As part of a detailed study, the syntheses, biological activities, and pharmacokinetic properties of hydroxylated analogues of the previously described broad spectrum antifungal agents, Sch 51048 (1), Sch 50001 (3), and Sch 50002 (4), are described. Based on an overall superior profile, one of the alcohols, Sch 56592 (2), was selected for clinical studies.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2005.09.031DOI Listing

Publication Analysis

Top Keywords

hydroxylated analogues
8
broad spectrum
8
spectrum antifungal
8
sch 51048
8
sch
5
analogues orally
4
orally active
4
active broad
4
antifungal sch
4
51048 discovery
4

Similar Publications

[Current advances in the analysis of free RNA modified nucleosides by high performance liquid chromatography-tandem mass spectrometry].

Se Pu

January 2025

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China;3. University of Chinese Academy of Sciences, Beijing 100049, China.

Post-transcriptional ribonucleic acid (RNA) modifications play crucial roles in regulating gene expression, with both eukaryotic and prokaryotic RNA exhibiting more than 170 distinct and ubiquitous modifications. RNA turnover generates numerous free nucleosides, including unmodified nucleosides and a variety of modified ones. Unlike unmodified nucleosides, modified nucleosides are not further degraded or used in the salvage-synthesis pathway owing to a lack of specific enzymes, which leads to the cytosolic accumulation or cellular efflux of modified nucleosides.

View Article and Find Full Text PDF

[Advances in epigenetic regulation of the dioxygenase TET1].

Sheng Wu Gong Cheng Xue Bao

December 2024

College of Veterinary Medicine, Southwest University, Chongqing 402460, China.

Ten-eleven translocation 1 (TET1) protein is an alpha-ketoglutaric acid (α-KG) and Fe-dependent dioxygenase. It plays a role in the active demethylation of DNA by hydroxylation of 5-methyl-cytosine (5-mC) to 5-hydroxymethyl-cytosine (5-hmC). Ten-eleven translocation 1 (TET1) protein is involved in maintaining genome methylation homeostasis and epigenetic regulation.

View Article and Find Full Text PDF

Lycorine esters exert anti-HCoV-OC43 effect through reversibly acylating cysteine residue in the nsp 12 NiRAN domain.

Bioorg Chem

December 2024

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China. Electronic address:

By introducing ester warheads into the hydroxyl groups in lycorine (1), three types of lycorine mono-ester or di-ester analogues were synthesized and evaluated for their antiviral activities against HCoV-OC43. Most of them showed higher selective indexes (SI) than 1, up to nearly 14 times. Using compound 6b as a probe, we firstly demonstrated that lycorine esters directly targeted nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain in the non-structural protein 12 (nsp 12) by reversibly acylating Cys12 to induce the shrink of NiRAN pocket and block the viral replication, different from the known RdRp inhibitors.

View Article and Find Full Text PDF

Synthesis, crystal structure and absolute configuration of (3a,4,5,7a)-7-(but-3-en-1-yn-1-yl)-2,2-dimethyl-3a,4,5,7a-tetra-hydro-2-1,3-benzodioxole-4,5-diol.

Acta Crystallogr E Crystallogr Commun

October 2024

Cryssmat-Lab, Cátedra de Física, DETEMA, Facultad de Química, Universidad de la República, Av. General Flores 2124, CP 11800, Montevideo, Uruguay.

Article Synopsis
  • The absolute configuration of the compound CHO was determined and confirmed through single-crystal X-ray diffraction.
  • CHO serves as an important intermediate for synthesizing speciosins, epoxy-quinoides, or their analogues.
  • The molecular structure features fused five- and six-membered rings with hydroxyl groups, and its packing is influenced by hydrogen bonds and van der Waals interactions.
View Article and Find Full Text PDF

Bicarbonate ions promote rapid degradation of pollutants in Co(II)Fe(II)/peroxyacetic acid systems.

J Hazard Mater

December 2024

School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning Province 110016, PR China. Electronic address:

Peroxyacetic acid (PAA), as an oxidizing agent, has gained significant attention in the field of advanced oxidation because of its low toxicity and high degradation capacity. In this study, cobalt-iron-based Prussian blue analogs (Co-PBAs) were utilized for the first time to activate PAA for tetracycline degradation. In the Co-PBAs/PAA system, organic radicals (RO•) and high-valent metal oxides are mainly produced.

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!