New N-Alkyl-1,2-dihydro-2-thioxo-3-pyridinecarbothioamides as antituberculous agents with improved pharmacokinetics

Infections caused by multidrug-resistant Mycobacterium tuberculosis (MT) and non-tuberculous mycobacteria are difficult to treat and, indeed, new therapeutic agents are being sought. As a part of an ongoing research in our laboratories, novel N-alkyl-1,2-dihydro-2-thioxo-3-pyridinecarbothioamides ha...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2002-09, Vol.12 (18), p.2541-2544
Main Authors: Ubiali, Daniela, Pagani, Giuseppe, Pregnolato, Massimo, Piersimoni, Claudio, Pedraz Muñoz, José L., Rodrı́guez Gascón, Alicia, Terreni, Marco
Format: Article
Language:English
Subjects:
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antitubercular Agents - chemistry
Antitubercular Agents - pharmacokinetics
Antitubercular Agents - pharmacology
Biological and medical sciences
Biological Availability
Magnetic Resonance Spectroscopy
Medical sciences
Mycobacterium avium Complex - drug effects
Mycobacterium tuberculosis - drug effects
Pharmacology. Drug treatments
Pyridines - chemistry
Pyridines - pharmacokinetics
Pyridines - pharmacology
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:Infections caused by multidrug-resistant Mycobacterium tuberculosis (MT) and non-tuberculous mycobacteria are difficult to treat and, indeed, new therapeutic agents are being sought. As a part of an ongoing research in our laboratories, novel N-alkyl-1,2-dihydro-2-thioxo-3-pyridinecarbothioamides have been synthesized and evaluated against several strains of MT and Mycobacterium avium complex (MAC). The pharmacokinetics and relative bioavailability after intravenous administration of three derivatives have been investigated. Introduction of a hydroxyl or a tertiary amino group in the N-alkyl chain resulted in an improved pharmacokinetic profile without affecting sensitively the antituberculous potency. The in vitro antimycobacterial activity and pharmacokinetics of novel N-alkyl-1,2-dihydro-2-thioxo-3-pyridinecarbothioamides are reported.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(02)00490-0