136749-03-6Relevant articles and documents
Discovery and structure-activity relationship of N-(ureidoalkyl)-benzyl-piperidines as potent small molecule CC chemokine receptor-3 (CCR3) antagonists
De Lucca, George V.,Kim, Ui T.,Johnson, Curt,Vargo, Brian J.,Welch, Patricia K.,Covington, Maryanne,Davies, Paul,Solomon, Kimberly A.,Newton, Robert C.,Trainor, George L.,Decicco, Carl P.,Ko, Soo S.
, p. 3794 - 3804 (2007/10/03)
Structure-activity relationship (SAR) studies of initial screening hits from our corporate library of compounds and a structurally related series of CCR1 receptor antagonists were used to determine that an N-(alkyl)benzylpiperidine is an essential pharmacophore for selective CCR3 antagonists. Further SAR studies that introduced N-(ureidoalkyl) substituents improved the binding potency of these compounds from the micromolar to the low nanomolar range. This new series of compounds also displays highly potent, in vitro functional CCR3-mediated antagonism of eotaxin-induced Ca2+ mobilization and chemotaxis of human eosinophils.
Separation of α1 Adrenergic and N-Methyl-D-aspartate Antagonist Activity in a Series of Ifenprodil Compounds
Chenard, B. L.,Shalaby, I. A.,Koe, B. K.,Ronau, R. T.,Butler, T. W.,et al
, p. 3085 - 3090 (2007/10/02)
Ifenprodil (1) represents a new class of N-methyl-D-aspartate (NMDA) antagonist.This drug also possesses potent activity at several other brain receptors (most notably α1 adrenergic receptors).We have prepared the enantiomers and diastereomers of ifenprodil along with a series of partial structures in order to explore the basic structure activity relations within this class of compounds.From this study, it is clear that α1 adrenergic and NMDA receptor activities may be separated by selection of the threo relative stereochemistry.Examination of the optical isomers of threo-ifenprodil (2) reveals that no further improvement in receptor selectivity is gained from either antipode.Individual removal of most of the structural fragments from the ifenprodil molecule generally results in less active compounds although fluorinated derivative 9 with threo relative stereochemistry is somewhat more potent and substantially more selective for the NMDA receptor.Finally a minimum structure for activity in this series (14) has been identified.This stripped-down version of ifenprodil possesses nearly equivalent affinity for the NMDA receptor with no selectivity over α1 adrenergic receptors.
