66865-86-9Relevant articles and documents
Structure-Activity relationships and molecular modeling of sphingosine kinase inhibitors
Baek, Dong Jae,MacRitchie, Neil,Anthony, Nahoum G.,MacKay, Simon P.,Pyne, Susan,Pyne, Nigel J.,Bittman, Robert
, p. 9310 - 9327 (2013)
The design, synthesis, and evaluation of the potency of new isoform-selective inhibitors of sphingosine kinases 1 and 2 (SK1 and SK2), the enzyme that catalyzes the phosphorylation of d-erythro-sphingosine to produce the key signaling lipid, sphingosine 1-phosphate, are described. Recently, we reported that 1-(4-octylphenethyl)piperidin-4-ol (RB-005) is a selective inhibitor of SK1. Here we report the synthesis of 43 new analogues of RB-005, in which the lipophilic tail, polar headgroup, and linker region were modified to extend the structure-activity relationship profile for this lead compound, which we explain using modeling studies with the recently published crystal structure of SK1. We provide a basis for the key residues targeted by our profiled series and provide further evidence for the ability to discriminate between the two isoforms using pharmacological intervention.
Synthesis and Pharmacological Studies of 4,4-Disubstituted Piperidines: A New Class of Compounds with Potent Analgesic Properties
Huegi, Bruno S.,Ebnoether, Anton M.,Rissi, Erwin,Gadient, Fulvio,Hauser, Daniel,et al.
, p. 42 - 50 (2007/10/02)
A series of 4,4-disubstituted piperidines has been synthesized and evaluated for analgesic activity.Several of these analogues show analgesic potency comparable to morphine in the mouse writhing and tail-flick tests.A number of compounds exhibit high affi
