Evidence map›Paper›PMID 27364611›Full record

ArticleBioorganic & medicinal chemistry2016

Design, synthesis, and pharmacological evaluation of JDTic analogs to examine the significance of replacement of the 3-hydroxyphenyl group with pyridine or thiophene bioisosteres.

Chad M Kormos, Moses G Gichinga, Scott P Runyon, James B Thomas, S Wayne Mascarella, Ann M Decker, Hernán A Navarro, F Ivy Carroll

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

Article in Bioorganic & medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

0 citing papers in PubMed, 6 citations in OpenAlex.

No citing paper in PubMed yet.

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

8 authors at 1 institution in 1 country.

Chad M KormosResearch Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709-2194, United States.
Moses G GichingaResearch Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709-2194, United States.
Scott P RunyonResearch Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709-2194, United States.
James B ThomasResearch Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709-2194, United States.
S Wayne MascarellaResearch Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709-2194, United States.
Ann M DeckerResearch Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709-2194, United States.
Hernán A NavarroResearch Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709-2194, United States.
F Ivy CarrollResearch Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709-2194, United States. Electronic address: fic@rti.org.
RTI International · US

Funding

Selective Opioid Antagonists as Medications for Drug AbuseR01DA009045 · NIDA · RESEARCH TRIANGLE INSTITUTE · PI CARROLL, FRANK IVY · 1994 to 2014
$5.6M
NIDA NIH HHS R01 DA009045
6 · The paper itself

Abstract

The potent and selective KOR antagonist JDTic was derived from the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine class of pure opioid antagonists. In previous studies we reported that compounds that did not have a hydroxyl on the 3-hydroxyphenyl group and did not have methyl groups at the 3- and 4-position of the piperidine ring were still potent and selective KOR antagonists. In this study we report JDTic analogs 2, 3a-b, 4a-b, and 5, where the 3-hydroxyphenyl ring has been replaced by a 2-, 3-, or 4-pyridyl or 3-thienyl group and do not have the 3-methyl or 3,4-dimethyl groups, remain potent and selective KOR antagonists. Of these, (3R)-7-hydroxy-N-(1S)-2-methyl-[4-methyl-4-pyridine-3-yl-carboxamide (3b) had the best overall binding potency and selectivity in a [(35)S]GTPγS functional assay, with a Ke=0.18nM at the KOR and 273- and 16,700-fold selectivity for the KOR relative to the MOR and DOR, respectively. Calculated physiochemical properties for 3b suggest that it will cross the blood-brain barrier.

Indexed as

Drug DesignBlood-Brain BarrierPiperidinesPyridinesSpectrum AnalysisTetrahydroisoquinolinesThiophenes7-hydroxy-N-(1-((4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl)methyl)-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamidePiperidinesPyridinesTetrahydroisoquinolinesThiophenesADME propertiesJDTicKappa antagonistOpioids

Identifiers

PMID27364611
PMCPMC4957640
OpenAlexW2426542253

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.