ArticleBioorganic & medicinal chemistry2013
Design, synthesis and anti-tuberculosis activity of 1-adamantyl-3-heteroaryl ureas with improved in vitro pharmacokinetic properties.
Article in Bioorganic & medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 80 citations in OpenAlex.
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- Decoding the selective chemical modulation of CYP3A4.Nature communications · 2025Article
- Novel tetrahydronaphthalen-1-yl-phenethyl ureas: synthesis and dual antibacterial-anticancer activities.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- Development of Brain Penetrant Pyridazine Pantothenate Kinase Activators.Journal of medicinal chemistry · 2024Article
- Isoxazole carboxylic acid methyl ester-based urea and thiourea derivatives as promising antitubercular agents.Molecular diversity · 2023Article
- Recent advances in mycobacterial membrane protein large 3 inhibitor drug design for mycobacterial infections.Expert opinion on drug discovery · 2023Review
- Molecular Mechanisms of MmpL3 Function and Inhibition.Microbial drug resistance (Larchmont, N.Y.) · 2023Review
- Adamantyl-ureas with pyrazoles substituted by fluoroalkanes as soluble epoxide hydrolase inhibitors.Journal of fluorine chemistry · 2023Article
- Structural Determinants of Indole-2-carboxamides: Identification of Lead Acetamides with Pan Antimycobacterial Activity.Journal of medicinal chemistry · 2023Article
- Molecular insights into Mmpl3 leads to the development of novel indole-2-carboxamides as antitubercular agents.Molecular systems design & engineering · 2022Article
- Synthesis and Structure-Activity Relationship of Thioacetamide-Triazoles againstMolecules (Basel, Switzerland) · 2022Article
- LipE guided discovery of isopropylphenyl pyridazines as pantothenate kinase modulators.Bioorganic & medicinal chemistry · 2021Article
- Pipeline of anti-Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities.Medicinal research reviews · 2021Review
- Mycobacterial Epoxide Hydrolase EphD Is Inhibited by Urea and Thiourea Derivatives.International journal of molecular sciences · 2021Article
- Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets.Frontiers in cellular and infection microbiology · 2021Review
- 2-Oxaadamant-1-yl Ureas as Soluble Epoxide Hydrolase Inhibitors:Journal of medicinal chemistry · 2020Article
- Ureadepsipeptides as ClpP Activators.ACS infectious diseases · 2019Article
- Fluoroaromatic fragments on 1,3-disubstituted ureas enhance soluble epoxide hydrolase inhibition.Journal of fluorine chemistry · 2019Article
- Discovery of Novel Soluble Epoxide Hydrolase Inhibitors as Potent Vasodilators.Scientific reports · 2018Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Out of the prominent global ailments, tuberculosis (TB) is still one of the leading causes of death worldwide due to infectious disease. Development of new drugs that shorten the current tuberculosis treatment time and have activity against drug resistant strains is of utmost importance. Towards these goals we have focused our efforts on developing novel anti-TB compounds with the general structure of 1-adamantyl-3-phenyl urea. This series is active against Mycobacteria and previous lead compounds were found to inhibit the membrane transporter MmpL3, the protein responsible for mycolic acid transport across the plasma membrane. However, these compounds suffered from poor in vitro pharmacokinetic (PK) profiles and they have a similar structure/SAR to inhibitors of human soluble epoxide hydrolase (sEH) enzymes. Therefore, in this study the further optimization of this compound class was driven by three factors: (1) to increase selectivity for anti-TB activity over human sEH activity, (2) to optimize PK profiles including solubility and (3) to maintain target inhibition. A new series of 1-adamantyl-3-heteroaryl ureas was designed and synthesized replacing the phenyl substituent of the original series with pyridines, pyrimidines, triazines, oxazoles, isoxazoles, oxadiazoles and pyrazoles. This study produced lead isoxazole, oxadiazole and pyrazole substituted adamantyl ureas with improved in vitro PK profiles, increased selectivity and good anti-TB potencies with sub μg/mL minimum inhibitory concentrations.
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