Abstract
A series of thioamides were designed as bio-isosteres to the non-nucleoside reverse transcriptase inhibitor trovirdine by replacement of the thiourea NH groups with methylene groups. Eight thioamides were synthesized and in vitro tested for inhibitory effects on the activity of HIV-1 reverse transcriptase wild and mutant types. Three of the 8- thioamides exhibited enzyme inhibitory activities with IC50 values below 100 μM. While compound (2) exhibited activity against the mutant strain L100I with IC50 of 70.1 μM, compound (4) showed activity against the mutant strain K103N with IC50 of 92.7 μM, and compound (8) with activity against the wild type enzyme with IC50 of 8.9 μM. Each of the three thioamides could serve as a lead compound for further activity optimization.
Keywords: Non-nucleoside reverse transcriptase inhibitors, PETT bio-isosteres, thioamides
Medicinal Chemistry
Title: Design, Synthesis and Biological Evaluation of a Series of Thioamides as Non-Nucleoside Reverse Transcriptase Inhibitors
Volume: 3 Issue: 6
Author(s): Ahmed S. Mehanna, Jitendra D. Belani, Charles J. Kelley and Luke A. Pallansch
Affiliation:
Keywords: Non-nucleoside reverse transcriptase inhibitors, PETT bio-isosteres, thioamides
Abstract: A series of thioamides were designed as bio-isosteres to the non-nucleoside reverse transcriptase inhibitor trovirdine by replacement of the thiourea NH groups with methylene groups. Eight thioamides were synthesized and in vitro tested for inhibitory effects on the activity of HIV-1 reverse transcriptase wild and mutant types. Three of the 8- thioamides exhibited enzyme inhibitory activities with IC50 values below 100 μM. While compound (2) exhibited activity against the mutant strain L100I with IC50 of 70.1 μM, compound (4) showed activity against the mutant strain K103N with IC50 of 92.7 μM, and compound (8) with activity against the wild type enzyme with IC50 of 8.9 μM. Each of the three thioamides could serve as a lead compound for further activity optimization.
Export Options
About this article
Cite this article as:
Mehanna S. Ahmed, Belani D. Jitendra, Kelley J. Charles and Pallansch A. Luke, Design, Synthesis and Biological Evaluation of a Series of Thioamides as Non-Nucleoside Reverse Transcriptase Inhibitors, Medicinal Chemistry 2007; 3 (6) . https://dx.doi.org/10.2174/157340607782360344
DOI https://dx.doi.org/10.2174/157340607782360344 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers