1-(3-Cyanobenzylpiperidin-4-yl)-5-methyl-4-phenyl-1, 3-dihydroimidazol-2-one: A selective high-affinity antagonist for the human dopamine D4 receptor with excellent …

…, K Bonner, F Emms, R Marwood, S Patel…

Index: Carling, Robert W.; Moore, Kevin W.; Moyes, Christopher R.; Jones, Elizabeth A.; Bonner, Katrine; Emms, Frances; Marwood, Rosemary; Patel, Shil; Patel, Smita; Fletcher, Alan E.; Beer, Margaret; Sohal, Bindi; Pike, Andrew; Leeson, Paul D. Journal of Medicinal Chemistry, 1999 , vol. 42, # 14 p. 2706 - 2715

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Citation Number: 59

Abstract

After the requirement of pseudocycle formation in the ureas 3 and 7 for hD4 binding and selectivity was confirmed, structural hybridization with the known hD4 ligand 2 led to the design and identification of the lead 4-(2-oxo-1, 3-dihydroimidazol-2-yl) piperidine 8. Optimization studies were carried out on 8 with the aim of achieving 1000-fold selectivity for hD4 over all other receptors while retaining the good pharmacokinetic properties of the ...