Evidence map›Paper›PMID 34098081›Full record

ArticleBioorganic & medicinal chemistry letters2021

Synthesis and biological activity of conformationally restricted indole-based inhibitors of neurotropic alphavirus replication: Generation of a three-dimensional pharmacophore.

Scott J Barraza, Janice A Sindac, Craig J Dobry, Philip C Delekta, Pil H Lee, David J Miller, Scott D Larsen

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.8field-weighted citation impact, top 26% of its field
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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Review
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

7 authors at 1 institution in 1 country.

Scott J BarrazaDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, United States.
Janice A SindacDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, United States.
Craig J DobryDepartments of Internal Medicine and Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, United States.
Philip C DelektaDepartments of Internal Medicine and Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, United States.
Pil H LeeVahlteich Medicinal Chemistry Core, University of Michigan, Ann Arbor, MI 48109, United States; Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, United States.
David J MillerDepartments of Internal Medicine and Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, United States.
Scott D LarsenVahlteich Medicinal Chemistry Core, University of Michigan, Ann Arbor, MI 48109, United States; Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, United States. Electronic address: sdlarsen@med.umich.edu.
University of Michigan–Ann Arbor · US

Funding

Novel Therapeutics for Neurotropic AlphavirusesR01AI089417 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MILLER, DAVID J · 2010 to 2014
$4.5M
NIAID NIH HHS R01 AI089417
6 · The paper itself

Abstract

We have previously reported the development of indole-based CNS-active antivirals for the treatment of neurotropic alphavirus infection, but further optimization is impeded by a lack of knowledge of the molecular target and binding site. Herein we describe the design, synthesis and evaluation of a series of conformationally restricted analogues with the dual objectives of improving potency/selectivity and identifying the most bioactive conformation. Although this campaign was only modestly successful at improving potency, the sharply defined SAR of the rigid analogs enabled the definition of a three-dimensional pharmacophore, which we believe will be of value in further analog design and virtual screening for alternative antiviral leads.

Indexed as

AlphavirusAntiviral AgentsDose-Response Relationship, DrugDrug DesignIndolesMicrobial Sensitivity TestsMolecular ConformationStructure-Activity RelationshipVirus ReplicationAntiviral AgentsIndolesAntiviralConformationally restrictedNeurotropic alphavirusPharmacophoreWestern equine encephalitis virus

Identifiers

PMID34098081
PMCPMC8272561
OpenAlexW3166747996

What OpenQuestion holds

Textmetadata
LicenceTDM
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.