Acyclic triaryl olefins possessing a sulfohydroxamic acid pharmacophore: synthesis, nitric oxide/nitroxyl release, cyclooxygenase inhibition, and anti-inflammatory studies
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Nitric oxide (NO) and its reduced form nitroxyl (HNO), effective vasodilation agents that can inhibit platelet aggregation and adhesion, could suppress adverse cardiovascular effects associated with the use of selective COX-2 inhibitors. In this regard, a sulfohydroxamic acid (SO(2)NHOH) substituent, that can act as a dual NO/HNO donor moiety, was inserted at the para-position of the C2 phenyl ring of acyclic 2-alkyl-1,1,2-triaryl olefins previously shown to be potent and highly selective COX-2 inhibitors. Although this new group of 1,1-diaryl-2-(4-hydroxyaminosulfonylphenyl)alk-1-enes exhibited weak inhibition of the constitutive cyclooxygenase-1 (COX-1) and inducible COX-2 isozymes, in vivo studies showed anti-inflammatory potencies that were generally intermediate between that of the reference drugs aspirin and ibuprofen. All compounds released NO (5.6-13.5% range) upon incubation with phosphate buffer which was increased further (8.3-25.6% range) in the presence of the oxidant K(3)(FeCN(6)).The low release of HNO in MeOH-buffer (< 2% at 24 h incubation) was much higher at alkaline pH (11-37% range). The concept of designing better anti-inflammatory drugs possessing either an effective HNO, or dual NO/HNO, donor moiety that are devoid of adverse ulcerogenic and/or cardiovascular side effects warrants further investigation.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 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) | 0.001 | 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 it