Adri van den Hoogenband

Two novel syntheses of the histamine H3 antagonist thioperamide

Abstract The previously described route for the synthesis of the histamine H 3 antagonist thioperamide 3 has been improved considerably. Furthermore, two straightforward novel synthetic routes towards 3 are described herein. The last synthetic route (Scheme 3) is preferable as it is very suitable for the production of multigram quantities of thioperamide 3.

Spiro-1-benzofuranpiperidinylalkanoic acids as a novel and selective sphingosine S1P 5 receptor agonist chemotype

The synthesis and SAR of a novel class of spirobenzofuranpiperidinyl-derived alkanoic acids 6-34 as sphingosine S1P5 receptor agonists are described. The target compounds generally elicit high S1P5 receptor agonistic potencies and in general are selective against both S1P1 and S1P3 receptor subtypes. The key compound 32 shows a high bioavailability of 73% and a CNS/plasma ratio of 0.8 after oral administration in rats.