Design and synthesis of novel rofecoxib analogs as potential cyclooxygenase (COX‐2) inhibitors: Replacement of the methylsulfonyl pharmacophore by a sulfonylazide bioisostere
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
Abstract A group of rofecoxib analogs, having a sulfonylazide (SO 2 N 3 ) substituent in place of the methanesulfonyl (SO 2 CH 3 ) pharmacophore at the meta ‐position viz 3‐(4‐methyl, 4‐methoxy, or 4‐ethoxyphenyl)‐4‐(3‐sulfonylazidophenyl)‐2(5 H )furanone ( 7a‐c ) and para ‐position viz 3‐phenyl‐4‐(4‐sulfonylazidophenyl)‐2(5 H )furanone ( 7d ), 3‐(4‐fluoro, or 4‐chlorophenyl)‐4‐(4‐sulfonylazidophenyl)‐2(5 H )furanone ( 7e‐f ) of the C–4 phenyl ring, and 4‐(1‐oxido‐4‐pyridyl)‐3‐phenyl‐2(5 H )furanone ( 12 ) were designed and synthesized for evaluation as selective cyclooxygenase‐2 (COX‐2) inhibitors. In vitro COX‐1/COX‐2 enzyme inhibition studies showed that 3‐phenyl‐4‐(4‐sulfonylazidophenyl)‐2(5 H )furanone ( 7d ) inhibited COX‐1 selectively (COX‐1 IC 50 = 0.6659 μM; COX‐2 IC 50 > 100 μM) and 3‐(4‐fluorophenyl)‐4‐(4‐sulfonylazidophenyl)‐2(5 H )furanone ( 7e ) inhibited both enzymes (COX‐1 IC 50 = 0.8494 μM; COX‐2 IC 50 = 1.7661 μM). A molecular modeling study was performed where 3‐(4‐fluorophenyl)‐4‐(4‐sulfonylazidophenyl)‐2(5 H )furanone ( 7e ) was docked in the active site of murine COX‐2 isozyme, which showed that the sulfonylazido group inserts deep into the 2°‐pocket of COX‐2 where it undergoes both H ‐bonding (Gln 192 , Phe 518 ) and weak electrostatic (Arg 513 ) interactions.
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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 | 0.001 | 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 it