Quinazolinone-based fungal efflux pump inhibitors. Part 1: Discovery of an (N-methylpiperazine)-containing derivative with activity in clinically relevant Candida spp

The discovery of a series of quinazolinone-based fungal efflux pump inhibitors by high-throughput screening for potentiation of fluconazole in C. albicans is described. Attempts to improve the aqueous solubility of screening hits led to the discovery of an analog with greatly improved physical prope...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2004-10, Vol.14 (20), p.5127-5131
Main Authors: Lemoine, Rémy C., Glinka, Tomasz W., Watkins, William J., Cho, Aesop, Yang, Jessie, Iqbal, Nadeem, Singh, Rajeshwar, Madsen, Deidre, Lolans, Karen, Lomovskaya, Olga, Oza, Uma, Dudley, Michael N.
Format: Article
Language:English
Subjects:
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antifungal agents
Antifungal Agents - chemical synthesis
Antifungal Agents - pharmacology
ATP-Binding Cassette Transporters - antagonists & inhibitors
Biological and medical sciences
Candida - drug effects
Candida - enzymology
Drug Resistance, Fungal
Drug Synergism
Fluconazole - chemistry
Fluconazole - pharmacology
Fungal Proteins - antagonists & inhibitors
Humans
In Vitro Techniques
Medical sciences
Membrane Transport Modulators
Membrane Transport Proteins - antagonists & inhibitors
Models, Molecular
Pharmacology. Drug treatments
Piperazines - chemical synthesis
Piperazines - chemistry
Piperazines - pharmacology
Quinazolines - chemical synthesis
Quinazolines - chemistry
Quinazolines - pharmacology
Solubility
Stereoisomerism
Structure-Activity Relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The discovery of a series of quinazolinone-based fungal efflux pump inhibitors by high-throughput screening for potentiation of fluconazole in C. albicans is described. Attempts to improve the aqueous solubility of screening hits led to the discovery of an analog with greatly improved physical properties and activity against clinically-relevant Candida spp. The discovery of a series of quinazolinone-based fungal efflux pump inhibitors by high-throughput screening for potentiation of fluconazole in C. albicans is described. Attempts to improve the aqueous solubility of screening hits led to the discovery of an analog with greatly improved physical properties and activity against clinically-relevant Candida spp.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2004.07.070