Abstract
A series of (4β-substituted)-l-prolylpyrrolidine analogs lacking the electrophilic nitrile function were synthesized and their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and duration of ex vivo activity were evaluated. Structural optimization of a N-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine analog 8, which was found by high-speed analog synthesis, was carried out to improve the potency and duration of action. A representative compound 26 was evaluated to assess its effect on the plasma glucose level after the oGTT (oral glucose tolerance test) in normal rats. Structure-activity relationships (SAR) are also presented.
Original language | English |
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Pages (from-to) | 1613-1631 |
Number of pages | 19 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 16 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2008 Feb 15 |
Externally published | Yes |
Keywords
- (4β-Substituted)-l-prolylpyrrolidine
- 1,2,4-Thiadiazol-5-yl-piperazine
- DPP-IV inhibitor
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry