N/C-4 substituted azetidin-2-ones: Synthesis and preliminary evaluation as new class of antimicrobial agents

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 2, 2007, Pages 341-345

  Halve, Anand K ^a   Bhadauria, Deepti ^a   dubey, Rakesh ^a  

^a JIWAJI UNIVERSITY   (India)

Author keywords

Azetidin 2 ones; B. anthracis; C. albicans; Pharmacophore; SAR

Indexed keywords

ANTIINFECTIVE AGENT; AZETIDINONE DERIVATIVE; CHLORAMPHENICOL;

ANTIMICROBIAL ACTIVITY; ARTICLE; BACILLUS ANTHRACIS; CANDIDA ALBICANS; CONTROLLED STUDY; DRUG POTENCY; DRUG SCREENING; DRUG STRUCTURE; NONHUMAN; STAPHYLOCOCCUS AUREUS; STRUCTURE ACTIVITY RELATION;

ANTI-BACTERIAL AGENTS; ANTI-INFECTIVE AGENTS; ANTIFUNGAL AGENTS; AZETIDINES; BACTERIA; CYCLIZATION; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; FUNGI; INDICATORS AND REAGENTS; MICROBIAL SENSITIVITY TESTS; STRUCTURE-ACTIVITY RELATIONSHIP;

BACILLUS ANTHRACIS; CANDIDA ALBICANS;

EID: 33846036891     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.10.064     Document Type: Article

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31. General procedure for the synthesis of 2-hydroxy-5-(nitro substituted phenylazo) benzylidene anilines (5a-h): An equimolar mixture (0.005 M) of compound 4a,b and appropriate anilines in ethanol was refluxed for 2 h. The reaction mixture was cooled in an ice bath and a drop of sulfuric acid was added to it. The product obtained was filtered, washed and recrystallised by EtOH as shiny reddish yellow crystals.
32. General procedure for the synthesis of 3-chloro-4-(3-methoxy-4-acetyloxyphenyl)-1-[3-oxo-3-(phenylamino)propanamido] azetidin-2-ones 3a-g: In a closed vessel containing compound 2a-g (0.001 M) in 20 mL of 1,4-dioxan, 0.095 mL of chloroacetyl chloride and 0.16 mL of triethylamine were added and the reaction mixture was stirred at 50 °C for 1 h. The reaction mixture was then kept at room temperature for 30 min and further refluxed for 8 h. The filtrate was concentrated under reduced pressure and poured into ice-cold water. The product 3a-g so obtained was recrystallised from methanol as light brown crystals.
33. General procedure for the synthesis of and 3-chloro-4-[2-hydroxy-5-(nitro substituted phenylazo)phenyl]-1-phenylazetidin-2-ones 6a-h: In a closed vessel containing compound 4 (0.001 M) in 20 mL 1,4-dioxan, 0.095 mL of chloroacetyl chloride and 0.16 mL of triethylamine were added and the reaction mixture was stirred at 50 °C for 1 h. The reaction mixture was then kept at room temperature for 30 min and further refluxed for 8 h. The filtrate was left for three days at room temperature and treated with ice-cold water. The coloured solid obtained was filtered, washed and recrystallised from 1:1 methanol + chloroform mixture.
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36. 3,4 = 4.4 Hz, C3-H), 7.1-7.4 (m, 12H, ArH), MS: Elemental analysis, found (calcd) (%) C, 61.23 (61.99): H, 3.18 (3.69); N, 13.41 (13.77).
37. In disc-diffusion assay, few colonies of organisms were inoculated in 2-5 mL nutrient broth and grown for 2.5 h. The agar plates were dried and inoculated by spreading the bacterial suspension evenly over it. The sterile paper discs (6 mm) impregnated with fixed dose viz., 400 μg/mL of compound were placed on the preinoculated surface. The disc-bearing plates were incubated at 37 °C and examined at 48 h for zone of inhibition, if any, around the disc. Chloromycetin was used in assay as a standard control drug. An additional negative control disc without any sample but impregnated with equivalent amount of solvent (DMF) was also used in the assay. The diameter of inhibition zone is directly proportional to the degree of sensitivity of bacterial strain and the concentration of compound under test.
38. In broth dilution assay, different concentrations of compound in the range from 15.62 to 8000 μg/mL in DMF were prepared using Sabouraud's Dextrose media in sterile test tubes and suspension of fungal cultures was inoculated in them. These tube dilutions were incubated at 25 °C for 72 h along with control. Fluconazole was also screened under similar conditions as reference drug. The dilution of a compound showing no visible growth of fungi was taken as minimum inhibitory concentration (MIC) of compound.