Novel imidazo[1,2-a][1,8]naphthyridine derivatives and their preliminary in vitro assays for the evaluation as positive inotropes
Bibliographic record
Abstract
N Heterocycles present in over 50 % of the US Food and Drug Administration (FDA) approved small-molecule drugs, are of great interest to medicinal chemists to date. Six novel compounds ( S5 - S10 ) with such fused N -heterocyclic system namely imidazo[1,2- a ][1,8]naphthyridine, derived from imidazole and 1,8-naphthyridine scaffolds, have been synthesized in this study. Following the three-step reaction scheme, these six compounds were further characterized using spectroscopic techniques including 1 H NMR, 13 C NMR, and LCMS; prior to evaluation of their aqueous kinetic solubilities. Molecular docking studies were performed using Na + /K + -ATPase and PDE3B enzymes to evaluate their potential for positive inotropy. It was found that compounds S5 - S10 had more potential to bind with the PDE3B enzyme than Na + /K + -ATPase, among which S6 and S8 had the best binding affinities and interactions with the former. This trend was correlated to in vitro activity in H9c2(2–1) cardiomyoblasts as the compounds failed to inhibit Na + /K + -ATPase significantly, while S5, S9 , and S10 preliminarily indicated PDE3 inhibition via increasing intracellular cAMP concentrations. Among these three compounds, compound S9 further demonstrated cell viability (IC 50 >100 µM) that was comparable to the marketed positive inotrope digoxin , and was predicted as a weak/moderate hERG channel blocker .
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".