Evidence map›Paper›PMID 27769620›Full record

ArticleBioorganic & medicinal chemistry letters2016

Synthesis and biological evaluation of ranitidine analogs as multiple-target-directed cognitive enhancers for the treatment of Alzheimer's disease.

Jie Gao, Narasimha Midde, Jun Zhu, Alvin V Terry, Campbell McInnes, James M Chapman

Open access · greenAbstract read
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.5field-weighted citation impact, top 16% 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

3 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
  3. 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

6 authors at 2 institutions in 1 country.

Jie GaoDrug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA; Department of Pharmacology and Toxicology, Augusta University, Health Sciences Campus, CB-3530, 1459 Laney Walker Blvd., Augusta, GA 30912, USA.
Narasimha MiddeDrug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA.
Jun ZhuDrug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA.
Alvin V TerryDepartment of Pharmacology and Toxicology, Augusta University, Health Sciences Campus, CB-3530, 1459 Laney Walker Blvd., Augusta, GA 30912, USA.
Campbell McInnesDrug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA. Electronic address: mcinnes@sccp.sc.edu.
James M ChapmanDrug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA.
University of South Carolina · USAugusta University Health · US

Funding

Molecular mechanisms: Dysregulation of monoamine transporters by HIV-1Tat and cocaineR01DA035714 · NIDA · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI Jay P. McLaughlin, CHANG-GUO ZHAN · 2013 to 2026
$6.6M
NIDA NIH HHS R01 DA035714
6 · The paper itself

Abstract

Using molecular modeling and rationally designed structural modifications, the multi-target structure-activity relationship for a series of ranitidine analogs has been investigated. Incorporation of a variety of isosteric groups indicated that appropriate aromatic moieties provide optimal interactions with the hydrophobic and π-π interactions with the peripheral anionic site of the AChE active site. The SAR of a series of cyclic imides demonstrated that AChE inhibition is increased by additional aromatic rings, where 1,8-naphthalimide derivatives were the most potent analogs and other key determinants were revealed. In addition to improving AChE activity and chemical stability, structural modifications allowed determination of binding affinities and selectivities for M1-M4 receptors and butyrylcholinesterase (BuChE). These results as a whole indicate that the 4-nitropyridazine moiety of the JWS-USC-75IX parent ranitidine compound (JWS) can be replaced with other chemotypes while retaining effective AChE inhibition. These studies allowed investigation into multitargeted binding to key receptors and warrant further investigation into 1,8-naphthalimide ranitidine derivatives for the treatment of Alzheimer's disease.

Indexed as

AcetylcholinesteraseAlzheimer DiseaseAnimalsButyrylcholinesteraseCholinesterase InhibitorsHumansMiceModels, MolecularNaphthalimidesNootropic AgentsRanitidineReceptor, Muscarinic M1Receptor, Muscarinic M4Structure-Activity RelationshipAcetylcholinesteraseButyrylcholinesteraseCholinesterase InhibitorsNaphthalimidesNootropic AgentsRanitidineReceptor, Muscarinic M1Receptor, Muscarinic M4AcetylcholinesteraseAlzheimers DiseaseMulti-targetRanitidine

Identifiers

PMID27769620
PMCPMC5185470
OpenAlexW2529515860

What OpenQuestion holds

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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.