Kalinin, Dmitrii V. published the artcileNovel Potent Proline-Based Metalloproteinase Inhibitors: Design, (Radio)Synthesis, and First in Vivo Evaluation as Radiotracers for Positron Emission Tomography, Formula: C9H17NO2S, the main research area is proline hydroxyproline hydroxamic acid synthesis metalloproteinase inhibitor structure activity; diagnostic agent PET tumor imaging radiotracer mol docking MMP; Sonogashira coupling alkylation acylation Mitsunobu reaction aminolysis fluorination; nucleophilic substitution protection radiotracer biodistribution pharmacokinetic.
As dysregulation of matrix metalloproteinase (MMP) activity is associated with a wide range of pathophysiol. processes like cancer, atherosclerosis, and arthritis, MMPs represent a valuable target for the development of new therapeutics and diagnostic tools. We herein present the chiral pool syntheses, in vitro evaluation and SAR studies of a series of D- and L-proline- as well as of (4R)-4-hydroxy-L-proline-derived MMP inhibitors. Some of the synthesized hydroxamic acids were found to be potent MMP inhibitors with IC50 values in the nanomolar range, also demonstrating no off-target effects towards the other tested Zn2+-dependent metalloproteases (ADAMs and meprins). Utilizing the structure of the (2S,4S)-configured 4-hydroxyproline derivative (I), a selective picomolar inhibitor of MMP-13, the radiolabeled counterpart [18F] was successfully synthesized. The radiotracer’s biodistribution in mice as well as its serum stability were evaluated for accessing its potential use as a MMP-13 targeting PET imaging agent.
Journal of Medicinal Chemistry published new progress about Acylation. 220655-09-4 belongs to class thiomorpholine, name is tert-Butyl thiomorpholine-4-carboxylate, and the molecular formula is C9H17NO2S, Formula: C9H17NO2S.
Referemce:
Thiomorpholine – Wikipedia,
Thiomorpholine | C4H9NS – PubChem