745815-09-2Relevant articles and documents
Efficient preparation of (3S)-3-(4-fluorobenzyl)piperidinium mandelate
Emmett, George C.,Cain, Gary A.,Estrella, Melissa J.,Holler, Edd R.,Piecara, James S.,Blum, Andrew M.,Mical, Alfred J.,Teleha, Christopher A.,Wacker, Dean A.
, p. 92 - 96 (2007/10/03)
Methods for the preparation of (3S)-3-(4-fluorobenzyl)piperidine (2) and its mandelate salt (9) are described. The first generation synthesis started from 3-benzylpiperidone, and required Boc protection of the nitrogen for efficient separation of the enantiomers using chromatography on a chiral stationary phase. Subsequently, a resolution method using (R)-mandelic acid, produced high %ee salt 9 after recrystallization and eliminated the need for Boc protection. The third generation route, starting from pyridine-3- carboxaldehyde, led to a streamlined synthesis of racemate 2 and was optimized for producing multi-hundred gram quantities of the chiral salt.
Discovery of N-propylurea 3-benzylpiperidines as selective CC chemokine receptor-3 (CCR3) antagonists
Varnes, Jeffrey G.,Gardner, Daniel S.,Santella III, Joseph B.,Duncia, John V.,Estrella, Melissa,Watson, Paul S.,Clark, Cheryl M.,Ko, Soo S.,Welch, Patricia,Covington, Maryanne,Stowell, Nicole,Wadman, Eric,Davies, Paul,Solomon, Kimberley,Newton, Robert C.,Trainor, George L.,Decicco, Carl P.,Wacker, Dean A.
, p. 1645 - 1649 (2007/10/03)
The discovery of novel and selective small molecule antagonists of the CC Chemokine Receptor-3 (CCR3) is presented. Simple conversion from a 4- to 3-benzylpiperidine gave improved selectivity for CCR3 over the serotonin 5HT2A receptor. Chiral resolution and exploration of mono- and disubstitution of the N-propylurea resulted in several 3-benzylpiperidine N-propylureas with CCR3 binding IC50s under 5 nM. Data from in vitro calcium mobilization and chemotaxis assays for these compounds ranged from high picomolar to low nanomolar EC50s and correlated well with antagonist binding IC50s.
