ArticleJournal of medicinal chemistry2010
Synthesis and discovery of water-soluble microtubule targeting agents that bind to the colchicine site on tubulin and circumvent Pgp mediated resistance.
Article in Journal of medicinal chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
26 citing papers in PubMed.
- Novel Triazoloquinoxaline-Based Tubulin Polymerization Inhibitor Induces Necroptosis and Significantly Inhibits Metastatic Melanoma Tumor Growth.Journal of medicinal chemistry · 2026Article
- Novel Brain-Penetrant, Small-Molecule Tubulin Destabilizers for the Treatment of Glioblastoma.Biomedicines · 2024Article
- Verubulin (Azixa) Analogues with Increased Saturation: Synthesis, SAR and Encapsulation in Biocompatible Nanocontainers Based on CaPharmaceuticals (Basel, Switzerland) · 2023Article
- Simple monocyclic pyrimidine analogs as microtubule targeting agents binding to the colchicine site.Bioorganic & medicinal chemistry · 2023Article
- X-ray Crystallography-Guided Design, Antitumor Efficacy, and QSAR Analysis of Metabolically Stable Cyclopenta-Pyrimidinyl Dihydroquinoxalinone as a Potent Tubulin Polymerization Inhibitor.Journal of medicinal chemistry · 2021Article
- 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
- Colchicine Binding Site Agent DJ95 Overcomes Drug Resistance and Exhibits Antitumor Efficacy.Molecular pharmacology · 2019Article
- Structure Guided Design, Synthesis, and Biological Evaluation of Novel Benzosuberene Analogues as Inhibitors of Tubulin Polymerization.Journal of medicinal chemistry · 2019Article
- Sterically induced conformational restriction: Discovery and preclinical evaluation of novel pyrrolo[3,2-d]pyrimidines as microtubule targeting agents.Bioorganic & medicinal chemistry · 2018Article
- SQ1274, a novel microtubule inhibitor, inhibits ovarian and uterine cancer cell growth.Gynecologic oncology · 2018Article
- 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
- Heterocyclic-Fused Pyrimidines as Novel Tubulin Polymerization Inhibitors Targeting the Colchicine Binding Site: Structural Basis and Antitumor Efficacy.Journal of medicinal chemistry · 2018Article
- Discovery and preclinical evaluation of 7-benzyl-N-(substituted)-pyrrolo[3,2-d]pyrimidin-4-amines as single agents with microtubule targeting effects along with triple-acting angiokinase inhibition as antitumor agents.Bioorganic & medicinal chemistry · 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
- 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
- How to deal with low-resolution target structures: using SAR, ensemble docking, hydropathic analysis, and 3D-QSAR to definitively map the αβ-tubulin colchicine site.Journal of medicinal chemistry · 2013Article
- 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.Journal of medicinal chemistry · 2013Article
- Exploring natural product chemistry and biology with multicomponent reactions. 5. Discovery of a novel tubulin-targeting scaffold derived from the rigidin family of marine alkaloids.Journal of medicinal chemistry · 2013Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors.
Funding
Abstract
Two classes of molecules were designed and synthesized based on a 6-CH(3) cyclopenta[d]pyrimidine scaffold and a pyrrolo[2,3-d]pyrimidine scaffold. The pyrrolo[2,3-d]pyrimidines were synthesized by reacting ethyl 2-cyano-4,4-diethoxybutanoate and acetamidine, which in turn was chlorinated and reacted with the appropriate anilines to afford 1 and 2. The cyclopenta[d]pyrimidines were obtained from 3-methyladapic acid, followed by reaction with acetamidine to afford the cyclopenta[d]pyrimidine scaffold. Chlorination and reaction with appropriate anilines afforded (±)-3·HCl-(±)-7·HCl. Compounds 1 and (±)-3·HCl had potent antiproliferative activities in the nanomolar range. Compound (±)-3·HCl is significantly more potent than 1. Mechanistic studies showed that 1 and (±)-3·HCl cause loss of cellular microtubules, inhibit the polymerization of purified tubulin, and inhibit colchicine binding. Modeling studies show interactions of these compounds within the colchicine site. The identification of these new inhibitors that can also overcome clinically relevant mechanisms of drug resistance provides new scaffolds for colchicine site agents.
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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.