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Record W2512968948 · doi:10.1111/cbdd.12846

1‐[(Imidazolidin‐2‐yl)imino]‐1<i>H</i>‐indoles as new hypotensive agents: synthesis and<i>in vitro</i>and<i>in vivo</i>biological studies

2016· article· en· W2512968948 on OpenAlexaff
Anita Kornicka, Aleksandra Wasilewska, Jarosław Sączewski, Alan L. Hudson, Konrad Boblewski, Artur Lehmann, Karol Gzella, Mariusz Belka, Franciszek Sączewski, М. Gdaniec, Apolonia Rybczyńska, Tomasz Bączek

Bibliographic record

VenueChemical Biology & Drug Design · 2016
Typearticle
Languageen
FieldChemistry
TopicChemical Reaction Mechanisms
Canadian institutionsUniversity of Alberta
Fundersnot available
KeywordsIn vivoIn vitroPharmacologyChemistryStereochemistryCombinatorial chemistryBiochemistryMedicineBiology

Abstract

fetched live from OpenAlex

A series of 1‐[(imidazolidin‐2‐yl)imino]‐1 H ‐indole analogues of hypotensive α 2 ‐AR agonists, 1‐[(imidazolidin‐2‐yl)imino]‐1 H ‐indazoles, was synthesized and tested in vitro for their activities at α 1 ‐ and α 2 ‐adrenoceptors as well as imidazoline I 1 and I 2 receptors. The most active 1‐[(imidazolidin‐2‐yl)imino]‐1 H ‐indoles displayed high or moderate affinities for α 1 ‐ and α 2 ‐adrenoceptors and substantial selectivity for α 2 ‐adrenoceptors over imidazoline‐I 1 binding sites. The in vivo cardiovascular properties of indole derivatives 3 revealed that substitution at C‐7 position of the indole ring may result in compounds with high cardiovascular activity. Among them, 7‐fluoro congener 3g showed the most pronounced hypotensive and bradycardic activities in this experiment at a dose as low as 10 μg/kg i.v. Metabolic stability of the selected compounds of type 3 was determined using both in vitro and in silico approaches. The results indicated that these compounds are not vulnerable to rapid first‐phase oxidative metabolism.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.006
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.013
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.006
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.053
GPT teacher head0.281
Teacher spread0.228 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations8
Published2016
Admission routes1
Has abstractyes

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