Cyclic Enkephalins with a Diversely Substituted Guanidine Bridge or a Thiourea Bridge: Synthesis, Biological and Structural Evaluations
Bibliographic record
Abstract
Two series of 22 and 15 atom cyclic enkephalins incorporating a diversely substituted guanidine bridge have been prepared to assess the potential effect of the bridge substitutions on their opioid activity profile. The most notable results were obtained with the shortest cyclic analogues, which showed a significant variation of their binding affinity toward μ and δ opioid receptors in relation to bridge substitution. NMR studies were performed to rationalize these data. Some small analogues were found to exist as at least one major and one minor stable forms, which could be separated by chromatography. In particular, the compounds 13 and 14 with a cyclic substituent were separated in three isomers and the basis of this multiplicity was explored by 2D NMR spectroscopy. All compounds were agonists with slight selectivity for the μ opioid receptor. Compounds 7a (thiourea bridge) and 10a (N-Me-guanidine bridge) showed nanomolar affinity toward μ receptor, the latter being the more selective for this receptor (40-fold).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| 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 | 0.000 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), 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".