ArticleJournal of medicinal chemistry2013
Structure-activity relationship and in vitro and in vivo evaluation of the potent cytotoxic anti-microtubule agent N-(4-methoxyphenyl)-N,2,6-trimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-aminium chloride and its analogues as antitumor agents.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed.
- Discovery and biological evaluation of nitrofuranyl-pyrazolopyrimidine hybrid conjugates as potent antimicrobial agents targetingRSC medicinal chemistry · 2025Article
- Design, Synthesis, Evaluation and Molecular Dynamics Simulation of Dengue Virus NS5-RdRp Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Verubulin (Azixa) Analogues with Increased Saturation: Synthesis, SAR and Encapsulation in Biocompatible Nanocontainers Based on CaPharmaceuticals (Basel, Switzerland) · 2023Article
- Novel Nanomolar Allosteric Modulators of AMPA Receptor of Bis(pyrimidine) Series: Synthesis, Biotesting and SAR Analysis.Molecules (Basel, Switzerland) · 2022Article
- Hybrid Drugs-A Strategy for Overcoming Anticancer Drug Resistance?Molecules (Basel, Switzerland) · 2021Review
- The 3-D conformational shape of N-naphthyl-cyclopenta[d]pyrimidines affects their potency as microtubule targeting agents and their antitumor activity.Bioorganic & medicinal chemistry · 2021Article
- Structure based drug design and in vitro metabolism study: Discovery of N-(4-methylthiophenyl)-N,2-dimethyl-cyclopenta[d]pyrimidine as a potent microtubule targeting agent.Bioorganic & medicinal chemistry · 2018Article
- Design, synthesis, and structure-activity relationships of pyrimido[4,5-b]indole-4-amines as microtubule depolymerizing agents that are effective against multidrug resistant cells.Bioorganic & medicinal chemistry letters · 2017Article
- Janus Compounds, 5-Chloro-N⁴-methyl-N⁴-aryl-9H-pyrimido[4,5-b]indole-2,4-diamines, Cause Both Microtubule Depolymerizing and Stabilizing Effects.Molecules (Basel, Switzerland) · 2016Article
- Design, Synthesis, and Preclinical Evaluation of 4-Substituted-5-methyl-furo[2,3-d]pyrimidines as Microtubule Targeting Agents That Are Effective against Multidrug Resistant Cancer Cells.Journal of medicinal chemistry · 2016Article
- Biological Characterization of an Improved Pyrrole-Based Colchicine Site Agent Identified through Structure-Based Design.Molecular pharmacology · 2016Article
- The design and discovery of water soluble 4-substituted-2,6-dimethylfuro[2,3-d]pyrimidines as multitargeted receptor tyrosine kinase inhibitors and microtubule targeting antitumor agents.Bioorganic & medicinal chemistry · 2014Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
A series of 21 substituted cyclopenta[d]pyrimidines were synthesized as an extension of our discovery of the parent compound (±)-1·HCl as an anti-microtubule agent. The structure-activity relationship indicates that the N-methyl and a 4N-methoxy groups appear important for potent activity. In addition, the 6-substituent in the parent analogue is not necessary for activity. The most potent compound 30·HCl was a one to two digit nanomolar inhibitor of most tumor cell proliferations and was up to 7-fold more potent than the parent compound (±)-1·HCl. In addition, 30·HCl inhibited cancer cell proliferation regardless of Pgp or βIII-tubulin status, both of which are known to cause clinical resistance to several anti-tubulin agents. In vivo efficacy of 30·HCl was demonstrated against a triple negative breast cancer xenograft mouse model. Compound 30·HCl is water-soluble and easily synthesized and serves as a lead compound for further preclinical evaluation as an antitumor agent.
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