Polypharmacology of conformationally locked methanocarba nucleosides

Synthesis and Anti-Renal Fibrosis Activity of Conformationally Locked Truncated 2-Hexynyl-N6-Substituted-(N)-Methanocarba-nucleosides as A3 Adenosine Receptor Antagonists and Partial Agonists

Truncated N(6)-substituted-(N)-methanocarba-adenosine derivatives with 2-hexynyl substitution were synthesized to examine parallels with corresponding 4'-thioadenosines. Hydrophobic N(6) and/or C2 substituents were tolerated in A3AR binding, but only an unsubstituted 6-amino group with a C2-hexynyl group promoted high hA2AAR affinity. A small hydrophobic alkyl (4b and 4c) or N(6)-cycloalkyl gro...

Conformationally Constrained Nucleosides, Nucleotides and Oligonucleotides

Flexible access to conformationally-locked bicyclic morpholines.

A preparatively accessible route to a series of conformationally-locked bicyclic morpholines has been developed. This flexible approach allows for diversification in order for a small array of lead-like scaffolds to be synthesised from readily available key building blocks.

Towards conformationally-locked difluorosugar analogues: an unexpected sense of dihydroxylation.

Difluorinated cyclooctenones, synthesised using RCM, can be used as templates for stereoselective oxidative transformations to products that undergo transannular reactions to afford conformationally-locked analogues of 2-deoxy-2,2-difluorosugars with different stereochemical relationships between the C-2 and C-3 hydroxyl groups.

Conformationally locked bicyclo[4.3.0]nonane carbanucleosides: synthesis and bio-evaluation.

D-Ribose was converted into 3 novel carbobicyclic nucleosides bearing a bicyclo[4.3.0]nonane framework in 16-19 steps with 5-12% overall yields involving a Wittig olefination and an intramolecular Diels-Alder reaction as the key steps. The present synthesis also provides an efficient entry for chiral hydrindenones. The conformation studies of these carbanucleosides and their bio-evaluation as p...