888973-03-3Relevant academic research and scientific papers
Zwitterionic CRTh2 antagonists
Luker, Tim,Bonnert, Roger,Paine, Stuart W.,Schmidt, Jerzy,Sargent, Carol,Cook, Anthony R.,Cook, Andrew,Gardiner, Philip,Hill, Steve,Weyman-Jones, Carol,Patel, Anil,Thom, Stephen,Thorne, Philip
, p. 1779 - 1788 (2011/05/05)
A novel series of zwitterions is reported that contains potent, selective antagonists of the chemoattractant receptor-homologous expressed on Th2 lymphocytes receptor (CRTh2 or DP2). A high quality lead compound 2 was discovered from virtual screening based on the pharmacophore features present in a literature compound 1. Lead optimization through side chain modification and preliminary changes around the acid are disclosed. Optimization of physicochemical properties (log D, MWt, and HBA) allowed maintenance of high CRTh2 potency while achieving low rates of metabolism and minimization of other potential concerns such as hERG channel activity and permeability. A step-change increase in potency was achieved through addition of a single methyl group onto the piperazine ring, which gave high quality compounds suitable for progression into in vivo studies.
PHENOXYACETIC ACID DERIVATIVES USEFUL FOR TREATING RESPIRATORY DISEASES
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Page/Page column 90, (2008/06/13)
The invention relates to substituted phenoxyacetic acids as useful pharmaceutical compounds for treating respiratory disorders, pharmaceutical compositions containing them, and processes for their preparation.Formula (I)
