Structure-activity relationship of short-chain sphingoid bases as inhibitors of sphingosine kinase (original) (raw)

Short-chain sphinganine analogues 8, 9, 18, and 19, as well as 3-fluoro-sphingosine analogues 25 and 26 were synthesized. Their potential as sphingosine kinase inhibitors was investigated, in combination with previously synthesized sphingosine and fluorinated sphinganine analogues. De Jonghe et al. /Bioorg. Med. Chem. Lett. 9 (1999) 3175-3180 D,L-threo-dihydrosphingosine (or D,L-threo-sphinganine) 8 and N,N-dimethylsphingosine 9 are known competitive inhibitors of sphingosine kinase ). To further explore the structural requirements, necessary for inhibition of sphingosine kinase, we previously synthesized sphingosine analogues 9 and fluorinated sphinganine analogues, t° We have now prepared a new series of sphinganine derivatives and 3fluoro-sphingosine analogues in order to comparatively assess these compounds as potential inhibitors of