biostudies-literatureNguyen MMinistry of Health and WelfareChonnam National UniversityNational Research Foundation of Korea1131-1136https://www.ebi.ac.uk/biostudies/studies/S-EPMC9290037biostudies-literatureUnknown13(7)On the basis of the previously reported polypharmacological profile of truncated d-1'-homologated adenosine derivatives [J. Med. Chem.2020, 63, 16012], the l-nucleoside analogues were synthesized using computer-aided design and evaluated for biological activity. The target molecules were synthesized from d-ribose via the key intramolecular cyclization of the monotosylate and Mitsunobu condensation. The peroxisome proliferator-activated receptor (PPAR) binding activities of l-nucleoside analogue <b>2d</b> (<i>K</i> _i = 4.3 μM for PPARγ and 1.0 μM for PPARδ) were significantly improved in comparison with those of the d-nucleoside compound <b>1</b> (11.9 and 2.7 μM, respectively). In addition, the l-nucleosides showed more potent adiponectin-secretion-promoting activity than the d-ACS medicinal chemistry lettersDesign, Synthesis, and Biological Activity of l-1'-Homologated Adenosine Derivatives.PMC92900372021-2440NRF-2022R1I1A3056585NRF-2019R1F1A1063905HI20C0079NRF-2019R1A2C2085749Nguyen YKim GChoi HJeong LSPham LNoh MHyun YEKim JANguyen MAn SfalseDesign, Synthesis, and Biological Activity of l-1'-Homologated Adenosine Derivatives.On the basis of the previously reported polypharmacological profile of truncated d-1'-homologated adenosine derivatives [J. Med. Chem.2020, 63, 16012], the l-nucleoside analogues were synthesized using computer-aided design and evaluated for biological activity. The target molecules were synthesized from d-ribose via the key intramolecular cyclization of the monotosylate and Mitsunobu condensation. The peroxisome proliferator-activated receptor (PPAR) binding activities of l-nucleoside analogue <b>2d</b> (<i>K</i> _i = 4.3 μM for PPARγ and 1.0 μM for PPARδ) were significantly improved in comparison with those of the d-nucleoside compound <b>1</b> (11.9 and 2.7 μM, respectively). In addition, the l-nucleosides showed more potent adiponectin-secretion-promoting activity than the d-2022-01-01T00:00:00Z2022 Jul2026-05-28T01:23:16.771Z2025-04-07T10:19:38.201ZS-EPMC92900373585987510.1021/acsmedchemlett.2c00159