From rigid cyclic templates to conformationally stabilized acyclic scaffolds. Part I: the discovery of CCR3 antagonist development candidate BMS-639623 with …

…, P Reddy, AJ Tebben, GV DeLucca, DA Wacker…

Index: Santella III, Joseph B.; Gardner, Daniel S.; Yao, Wenqing; Shi, Chongsheng; Reddy, Prabhakar; Tebben, Andrew J.; DeLucca, George V.; Wacker, Dean A.; Watson, Paul S.; Welch, Patricia K.; Wadman, Eric A.; Davies, Paul; Solomon, Kimberly A.; Graden, Dani M.; Yeleswaram, Swamy; Mandlekar, Sandhya; Kariv, Ilona; Decicco, Carl P.; Ko, Soo S.; Carter, Percy H.; Duncia, John V. Bioorganic and Medicinal Chemistry Letters, 2008 , vol. 18, # 2 p. 576 - 585

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Citation Number: 26

Abstract

Conformational analysis of trans-1, 2-disubstituted cyclohexane CCR3 antagonist 2 revealed that the cyclohexane linker could be replaced by an acyclic syn-α-methyl-β- hydroxypropyl linker. Synthesis and biological evaluation of mono-and disubstituted propyl linkers support this conformational correlation. It was also found that the α-methyl group to the urea lowered protein binding and that the β-hydroxyl group lowered affinity for ...

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