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Chemical Structure| 122536-76-9 Chemical Structure| 122536-76-9
Chemical Structure| 122536-76-9

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Canale, Vittorio ; Czekajewska, Joanna ; Klesiewicz, Karolina ; Papiez, Monika ; Kuziak, Agata ; Witek, Karolina , et al.

Abstract: The alarming increase in the resistance of bacteria to the currently available antibiotics necessitates the development of new effective antimicrobial agents that are active against bacterial pathogens causing major public health problems. For this purpose, our inhouse libraries were screened against a wide panel of clin. relevant Gram-pos. and Gram-neg. bacteria, based on which compound I was selected for further optimization. Synthetic efforts in a group of arylurea derivatives of aryloxy(1-phenylpropyl) alicyclic diamines, followed with an in vitro evaluation of the activity against multidrug-resistant strains identified compound 44 (1-(3-chlorophenyl)-3-(1-{3-phenyl-3-[3-(trifluoromethyl)phenoxy] propyl}piperidin-4-yl)urea). Compound 44 showed antibacterial activity against Gram-pos. bacteria including fatal drug-resistant strains i.e., Staphylococcus aureus (methicillin-resistant, MRSA; vancomycin-intermediate, VISA) and Enterococcus faecium (vancomycin-resistant, VREfm) at low concentrations (0.78-3.125 μg/mL) comparable to last resort antibiotics (i.e., vancomycin and linezolid). It is also potent against biofilm-forming S. aureus and Staphylococcus epidermidis (including linezolid-resistant, LRSE) strains, but with no activity against Gram-neg. bacteria (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa). Compound 44 showed strong bactericidal properties against susceptible and drug-resistant Gram-pos. bacteria. Depolarization of the bacterial cytoplasmic membrane induced by compound 44 suggests a dissipation of the bacterial membrane potential as its mechanism of antibacterial action. The high antimicrobial activity of compound 44, along with its selectivity over mammalian cells (lung MCR-5 and skin BJ fibroblast cell lines) and no hemolytic properties toward horse erythrocytes, proposes arylurea derivatives of aryloxy(1-phenylpropyl) alicyclic diamines for development of novel antibacterial agents.

Keywords: Arylurea derivatives ; Antibacterial properties ; Anti-MRSA activity ; Anti-VRE activity ; Anti-LRSE activity ; Depolarization of bacterial cell membrane

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Product Details of (S)-3-(Boc-amino)pyrrolidine

CAS No. :122536-76-9
Formula : C9H18N2O2
M.W : 186.25
SMILES Code : O=C(OC(C)(C)C)N[C@@H]1CNCC1
MDL No. :MFCD00143194
InChI Key :DQQJBEAXSOOCPG-ZETCQYMHSA-N
Pubchem ID :1514396

Safety of (S)-3-(Boc-amino)pyrrolidine

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of (S)-3-(Boc-amino)pyrrolidine

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 122536-76-9 ]
  • Downstream synthetic route of [ 122536-76-9 ]

[ 122536-76-9 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 100-52-7 ]
  • [ 122536-76-9 ]
  • [ 131852-53-4 ]
YieldReaction ConditionsOperation in experiment
84%
Stage #1: at 20℃; for 0.166667 h;
Stage #2: With sodium tris(acetoxy)borohydride In 1,2-dichloro-ethane; N,N-dimethyl-formamide at 20℃; for 5 h;
EXAMPLE 67 Synthesis of (S)-4-((1-benzylpyrrolidin-3-yl)amino)-3-chloro-/V-(1 ,2,4-thiadiazol-5- yl)benzenesulfonamide 2,2,2-trifluoroacetate Step 1. Preparation of te/f-butyl (S)-(1-benzylpyrrolidin-3-yl)carbamate To a solution of terf-butyl (S)-pyrrolidin-3-ylcarbamate (0.30 g, 1.60 mmol) in anhydrous 1 ,2-dichloroethane (2 mL) and anhydrous A/,A/-dimethylformamide (2 mL) was added benzaldehyde (0.26 g, 2.40 mmol). The reaction mixture was stirred at ambient temperature for 10 minutes and then sodium triacetoxyborohydride (0.68 g, 3.20 mmol) was added to it. The reaction mixture was stirred at ambient temperature for 5 h. After dilution with ethyl acetate (50 mL), the mixture was washed with brine (3 x 50 mL), dried over anhydrous sodium sulfate, and filtered. Concentration of the filtrate in vacuo provided the title compound as colorless oil (0.37 g, 84 percent yield). H NMR (300 MHz, CDCI3) 7.58-7.53 (m, 2H), 7.46-7.39 (m, 3H), 4.55-4.49 (m, 1 H), 4.16 (s, 2H), 3.67-3.52 (m, 1 H), 3.40-3.36 (m, 1 H), 3.12-3.06 (m, 1 H), 2.91-2.81 (m, 1 H), 2.52-2.40 (m, 1 H), 2.25-2.12 (m, 1 H), 1.39 (s, 9H), NH not observed; MS (ES+) m/z 277.2 (M + 1).
References: [1] Patent: WO2017/201468, 2017, A1, . Location in patent: Page/Page column 180-181.
 

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