Synthesis of alkyl 6‐methyl‐4‐(2‐trifluoromethylphenyl)‐1,2,3,4‐tetrahydro‐2<i>H</i>‐pyrimidine‐2‐one‐5‐carboxylates possessing a N‐3 nitro substituent to determine calcium channel modulation structure‐activity relationships
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 magnified image The Bigenelli acid catalyzed condensation of 2‐trifluoromethylbenzaldehyde ( 1 ), urea ( 2 ) and an alkyl acetoacetate ( 3 ) afforded the respective alkyl (Me, Et, i ‐Pr, i ‐Bu) 6‐methyl‐4‐(2‐trifluoromethylphenyl)‐1,2,3,4‐tetrahydro‐2 H ‐pyrimidine‐2‐one‐5‐carboxylate ( 4‐7 ). Subsequent N 3 ‐nitration of the alkyl esters ( 4‐7 ) using Cu(NO 3 ) 2 3H 2 O and Ac 2 O furnished the target alkyl 6‐methyl‐3‐nitro‐4‐(2‐trifluoromethylphenyl)‐1,2,3,4‐tetrahydro‐2 H ‐pyrimidine‐2‐one‐5‐carboxylates ( 8‐11 ). The N 3 ‐nitro compounds ( 8‐11 ) were less potent calcium channel antagonists (IC 50 values in the 1.9 × 10 −7 to 3.9 × 10 −6 M range) on guinea pig ileal longitudinal smooth muscle than the reference drug nifedipine (Adalat®, IC 50 = 1.4 × 10 −8 M). In vitro calcium channel modulation studies on guinea pig left atrium (GPLA) showed that the methyl and ethyl esters ( 8‐9 ) induced a weak‐to‐modest positive inotropic (agonist) effect, and that the inactive isopropyl ( 10 ) and isobutyl ( 11 ) esters did not alter the cardiac contractile force of GPLA.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 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 it