Author/Authors :
Douglas F. Burdi، نويسنده , , Shannon Chi، نويسنده , , Karen Mattia، نويسنده , , Celeste Harrington، نويسنده , , Zhan Shi، نويسنده , , Shaowu Chen، نويسنده , , Swanee Jacutin-Porte، نويسنده , , Robert Bennett، نويسنده , , Kenneth Carson، نويسنده , , Wei Yin، نويسنده , , Vikram Kansra، نويسنده , , Jose-Angel Gonzalo، نويسنده , , Anthony Coyle، نويسنده , , Bruce Jaffee، نويسنده , , Timothy Ocain، نويسنده , , Marty Hodge، نويسنده , , Gregory LaRosa، نويسنده , , Geraldine Harriman، نويسنده ,
Abstract :
The identification, optimization, and structure–activity relationship (SAR) of small-molecule CCR4 antagonists is described. An initial screening hit with micromolar potency was identified that was optimized to sub-micromolar binding potency by enantiomer resolution, halogenation of the naphthalene ring, and extension of the alkyl chain linker between the central piperidine ring and the terminal aryl group. An antagonist was identified that showed good cross-reactivity against the mouse receptor and inhibited CCR4-based cell recruitment in dose-dependent fashion.
