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CCR2 receptor antagonists: optimization of biaryl sulfonamides to increase activity in whole blood |
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| Authors: | Wang Gren Z Haile Pamela A Daniel Tom Belot Benjamin Viet Andrew Q Goodman Krista B Sha Deyou Dowdell Sarah E Varga Norbert Hong Xuan Chakravorty Subhas Webb Christine Cornejo Carla Olzinski Alan Bernard Roberta Evans Christopher Emmons Amanda Briand Jacques Chung Chun-Wa Quek Ruben Lee Dennis Gough Peter J Sehon Clark A |
| Institution: | Pattern Recognition Receptors DPU, ImmunoInflammation Therapeutic Area Unit, GlaxoSmithKline, 1250 South Collegeville Road, PA 19426, USA. |
| Abstract: | A series of biarylsulfonamides was identified as hCCR2 receptor antagonist but suffered from high plasma protein binding resulting in a >100 fold shift in activity in a functional GTPγS assay run in tandem in the presence and absence of human serum albumin. Introduction of an aryl amide with ethylenediamine linker led to compounds with reduced shifts and improved activity in whole blood. |
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