts revealed the existence of pair of rotational isomers (syn and anti) in solution at room temperature due to the hindered rotation about N-CO bond. X-ray crystal studies of 9 and 24 clearly pointed out that all the compounds existed in only one form particularly, in stable syn form in solid state. Each of the compounds was screened for their in vitro antibacterial activity against nine human pathogenic gram-positive strains including multiple drug resistant organisms and seven problematic gram-negative strains. Among the various heterocycles examined here, imidazole substituted derivatives 12 and 25 exhibited antibacterial activity approaching that of Linezolid and Trovafloxacin drugs particularly against multiple resistant Enterococcus faecium-VanA phenotype strains.

Synthesis and antimicrobial activities of N-chloroacetyl-2,6-diarylpiperidin-4-ones

An array of new N-chloroacetyl-2,6-diarylpiperidin-4-ones has been synthesised and their antibacterial activity against Staphylococcus aureus, Escherichiacoli, Bacillussubtilis, Pseudomonas aeruginosa, and Salmonella typhi, and antifungal activity against Cryptococcusneoformans, Candida albicans, Rhizopus sp., Aspergillus flavus, and Aspergillus niger examined. Compounds 14 against P. aeruginosa, 15 against S. typhi, 16 against S. aureus, and 19 against B. subtilis showed marked antibacterial activity. Similarly, compounds 15 and 19 against A. niger and 19 against A. flavus exerted significant antifungal activities.

1H and 13C NMR spectral assignments of some novel 2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1]nonan-9-one derivatives

The 1H and 13C NMR spectra of 2,4,6,8‐tetraaryl‐3,7‐diazabicyclo[3.3.1]nonan‐9‐ones (1–2), oximes (3–8) and O‐benzyl oximes (9–12) were recorded. The chemical shifts were unambiguously assigned using 1D and 2D NMR spectral data. The results clearly indicate that the compounds exist in chair‐boat conformation with equatorial and axial orientation of the aryl groups in the chair and boat forms, respectively. Since the molecules are flexible and dynamic in solution, the chair and boat forms are mutually interconvertible. In 3–12, because of the effect of oximation/oximination, all the protons in the heterobicyclic systems gave distinct signals except the benzylic protons of the boat form. In all synthesized compounds, the aryl group protons at C‐6,8 are shielded by the aryl groups at C‐2,4 and therefore appear in the lower frequency region than the aryl groups at C‐2,4. Copyright

r-2,c-6-Bis(4-fluoro-phen-yl)-t-3,t-5-dimethyl-piperidin-4-one.

In the title compound, C19H19F2NO, the piperidinone ring adopts a chair conformation. The crystal packing is stabilized by C—H⋯O and C—H⋯F intermolecular interactions, generating centrosymmetric dimers of R 2 2(14) and R 2 2(24) rings.