Recent patents of dipeptidyl peptidase IV inhibitors

Abstract

Research in finding new DPP IV inhibitors is intense, despite the number of reported molecules. This is mainly because marketed compounds have been approved in the last 5 years and long-term side effects have not been detected. The perfect inhibitor for the T2DM treatment would therefore be a molecule that inhibits GLP-1 and GIP degradation by DPP IV, but does not affect the activity of the protease in other substrates, nor disturbs the communication of DPP IV with other proteins.

Activity and selectivity cliffs for DPP‐IV inhibitors: Lessons we can learn from SAR studies and their application to virtual screening

“…The DPP‐IV binding site is highly druggable in the sense that tight and specific binding to the enzyme can be achieved using small molecules that have drug‐like physicochemical properties . It is accessible in two ways: (1) via an opening in the β‐propeller domain, and (2) via the large side opening, which is formed at the interface of the β‐propeller and the α/β‐hydrolase domain (see Figure . The structural features of DPP‐IV suggest that substrates and inhibitors enter or leave the binding site via the side opening.…”

DPP4-directed therapeutic strategies for MERS-CoV

“…Studies have provided new insights into DPP4 interaction with substrates and inhibitors, and numerous inhibitors with varying selectivity have been characterised in DPP4 binding and functional assays. 4 Additionally, on the basis of our work on the use of DPP4 inhibitors as a treatment for autoimmune disease, DPP4 inhibition could suppress the damaging aspects of the body's own antiviral immune response by modulating infl ammation. 3 Reversible inhibitors of DPP4 enzymatic activity suppress T-cell pro liferation and production of pro infl ammatory cytokines as well as interleukin 10.…”

DPP-4 inhibitors: a patent review (2012 – 2014)

“…A mixture of Leu-HypGly, Ile-Hyp-Gly, Ala-Hyp-Gly, Ser-Hyp-Gly, Glu-HypGly, Ala-Pro-Gly, Leu-Pro-Gly, and so on were obtained and tested. IC 50 values of Leu-Hyp-Gly (29) and Ala-ProGly (30) against DPP-4 were 0.039 and 0.008 mg/ml, respectively.…”

“…Non-peptidomimetics have been divided into: pyrimidine and pyridine derivatives; 1.0 [100] catalogued the patents into two main groups; the first contains new chemical entities, organic syntheses and crystallization procedures, whereas the second group summarizes the use of DPP-4 inhibitors in preparation or associations with other molecules. All the patents that belong to the first group have been then classified following the chemical nomenclature adopted in other relevant reviews present in the literature on this topic [26][27][28][29]. The biological functions and the therapeutic [101] Inflammatory diseases DPP-4 has a role in the degradation of stromal-cellderived factor-1, TNFa and many other inflammatory molecules associated with rheumatic diseases [101].…”