Evidence map›Paper›PMID 33979164›Full record

ArticleJournal of medicinal chemistry2021

Aminoalkoxycarbonyloxymethyl Ether Prodrugs with a pH-Triggered Release Mechanism: A Case Study Improving the Solubility, Bioavailability, and Efficacy of Antimalarial 4(1

Andrii Monastyrskyi, Fabian Brockmeyer, Alexis N LaCrue, Yingzhao Zhao, Steven P Maher, Jordany R Maignan, Vivian Padin-Irizarry, Yana I Sakhno, Prakash T Parvatkar, Ami H Asakawa and 5 more

Abstract read
In one paragraph

Article in Journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
  2. Optimization of diastereomeric dihydropyridines as antimalarials.European journal of medicinal chemistry · 2024
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. 7-ACS infectious diseases · 2023
    Article
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Andrii MonastyrskyiDepartment of Chemistry, University of South Florida, CHE 205, 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
Fabian BrockmeyerDepartment of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, 102 Hurtig Hall, Boston, Massachusetts 02115, United States.
Alexis N LaCrueDepartment of Global Health, College of Public Health, University of South Florida, 3720 Spectrum Blvd, Suite 304, Tampa, Florida 33612, United States.
Yingzhao ZhaoDepartment of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, 102 Hurtig Hall, Boston, Massachusetts 02115, United States.
Steven P MaherCenter for Tropical and Emerging Global Diseases, University of Georgia, Athens, Coverdell Center, Rm 370B, 500 DW Brooks Drive, Athens, Georgia 30602, United States.
Jordany R MaignanDepartment of Chemistry, University of South Florida, CHE 205, 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
Vivian Padin-IrizarryDepartment of Biology, Clayton State University, 2000 Clayton State Boulevard, Morrow, Georgia 30260, United States.
Yana I SakhnoDepartment of Chemistry, University of South Florida, CHE 205, 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
Prakash T ParvatkarDepartment of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, 102 Hurtig Hall, Boston, Massachusetts 02115, United States.
Ami H AsakawaDepartment of Pharmaceutical Sciences, Northeastern University, 102 Hurtig Hall, 360 Huntington Avenue, Boston, Massachusetts 02115, United States.
Lili HuangDepartment of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, 102 Hurtig Hall, Boston, Massachusetts 02115, United States.
Debora CasandraDepartment of Global Health, College of Public Health, University of South Florida, 3720 Spectrum Blvd, Suite 304, Tampa, Florida 33612, United States.
Sherwin MashkouriDepartment of Global Health, College of Public Health, University of South Florida, 3720 Spectrum Blvd, Suite 304, Tampa, Florida 33612, United States.
Dennis E KyleDepartment of Global Health, College of Public Health, University of South Florida, 3720 Spectrum Blvd, Suite 304, Tampa, Florida 33612, United States.
Roman ManetschDepartment of Chemistry, University of South Florida, CHE 205, 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.

Funding

Orally Bioavailable 4(1H)-Quinolones with Multi-Stage Antimalarial ActivityR01AI144464 · NIAID · NORTHEASTERN UNIVERSITY · PI KYLE, DENNIS E, MANETSCH, ROMAN · 2019 to 2023
$3.6M
Drugs targeting erythrocytic and exoerythrocytic stages of malariaR01GM097118 · NIGMS · UNIVERSITY OF SOUTH FLORIDA · PI MANETSCH, ROMAN · 2011 to 2015
$1.3M
NIAID NIH HHS R01 AI144464NIGMS NIH HHS R01 GM097118
6 · The paper itself

Abstract

Preclinical and clinical development of numerous small molecules is prevented by their poor aqueous solubility, limited absorption, and oral bioavailability. Herein, we disclose a general prodrug approach that converts promising lead compounds into aminoalkoxycarbonyloxymethyl (amino AOCOM) ether-substituted analogues that display significantly improved aqueous solubility and enhanced oral bioavailability, restoring key requirements typical for drug candidate profiles. The prodrug is completely independent of biotransformations and animal-independent because it becomes an active compound via a pH-triggered intramolecular cyclization-elimination reaction. As a proof-of-concept, the utility of this novel amino AOCOM ether prodrug approach was demonstrated on an antimalarial compound series representing a variety of antimalarial 4(1

Indexed as

Administration, OralAnimalsAntimalarialsCyclizationDisease Models, AnimalEthersFemaleHalf-LifeHydrogen-Ion ConcentrationMalariaMiceMice, Inbred BALB CPlasmodium falciparumProdrugsQuinolonesSolubilityAntimalarialsEthersProdrugsQuinolones

Identifiers

PMID33979164
PMCPMC8904075

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

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.