Evidence map›Paper›PMID 27318976›Full record

ArticleEuropean journal of medicinal chemistry2016

Synthesis and biological evaluation of indole-2-carboxamides bearing photoactivatable functionalities as novel allosteric modulators for the cannabinoid CB1 receptor.

Chang-Jiang Qiao, Hamed I Ali, Kwang H Ahn, Srikanth Kolluru, Debra A Kendall, Dai Lu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European 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 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
–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

14 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Allosteric modulators restore orthosteric agonist binding to mutated CBThe Journal of pharmacy and pharmacology · 2020
    Article
  4. Article
  5. Review
  6. Review
  7. Discovery of Selective Cannabinoid CBSLAS discovery : advancing life sciences R & D · 2018
    Article
  8. Review
  9. Preclinical Studies of Cannabinoid Reward, Treatments for Cannabis Use Disorder, and Addiction-Related Effects of Cannabinoid Exposure.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018
    Review
  10. Article
  11. Review
  12. Review
  13. Assessing Allosteric Modulation of CBMethods in enzymology · 2017
    Article
  14. 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

6 authors.

Chang-Jiang QiaoIrma Lerma Rangel College of Pharmacy, Health Science Center, Texas A&M University, 1010 West Avenue B, Kingsville, TX 78363, United States; School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
Hamed I AliIrma Lerma Rangel College of Pharmacy, Health Science Center, Texas A&M University, 1010 West Avenue B, Kingsville, TX 78363, United States.
Kwang H AhnDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, United States.
Srikanth KolluruIrma Lerma Rangel College of Pharmacy, Health Science Center, Texas A&M University, 1010 West Avenue B, Kingsville, TX 78363, United States.
Debra A KendallDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, United States. Electronic address: debra.kendall@uconn.edu.
Dai LuIrma Lerma Rangel College of Pharmacy, Health Science Center, Texas A&M University, 1010 West Avenue B, Kingsville, TX 78363, United States. Electronic address: dlu@tamhsc.edu.

Funding

CB1 Allosteric Modulators: Molecular, Cellular and In Vivo PharmacologyR01DA039942 · NIDA · UNIVERSITY OF CONNECTICUT STORRS · PI KINSEY, STEVEN G., LICHTMAN, ARON H · 2016 to 2020
$2.6M
NIDA NIH HHS R01 DA039942
6 · The paper itself

Abstract

5-Chloro-3-ethyl-N-(4-(piperidin-1-yl)phenethyl)-1H-indole-2-carboxamide (ORG27569, 1) is a prototypical allosteric modulator for the cannabinoid CB1 receptor. Based on this indole-2-carboxamide scaffold, we designed and synthesized novel CB1 allosteric modulators that possess photoactivatable functionalities, which include benzophenone, phenyl azide, aliphatic azide and phenyltrifluoromethyldiazrine. To assess their allosteric effects, the dissociation constant (KB) and allosteric binding cooperativity factor (α) were determined and compared to their parent compounds. Within this series, benzophenone-containing compounds 26 and 27, phenylazide-containing compound 28, and the aliphatic azide containing compound 36b showed allosteric binding parameters (KB and α) comparable to their parent compound 1, 7, 8, and 9, respectively. We further assessed these modulators for their impact on G-protein coupling activity. Interestingly, these compounds exhibited negative allosteric modulator properties in a manner similar to their parent compounds, which antagonize agonist-induced G-protein coupling. These novel CB1 allosteric modulators, possessing photoactivatable functionalities, provide valuable tools for future photo-affinity labeling and mapping the CB1 allosteric binding site(s).

Indexed as

LightAllosteric RegulationChemistry Techniques, SyntheticHEK293 CellsHumansIndolesReceptor, Cannabinoid, CB1IndolesReceptor, Cannabinoid, CB1Allosteric modulatorCannabinoid receptorPhotoactivatable ligandsPhotoaffinity labeling

Identifiers

PMID27318976
PMCPMC4987248

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.