Synthesis and Nucleotide Pyrophosphatase/Phosphodiesterase Inhibition Studies of Carbohydrazides Based on Benzimidazole‐Benzothiazine Skeleton
Bibliographic record
Abstract
Abstract Ecto‐nucleotide pyrophosphatases/phosphodiesterases (ENPPs) are important family of ecto‐nucleotidases. There are seven members of ENPP family out of which ENPP1 and ENPP3 hydrolyze nucleotides whereas, ENPP2 preferably hydrolyzes phospholipids as compared to nucleotides. Overexpression of ENPP1 and ENPP3 has been reported to be associated with many health disorders such as diabetes, chondrocalcinosis, osteoarthritis, and cancer. Development of ENPP1 and −3 inhibitors might be useful for the treatment of these disorders. This study aimed to investigate the inhibitory potentials of the synthesized benzimidazole‐benzothiazine hybrid molecules on ecto‐nucleotide pyrophosphatases/phosphodiesterases (ENPPs) enzymes. A series of benzimidazole‐benzothiazine hybrid molecules was synthesized by Gabriel–Colman rearrangement of methyl 2‐(1,1‐dioxido‐3‐oxobenzo[ d ]isothiazol‐2(3 H )‐yl)acetate. The successfully synthesized compounds ( 6 a – 6 m ) were evaluated for ENPP1 and −3 inhibitory activities. Among the investigated compounds 6 m with an IC 50 value of 0.14 μ M, and 6 h with an IC 50 value of 0.12 μ M, were found to be the most potent inhibitors of ENPP1 and −3, respectively. Molecular docking studies of most active and selective inhibitors showed putative mode of binding interactions responsible for highest potency and selectivity of docked inhibitors. The overall in‐silico results were found to be highly correlated with in‐vitro results showed in Table 1.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.000 |
| 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".