Sulfonamide-Based Acyclic and Conformationally Constrained MMP Inhibitors: From Computer-Assisted Design to Nanomolar Compounds
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
The present account relates to our studies in the computer assisted design and synthesis of acyclic and cyclic MMP inhibitors. Our early efforts focused on the preparation of cyclopropane and tetrahydrofuran-based mimics of batimastat which were not active. The discovery of subnanomolar sulfonamide-based acyclic inhibitors instigated the design of novel target compounds. Thus, with the help of a fully automated and reliable docking program, we embarked on the design and synthesis of enantiopure inhibitors incorporating cyclic scaffolds. This ultimately led to compounds exhibiting inhibitory activities in the nanomolar range. Interestingly, the qualitative ranking prediction was found to be in good agreement with the observed activities.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| 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