Discovery of aminoheterocycles as potent and brain penetrant prolylcarboxypeptidase inhibitors
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Cited by (5)
Pyrazoles as non-classical bioisosteres in prolylcarboxypeptidase (PrCP) inhibitors
2014, Bioorganic and Medicinal Chemistry LettersProlyl carboxypeptidase and its inhibitors in metabolism
2013, Trends in Endocrinology and MetabolismCitation Excerpt :In addition, tissue permeability, specifically the penetration of PRCP inhibitors into the CNS, has also been considered. As a result, several chemical compounds have been synthesized as novel candidates for brain-permeable PRCP inhibitors [56–59]. First, compounds were produced by replacing the dichlorobenzimidazole-substituted pyrrolidine with a series of substituted benzylamines.
Validation of a specific prolylcarboxypeptidase activity assay and its suitability for plasma and serum measurements
2013, Analytical BiochemistryCitation Excerpt :Moreover, some of them are labor-intensive and time-consuming or are hampered by interferences, whereas others require a special permit to use materials such as radiolabeled substrates. Furthermore, a fluorometric assay that uses Mca-Ala-Lys(Dnp)-OH as its substrate, which tends to bind to plasma proteins, has been reported, thereby making it impossible to measure PRCP activity in serum or plasma samples [22,59]. In addition, the standard deviation of the method was described as generally less than 50%, a performance level that does not achieve clinical applicability and is high compared with that of our in-house methods (<10%) [60].
Discovery and development of prolylcarboxypeptidase inhibitors for cardiometabolic disorders
2013, Annual Reports in Medicinal ChemistryCitation Excerpt :Additionally, these were active in the whole plasma mAngIII assay, while displaying reduced Pgp efflux potential. Compound 8 (hPRPC IC50 = 43 nM; mAngIII IC50 = 350 nM) was selected and further evaluated in CF1 and WT mice (SC administration); a brain/plasma ratio of 1.4 was achieved, representing a strong effort in creating CNS-active PRCP inhibitors.39 Benzodihydroisofuran scaffolds were elaborated to produce CNS-penetrating PRCP inhibitors represented by ent-9 (hPRCP IC50 = 0.44 nM; mAngIII IC50 = 23 nM).
Prolylcarboxypeptidase (PrCP) inhibitors and the therapeutic uses thereof: a patent review
2017, Expert Opinion on Therapeutic Patents