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

The synthesis and SAR of a novel class of spirobenzofuranpiperidinyl-derived alkanoic acids 6-34 as sphingosine S1P receptor agonists are described. The target compounds generally elicit high S1P receptor agonistic potencies and in general are selective against both S1P and S1P 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.