ArticleBioorganic & medicinal chemistry letters2011
Identification of SQ609 as a lead compound from a library of dipiperidines.
Article in Bioorganic & medicinal chemistry letters, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- OvercomingActa pharmaceutica Sinica. B · 2022Review
- Natural-Product-Based Solutions for Tropical Infectious Diseases.Clinical microbiology reviews · 2021Review
- Molecule Property Analyses of Active Compounds forJournal of medicinal chemistry · 2020Review
- Structural Modifications of 3-Triazeneindoles and Their Increased Activity AgainstAntibiotics (Basel, Switzerland) · 2020Article
- Ultraviolet Radiation From a Plant Perspective: The Plant-Microorganism Context.Frontiers in plant science · 2020Review
- Synthesis, Antimicrobial, and Anti-Proliferative Activities of Novel 4-(Adamantan-1-yl)-1-arylidene-3-thiosemicarbazides, 4-ArylmethylMolecules (Basel, Switzerland) · 2019Article
- The Biological Activity of Natural Alkaloids against Herbivores, Cancerous Cells and Pathogens.Toxins · 2019Review
- In Vitro Activity of 3-Triazeneindoles against Mycobacterium tuberculosis and Mycobacterium avium.Antimicrobial agents and chemotherapy · 2016Article
- The Biosynthesis of Capuramycin-type Antibiotics: IDENTIFICATION OF THE A-102395 BIOSYNTHETIC GENE CLUSTER, MECHANISM OF SELF-RESISTANCE, AND FORMATION OF URIDINE-5'-CARBOXAMIDE.The Journal of biological chemistry · 2015Article
- Oxa, Thia, Heterocycle, and Carborane Analogues of SQ109: Bacterial and Protozoal Cell Growth Inhibitors.ACS infectious diseases · 2015Article
- Design, development, drug-likeness, and molecular docking studies of novel piperidin-4-imine derivatives as antitubercular agents.Drug design, development and therapy · 2015Article
- Investigational antimicrobial agents of 2013.Clinical microbiology reviews · 2013Review
- Progress in targeting cell envelope biogenesis in Mycobacterium tuberculosis.Future microbiology · 2013Review
- Discovery and development of SQ109: a new antitubercular drug with a novel mechanism of action.Future microbiology · 2012Review
- Chemotherapeutic interventions against tuberculosis.Pharmaceuticals (Basel, Switzerland) · 2012Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
We recently reported that compounds created around a dipiperidine scaffold demonstrated activity against Mycobacterium tuberculosis (Mtb) (Bogatcheva, E.; Hanrahan, C.; Chen, P.; Gearhart, J.; Sacksteder, K.; Einck, L.; Nacy, C.; Protopopova, M. Bioorg. Med. Chem. Lett.2010, 20, 201). To optimize the dipiperidine compound series and to select a lead compound to advance into preclinical studies, we evaluated the structure-activity relationship (SAR) of our proprietary libraries. The (piperidin-4-ylmethyl)piperidine scaffold was an essential structural element required for antibacterial activity. Based on SAR, we synthesized a focused library of 313 new dipiperidines to delineate additional structural features responsible for antitubercular activity. Thirty new active compounds with MIC 10-20 μg/ml on Mtb were identified, but none was better than the original hits of this series, SQ609, SQ614, and SQ615. In Mtb-infected macrophages in vitro, SQ609 and SQ614 inhibited more than 90% of intracellular bacterial growth at 4 μg/ml; SQ615 was toxic to these cells. In mice infected with Mtb, weight loss was completely prevented by SQ609, but not SQ614, and SQ609 had a prolonged therapeutic effect, extended by 10-15 days, after cessation of therapy. Based on in vitro and in vivo antitubercular activity, SQ609 was identified as the best-in-class dipiperidine compound in the series.
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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.