382637-43-6Relevant 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 (2005)
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.
SUBSTITUTED HETEROCYCLIC AMIDE COMPOUND AND PREPARATION METHOD THEREFOR AND PHARMACEUTICAL USE THEREOF
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Paragraph 0140-0141; 0215-0216, (2022/02/02)
Provided are a substituted heterocyclic amide compound having a selective inhibitory effect on RIPK1, and a pharmaceutically acceptable salt, a stereoisomer, a solvate or a prodrug thereof, and a pharmaceutical composition containing the compound, and the
O-GLYCOPROTEIN-2-ACETAMIDO-2-DEOXY-3-D-GLYCOPYRANOSIDASE INHIBITORS
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Paragraph 0085; 0087, (2019/10/04)
Described herein are compounds represented by formula (I") or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising the same and methods of preparing and using the same. The variables Ar, Ra, Rb, m, n, Y
Discovery of CC chemokine receptor-3 (CCR3) antagonists with picomolar potency
De Lucca, George V.,Ui, Tae Kim,Vargo, Brian J.,Duncia, John V.,Santella III, Joseph B.,Gardner, Daniel S.,Zheng, Changsheng,Liauw, Ann,Wang, Zhang,Emmett, George,Wacker, Dean A.,Welch, Patricia K.,Covington, Maryanne,Stowell, Nicole C.,Wadman, Eric A.,Das, Anuk M.,Davies, Paul,Yeleswaram, Swamy,Graden, Danielle M.,Solomon, Kimberly A.,Newton, Robert C.,Trainor, George L.,Decicco, Carl P.,Ko, Soo S.
, p. 2194 - 2211 (2007/10/03)
Starting with our previously described20 class of CC chemokine receptor-3 (CCR3) antagonist, we improved the potency by replacing the phenyl linker of 1 with a cyclohexyl linker and by replacing the 4-benzylpiperidine with a 3-benzylpiperidine. The resulting compound, 32, is a potent and selective antagonist of CCR3. SAR studies showed that the 3-acetylphenyl urea of 32 could be replaced with heterocyclic ureas or heterocyclic-substituted phenyl ureas and still maintain the potency (inhibition of eotaxin-induced chemotaxis) of this class of compounds in the low-picomolar range (IC50 = 10-60 pM), representing some of the most potent CCR3 antagonists reported to date. The potency of 32 for mouse CCR3 (chemotaxis IC50 = 41 nM) and its oral bioavailability in mice (20% F) were adequate to assess the efficacy in animal models of allergic airway inflammation. Oral administration of 32 reduced eosinophil recruitment into the lungs in a dose-dependent manner in these animal models. On the basis of its overall potency, selectivity, efficacy, and safety profile, the benzenesulfonate salt of 32, designated DPC168, entered phase I clinical trials.
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.
