ArticleBioorganic & medicinal chemistry2011
The structure-activity relationship of urea derivatives as anti-tuberculosis agents.
Article in Bioorganic & medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 105 citations in OpenAlex.
- Novel Thiourea Ligands-Synthesis, Characterization and Preliminary Study on Their Coordination Abilities.Molecules (Basel, Switzerland) · 2024Article
- Direct additive-free N-formylation and N-acylation of anilines and synthesis of urea derivatives using green, efficient, and reusable deep eutectic solvent ([ChCl][ZnClScientific reports · 2024Article
- Isoxazole carboxylic acid methyl ester-based urea and thiourea derivatives as promising antitubercular agents.Molecular diversity · 2023Article
- Structure-directed identification of pyridine-2-methylamine derivatives as MmpL3 inhibitors for use as antitubercular agents.European journal of medicinal chemistry · 2023Article
- Recent advances in mycobacterial membrane protein large 3 inhibitor drug design for mycobacterial infections.Expert opinion on drug discovery · 2023Review
- Tuberculosis: Pathogenesis, Current Treatment Regimens and New Drug Targets.International journal of molecular sciences · 2023Review
- Structural Determinants of Indole-2-carboxamides: Identification of Lead Acetamides with Pan Antimycobacterial Activity.Journal of medicinal chemistry · 2023Article
- An anti-tuberculosis compound screen using a zebrafish infection model identifies an aspartyl-tRNA synthetase inhibitor.Disease models & mechanisms · 2021Article
- Recent advances in urea- and thiourea-containing compounds: focus on innovative approaches in medicinal chemistry and organic synthesis.RSC medicinal chemistry · 2021Review
- Mycobacterial Epoxide Hydrolase EphD Is Inhibited by Urea and Thiourea Derivatives.International journal of molecular sciences · 2021Article
- Design, synthesis and antimycobacterial evaluation of novel adamantane and adamantanol analogues effective against drug-resistant tuberculosis.Bioorganic chemistry · 2021Article
- Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets.Frontiers in cellular and infection microbiology · 2021Review
- Chromatography-Free Multicomponent Synthesis of Thioureas Enabled by Aqueous Solution of Elemental Sulfur.ChemistryOpen · 2021Article
- The crystal structure of mycobacterial epoxide hydrolase A.Scientific reports · 2020Article
- 2-Oxaadamant-1-yl Ureas as Soluble Epoxide Hydrolase Inhibitors:Journal of medicinal chemistry · 2020Article
- Article
- Exploring the size of the lipophilic unit of the soluble epoxide hydrolase inhibitors.Bioorganic & medicinal chemistry · 2019Article
- Pentafluorosulfanyl-containing Triclocarban Analogs with Potent Antimicrobial Activity.Molecules (Basel, Switzerland) · 2018Article
- Synthesis and In Vitro Antiproliferative Activity of New 1-Phenyl-3-(4-(pyridin-3-yl)phenyl)urea Scaffold-Based Compounds.Molecules (Basel, Switzerland) · 2018Article
- MmpL3 as a Target for the Treatment of Drug-Resistant Nontuberculous Mycobacterial Infections.Frontiers in microbiology · 2018Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
The treatment of tuberculosis is becoming more difficult due to the ever increasing prevalence of drug resistance. Thus, it is imperative that novel anti-tuberculosis agents, with unique mechanisms of action, be discovered and developed. The direct anti-tubercular testing of a small compound library led to discovery of adamantyl urea hit compound 1. In this study, the hit was followed up through the synthesis of an optimization library. This library was generated by systematically replacing each section of the molecule with a similar moiety until a clear structure-activity relationship was obtained with respect to anti-tubercular activity. The best compounds in this series contained a 1-adamantyl-3-phenyl urea core and had potent activity against Mycobacterium tuberculosis plus an acceptable therapeutic index. It was noted that the compounds identified and the pharmacophore developed is consistent with inhibitors of epoxide hydrolase family of enzymes. Consequently, the compounds were tested for inhibition of representative epoxide hydrolases: M. tuberculosis EphB and EphE; and human soluble epoxide hydrolase. Many of the optimized inhibitors showed both potent EphB and EphE inhibition suggesting the antitubercular activity is through inhibition of multiple epoxide hydrolase enzymes. The inhibitors also showed potent inhibition of humans soluble epoxide hydrolase, but limited cytotoxicity suggesting that future studies must be towards increasing the selectivity of epoxide hydrolase inhibition towards the M. tuberculosis enzymes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.