18552-90-4Relevant articles and documents
Discovery and Structure-Activity Relationships of Novel Template, Truncated 1′-Homologated Adenosine Derivatives as Pure Dual PPARγ/δModulators
An, Seungchan,Kim, Gyudong,Kim, Hyun Jin,Ahn, Sungjin,Kim, Hyun Young,Ko, Hyejin,Hyun, Young Eum,Nguyen, Mai,Jeong, Juri,Liu, Zijing,Han, Jinhe,Choi, Hongseok,Yu, Jinha,Kim, Ji Won,Lee, Hyuk Woo,Jacobson, Kenneth A.,Cho, Won Jea,Kim, Young-Mi,Kang, Keon Wook,Noh, Minsoo,Jeong, Lak Shin
, p. 16012 - 16027 (2021/01/09)
Following our report that A3 adenosine receptor (AR) antagonist 1 exhibited a polypharmacological profile as a dual modulator of peroxisome proliferator-activated receptor (PPAR)γ/δ, we discovered a new template, 1′-homologated adenosine analogues 4a-4t, as dual PPARγ/δmodulators without AR binding. Removal of binding affinity to A3AR was achieved by 1′-homologation, and PPARγ/δdual modulation was derived from the structural similarity between the target nucleosides and PPAR modulator drug, rosiglitazone. All the final nucleosides were devoid of AR-binding affinity and exhibited high binding affinities to PPARγ/δbut lacked PPARα binding. 2-Cl derivatives exhibited dual receptor-binding affinity to PPARγ/δ, which was absent for the corresponding 2-H derivatives. 2-Propynyl substitution prevented PPARδ-binding affinity but preserved PPARγaffinity, indicating that the C2 position defines a pharmacophore for selective PPARγligand designs. PPARγ/δdual modulators functioning as both PPARγpartial agonists and PPARδantagonists promoted adiponectin production, suggesting their therapeutic potential against hypoadiponectinemia-associated cancer and metabolic diseases.
Synthesis of purin-2-yl and purin-6-yl-aminoglucitols as C-nucleosidic ATP mimics and biological evaluation as FGFR3 inhibitors
Tak-Tak, Lotfi,Barbault, Florent,Maurel, Franois,Busca, Patricia,Le Merrer, Yves
, p. 1254 - 1262 (2011/04/23)
Two new series of C-nucleosidic ATP mimics have been synthesized using an efficient and versatile synthetic pathway. These compounds were designed as FGFR3 inhibitors using purine as a central scaffold. The two substituents, a polyhydroxylated ribose mimi
Linear and convergent approaches to 2-substituted adenosine-5′-N-alkylcarboxamides
Foitzik, Richard C.,Devine, Shane M.,Hausler, Nicholas E.,Scammells, Peter J.
experimental part, p. 8851 - 8857 (2009/12/26)
Herein we report both linear and convergent pathways for the preparation of 2-alkynyl substituted adenosine-5′-N-ethylcarboxamides via the versatile synthetic intermediate, 2-iodoadenosine-5′-N-ethylcarboxamide (13). The linear approach afforded 13 in an overall yield of 30% from guanosine over eight synthetic steps. The convergent approach was shorter, but proceeded in lower yield (five steps, 20% yield). Both approaches compare favourably with previously reported syntheses of 13, which has been prepared in 15% yield from guanosine over nine steps. 2-Iodoadenosine-5′-N-ethylcarboxamide (13) was subsequently converted to HENECA (2) and PHPNECA (3) to exemplify the utility of this approach for the preparation of?potent A2A adenosine receptor agonists. The linear approach was also amenable to the synthesis of 2-fluoropurine ribosides, which were subsequently elaborated into 2-alkylaminoadenosine-5′-N-ethylcarboxamides. Furthermore, both of these synthetic approaches are readily amenable to the synthesis of adenosine analogues with varied 2-, 6- and 5′-substitution patterns.
