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These compounds are derived from a planar, aromatic scaffold and functionalized with four points of diversity.
Synthetic routes were devised to allow for array synthesis in which all three points of diversity could be facilely explored.
In this study, four points of diversity within a dibenzo-epine scaffold were varied systematically and the pharmacologic profiles of the compounds were assessed across 14 receptors and transporters thought to be important to clinical profiles of efficacy and safety.
The multiple points of diversity embodied in the heterocyclic scaffold render it well-suited to the exploration of the S′ subsites of Pr 3. Molecular modeling studies suggest that further exploration of the S′ subsites of Pr 3 using the aforementioned heterocyclic scaffold may lead to the identification of highly selective, reversible competitive inhibitors of Pr 3.
Preliminary work suggests that these points of diversity have very important implications.
In total, 22 unactivated α,β-unsaturated esters substrates with three points of diversity successfully cyclized under the action of catalyst 4 k to give the bicyclic products with the morphan skeleton in high diastereo- and enantioselectivity.
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Beyond these points the level of diversity starts to decrease with increasing R0.
"But the point of diversity and gender balance is that it gets the best outcome.
Since targets 4 and 5 differ only in their acyl chain substitution, we elected to pursue a synthetic strategy that would allow the introduction of this point of diversity in the final step.
Initially, substrate 2 a was chosen as a model system to test our concept; its precursor 1 was accessible on scale, 7 the spirocyclic pyrrolidinone backbone would place reactive functionality in close proximity, 8 and its synthesis by cross metathesis would provide a point of diversity if the desymmetrization proved successful.
It's ranked 13th on environment, losing points for lack of diversity and being ranked at 19 by the World Economic Forum.
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