Synthesis and in Vitro Anti-Mycobacterium Activity of N-Alkyl-1,2-dihydro-2-thioxo-3-pyridinecarbothioamides. Preliminary Toxicity and Pharmacokinetic Evaluation
- 1 January 2000
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 43 (2) , 199-204
- https://doi.org/10.1021/jm991044p
Abstract
Disseminated infections with Mycobacterium tuberculosis (MT) and Mycobacterium avium complex (MAC) are increasingly opportunistic diseases in patients with advanced acquired human immunodeficiency syndrome (AIDS). A series of N-alkyl-1, 2-dihydro-2-thioxo-3-pyridinecarbothioamides has been synthesized, and MICs for MT and MAC strains, either standard or isolated from infected patients, have been determined. Preliminary tests show a good activity and a very low toxicity for some derivatives. Pharmacokinetic studies in the rat show a very rapid elimination from the body after intravenous administration and a poor absorption after oral administration.Keywords
This publication has 15 references indexed in Scilit:
- Antimicrobial activity of N-hydroxyalkyl 1,2-benzisothiazol-3(2H) -ones and their thiono analoguesEuropean Journal of Medicinal Chemistry, 1996
- In Vitro Anti‐Mycobacterium avium Activity of N‐(2‐Hydroxyethyl)‐1,2‐benzisothiazol‐3(2H)‐one and ‐thione Carbamic EstersArchiv der Pharmazie, 1996
- Synthesis of 3H‐thieno[3,2‐c]‐1,2‐dithiole‐3‐thione and its reaction with n‐butylamineJournal of Heterocyclic Chemistry, 1995
- ReplyClinical Infectious Diseases, 1994
- Clinical Manifestations of AIDS in the Era of Pneumocystis ProphylaxisNew England Journal of Medicine, 1993
- Recommendations on Prophylaxis and Therapy for Disseminated Mycobacterium avium Complex Disease in Patients Infected with the Human Immunodeficiency VirusNew England Journal of Medicine, 1993
- On the reaction between 3H‐1,2‐dithiolo[3,4‐b]pyridine‐3‐thione and primary alkyl and arylalkylaminesJournal of Heterocyclic Chemistry, 1993
- Mycobacterium avium Infection and AIDS: A Therapeutic Dilemma in Rapid EvolutionThe Journal of Infectious Diseases, 1991
- Atomic physicochemical parameters for three-dimensional-structure-directed quantitative structure-activity relationships. 2. Modeling dispersive and hydrophobic interactionsJournal of Chemical Information and Computer Sciences, 1987
- Renin inhibitors. Syntheses of subnanomolar, competitive, transition-state analog inhibitors containing a novel analog of statineJournal of Medicinal Chemistry, 1985