ArticleJournal of medicinal chemistry2016
Hit-to-Lead Studies for the Antimalarial Tetrahydroisoquinolone Carboxanilides.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 56 citations in OpenAlex.
- Stereodivergent Synthesis of ComplexOrganic letters · 2025Article
- Antimalarial Drug Discovery from Natural and Synthetic Sources.Current medicinal chemistry · 2025Review
- Optimization of diastereomeric dihydropyridines as antimalarials.European journal of medicinal chemistry · 2024Article
- The Castagnoli-Cushman Reaction.Molecules (Basel, Switzerland) · 2023Review
- Novel Tetrahydroisoquinoline-Based Heterocyclic Compounds Efficiently Inhibit SARS-CoV-2 InfectionViruses · 2023Article
- Synthesis of Novel 1-Oxo-2,3,4-trisubstituted Tetrahydroisoquinoline Derivatives, Bearing Other Heterocyclic Moieties and Comparative Preliminary Study of Anti-Coronavirus Activity of Selected Compounds.Molecules (Basel, Switzerland) · 2023Article
- Extending the Scope of the New Variant of the Castagnoli-Cushman Cyclocondensation ontoMolecules (Basel, Switzerland) · 2022Article
- Trifluoroethanol Promoted Castagnoli-Cushman Cycloadditions of Imines with Homophthalic Anhydride.Molecules (Basel, Switzerland) · 2022Article
- Stereoelectronic Features of a Complex Ketene Dimerization Reaction.Molecules (Basel, Switzerland) · 2021Article
- A Novel Dual Organocatalyst for the Asymmetric Pinder Reaction and a Mechanistic Proposal Consistent with the Isoinversion Effect Thereof.Molecules (Basel, Switzerland) · 2021Article
- Medicinal chemistry perspectives of 1,2,3,4-tetrahydroisoquinoline analogs - biological activities and SAR studies.RSC advances · 2021Review
- Selecting an anti-malarial clinical candidate from two potent dihydroisoquinolones.Malaria journal · 2021Article
- In vitro Multistage Malaria Transmission Blocking Activity of Selected Malaria Box Compounds.Drug design, development and therapy · 2020Article
- Synthesis of DNA-coupled isoquinolones and pyrrolidines by solid phase ytterbium- and silver-mediated imine chemistry.MedChemComm · 2019Article
- The past, present and future of anti-malarial medicines.Malaria journal · 2019Review
- Facile Access to Fe(III)-Complexing Cyclic Hydroxamic Acids in a Three-Component Format.Molecules (Basel, Switzerland) · 2019Article
- Formal [4 + 2] cycloaddition of imines with alkoxyisocoumarins.Organic & biomolecular chemistry · 2018Article
- Stereochemistry and Reactivity of the HPA-Imine Mannich Intermediate.Tetrahedron letters · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Phenotypic whole-cell screening in erythrocytic cocultures of Plasmodium falciparum identified a series of dihydroisoquinolones that possessed potent antimalarial activity against multiple resistant strains of P. falciparum in vitro and show no cytotoxicity to mammalian cells. Systematic structure-activity studies revealed relationships between potency and modifications at N-2, C-3, and C-4. Careful structure-property relationship studies, coupled with studies of metabolism, addressed the poor aqueous solubility and metabolic vulnerability, as well as potential toxicological effects, inherent in the more potent primary screening hits such as 10b. Analogues 13h and 13i, with structural modifications at each site, were shown to possess excellent antimalarial activity in vivo. The (+)-(3S,4S) enantiomer of 13i and similar analogues were identified as the more potent. On the basis of these studies, we have selected (+)-13i for further study as a preclinical candidate.
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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.