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A new series of pyrrole\u20103\u2010carboximidamide derivatives was designed, synthesized, and evaluated as DPP\u20104 inhibitors. Most of the synthesized compounds exhibited favorable inhibitory activity against the DPP\u20104 enzyme, and compounds <jats:bold>5f<\/jats:bold> and <jats:bold>5g<\/jats:bold> were found to be the most potent inhibitors with IC\u2085\u2080 values of 12.19 and 23.08\u2009nM, respectively. In vivo studies in diabetic Wistar rats showed that daily administration of compound <jats:bold>5g<\/jats:bold> for 2 weeks resulted in a significant decrease in blood glucose compared with the control group. Moreover, compound <jats:bold>5g<\/jats:bold> was effective in reducing plasma glucose in an acute oral glucose tolerance test in NMRI mice. The antiglycemic effects of compound <jats:bold>5g<\/jats:bold> were comparable with standard treatment by sitagliptin, with no effect on normoglycemic rats. Both the in vitro and in vivo antidiabetic properties suggest that compound <jats:bold>5g<\/jats:bold> could be considered a promising candidate for development as an antidiabetic medication.<\/jats:p>","DOI":"10.1002\/ardp.70077","type":"journal-article","created":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T05:32:21Z","timestamp":1755322341000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Design, Synthesis and Antidiabetic Activity of Novel Pyrrole\u20103\u2010Carboximidamide Derivatives as Dipeptidyl Peptidase\u20104 Inhibitors"],"prefix":"10.1002","volume":"358","author":[{"given":"Hossein Fasihi","family":"Dastjerdi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, School of Pharmacy Shahid Beheshti University of Medical Sciences Tehran 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