ArticleACS medicinal chemistry letters2011
Discovery of a Potent HIV Integrase Inhibitor that Leads to a Prodrug with Significant anti-HIV Activity.
Article in ACS medicinal chemistry letters, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- Recent Developments in the Synthesis of HIV-1 Integrase Strand Transfer Inhibitors Incorporating Pyridine Moiety.International journal of molecular sciences · 2023Review
- Recent Advances of Pyridinone in Medicinal Chemistry.Frontiers in chemistry · 2022Review
- Advanced Prodrug Strategies in Nucleoside and Non-Nucleoside Antiviral Agents: A Review of the Recent Five Years.Molecules (Basel, Switzerland) · 2017Review
- Progress in HIV-1 Integrase Inhibitors: A Review of their Chemical Structure Diversity.Iranian journal of pharmaceutical research : IJPR · 2016Review
- Synthesis of dihydropyrimidine α,γ-diketobutanoic acid derivatives targeting HIV integrase.European journal of medicinal chemistry · 2015Article
- Integrase Inhibitor Prodrugs: Approaches to Enhancing the Anti-HIV Activity of β-Diketo Acids.Molecules (Basel, Switzerland) · 2015Review
- A novel molecule with notable activity against multi-drug resistant tuberculosis.Bioorganic & medicinal chemistry letters · 2015Article
- Pharmacokinetics and dose-range finding toxicity of a novel anti-HIV active integrase inhibitor.Antiviral research · 2014Article
- Notable difference in anti-HIV activity of integrase inhibitors as a consequence of geometric and enantiomeric configurations.Bioorganic & medicinal chemistry letters · 2013Article
- A novel anti-HIV active integrase inhibitor with a favorable in vitro cytochrome P450 and uridine 5'-diphospho-glucuronosyltransferase metabolism profile.Antiviral research · 2013Article
- Solid-state tautomeric structure and invariom refinement of a novel and potent HIV integrase inhibitor.Acta crystallographica. Section C, Crystal structure communications · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Worldwide research efforts in drug discovery involving HIV integrase have produced only one compound, raltegravir, that has been approved for clinical use in HIV/AIDS. As resistance, toxicity and drug-drug interactions are recurring issues with all classes of anti-HIV drugs, the discovery of novel integrase inhibitors remains a significant scientific challenge. We have designed a lead HIV-1 strand transfer (ST) inhibitor (IC(50) 70 nM), strategically assembled on a pyridinone scaffold. A focused structure-activity investigation of this parent compound led to a significantly more potent ST inhibitor, 2 (IC(50) 6 ± 3 nM). Compound 2 exhibits good stability in pooled human liver microsomes. It also displays a notably favorable profile with respect to key human cytochrome P450 (CYP) isozymes and human UDP glucuronosyl transferases (UGTs). The prodrug of inhibitor 2, i.e., compound 10, was found to possess remarkable anti-HIV-1 activity in cell culture (EC(50) 9 ± 4 nM, CC(50) 135 ± 7 μM, therapeutic index = 15,000).
Identifiers
What OpenQuestion holds
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.