Biological and Structural Characterization of Rotamers of C-C Chemokine Receptor Type 5 (CCR5) Inhibitor GSK214096.

We recently reported the discovery of preclinical CCR5 inhibitor GSK214096, 1 (J. Med. Chem.

An enyne cycloisomerization approach to the triple reuptake inhibitor GSK1360707F.

The triple reuptake inhibitor GSK1360707F was synthesized via an efficient and scalable route that features an enyne cycloisomerization reaction catalyzed by either Pt(II) or Au(I). Key aspects of this work such as the choice of the nitrogen protecting group and initial enantioselectivity studies are discussed.

Function-oriented synthesis: studies aimed at the synthesis and mode of action of 1alpha-alkyldaphnane analogues.

[reaction: see text] An efficient synthetic route to the ABC tricyclic core of 1alpha-alkyldaphnanes has been developed. The conformational bias imparted by the C6-C9 oxo-bridge of BC-ring system 12 was used to elaborate the ABC-ring system precursor including the introduction of the beta-C5 hydroxyl group. A completely diastereoselective palladium-catalyzed enyne cyclization was then employed to establish the A-ring with a C1 appendage.