The design and synthesis of novel bioisosteric analogues of triptorelin acetate containing tetrazole moiety at C‐ or N‐terminus of the peptides is described. Tetrazole acetic acid was synthesized through the reaction of an alkyl cyanoacetate and sodium azide, after that, it was coupled to the N‐terminus of triptorelin instead of pyroglutamic acid. In another approach, tetrazole acetohydrazide was prepared and conjugated to the C‐terminus of triptorelin instead of the amide bond. The synthesized peptides containing tetrazole moiety at the C‐ or N‐terminus of the peptide sequence are peptidomimetics of triptorelin acetate. The docking results of the designed derivatives showed the same interaction of triptorelin with the receptor but with a higher score.The peptide that has tetrazole moiety in its C‐terminus, restricted the testosterone level during four weeks of in vivo study and led to keep testosterone at a moderate level during the first week compared to control.

Background: Proteolysis-targeting chimera (PROTAC) is a bifunctional molecule comprising a ligand to recognize the targeted protein to be degraded. Objectives: To use the advantages of the PROTAC technique, we have synthesized novel compounds to degrade inosine monophosphate dehydrogenase (IMPDH) by the proteasome system. Methods: We describe the synthesis of new PROTACs based on a combination of mycophenolic acid (MPA) as the potent IMPDH inhibitor and pomalidomide as a ligand of E3 ubiquitin ligase via linkers formed from Cu(I)-catalyzed cycloaddition reaction. Results: All synthesized compounds were investigated against Jurkat cells as acute T-cell leukemia and were potent apoptosis inducers at 50 nM. Conclusion: The effect of compound 2 in 0.05 μM on IMPDH degradation can be almost prevented by competition with bortezomib as the proteasome inhibitor at 0.1 and 0.5 μM.