628318-91-2Relevant articles and documents
Synthesis and Evaluation of Macrocyclic Transition State Analogue Inhibitors for α-Chymotrypsin
Hansen, Kristina K.,Grosch, Benjamin,Greiveldinger-Poenaru, Sorana,Bartlett, Paul A.
, p. 8465 - 8470 (2007/10/03)
Lactams 1 and 2 are readily formed from acyclic precursors in the presence of trypsin and chymotrypsin, respectively, identifying the macrocyclic ring system as a potential motif for constrained transition state analogue inhibitors of the serine peptidases. Ketone 3 was synthesized and shown to be a modest inhibitor of chymotrypsin (Ki = 220 μM), albeit 4-fold more potent than the acyclic hydroxy acid 25 (Ki = 1.5 mM as a mixture of epimers). A precursor (31) to the amino boronic acid 4 was also prepared; although this derivative was a potent inhibitor of chymotrypsin (Ki = 130 nM) by virtue of the boronic acid moiety, it showed no advantage over the des-amino analogue 32 (Ki = 120 nM), which is not capable of cyclizing.