Aryl urea analogs with broad-spectrum antibacterial activity.

Bioorg Med Chem Lett

Ibis Therapeutics, A Division of Isis Pharmaceuticals, Inc., 1891 Rutherford Road, Carlsbad, CA 92008, USA.

Published: November 2004

The preparation and evaluation of novel aryl urea analogs as broad-spectrum antibacterial agents is described. Numerous compounds showed low micromolar minimum inhibitory concentrations (MIC) against both Gram-positive and Gram-negative bacteria. Selected analogs also exhibited in vivo efficacy in a lethal murine model of bacterial septicemia.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2004.08.059DOI Listing

Publication Analysis

Top Keywords

aryl urea
8
urea analogs
8
analogs broad-spectrum
8
broad-spectrum antibacterial
8
antibacterial activity
4
activity preparation
4
preparation evaluation
4
evaluation novel
4
novel aryl
4
antibacterial agents
4

Similar Publications

Article Synopsis
  • A dinuclear molybdenum complex combined with urea hydrogen peroxide has been developed as an effective catalyst for converting thiols into uronium sulfonate salts with high yields (89-98%) in ethanol at room temperature.
  • The reaction produced hydrogen gas, a pioneering finding in similar oxidation processes, and detailed product characterization was conducted using techniques like FTIR, NMR, and single crystal X-ray diffraction.
  • Mechanistic studies revealed intermediate products including disulfides and sulfinic acids, while two specific reactions illustrated the conversion of uronium p-chlorobenzene sulfonate to sulfonic acid and diphenyl diselenide to selenonate salt.
View Article and Find Full Text PDF

Urea hydrogen-bond donor strengths: bigger is not always better.

Phys Chem Chem Phys

December 2024

Department of Chemistry and Pharmaceutical Sciences, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.

The hydrogen-bond donor strength of ureas, widely used in hydrogen-bond donor catalysis, molecular recognition, and self-assembly, can be enhanced by increasing the size of the chalcogen X in the CX bond from O to S to Se and by introducing more electron-withdrawing substituents because both modifications increase the positive charge on the NH groups which become better hydrogen-bond donors. However, in 1,3-diaryl X-ureas, a steric mechanism disrupts the positive additivity of these two tuning factors, as revealed by our quantum-chemical analyses. This leads to an enhanced hydrogen-bond donor strength, despite a lower NH acidity, for 1,3-diaryl substituted O-ureas compared to the S- and Se-urea analogs.

View Article and Find Full Text PDF

Pendrin (SLC26A4) is an anion exchanger expressed in epithelial cells of kidney and lung. Pendrin inhibition is a potential treatment approach for edema, hypertension and inflammatory lung diseases. We have previously identified first-in-class pendrin inhibitors by high-throughput screening, albeit with low potency for pendrin inhibition (IC ∼10 μM).

View Article and Find Full Text PDF

To investigate the therapeutic potential of 5-Fluorouracil-based analogues, a straightforward synthetic technique was employed to synthesize a novel series of 5-arylurea uracil derivatives (AUFU01-03) and aryl-urea derivatives bearing perfluorophenyl (AUPF01-03). Reliable tools such as infrared (IR), Nuclear Magnetic Resonance (NMR) spectra, and elemental analyses were utilized to confirm the chemical structures and purity of these compounds. In comparison to healthy noncancerous control skin fibroblast cells (BJ-1), we examined the antiproliferative efficacy of compounds (AUFU01-03) and (AUPF01-03) against specific human malignant cell lines of the breast (MCF-7), and colon (HCT-116).

View Article and Find Full Text PDF

Urease catalyzes the hydrolysis of urea, leading to an increase in stomach pH and supporting Helicobacter pylori survival, which is linked to several gastrointestinal disorders. In this study, thiazine-based Schiff bases were explored as promising urease inhibitors. Various spectroscopic techniques characterized the synthetic library of thiazine Schiff bases 2-36 and also evaluated for their inhibitory activities against urease.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!