1126367-80-3Relevant articles and documents
Discovery of novel hedgehog antagonists from cell-based screening: Isosteric modification of p38 bisamides as potent inhibitors of SMO
Yang, Bin,Hird, Alexander W.,Russell, Daniel John,Fauber, Benjamin P.,Dakin, Les A.,Zheng, Xiaolan,Su, Qibin,Godin, Robert,Brassil, Patrick,Devereaux, Erik,Janetka, James W.
supporting information; experimental part, p. 4907 - 4911 (2012/08/07)
Cell-based subset screening of compounds using a Gli transcription factor reporter cell assay and shh stimulated cell differentiation assay identified a series of bisamide compounds as hedgehog pathway inhibitors with good potency. Using a ligand-based optimization strategy, heteroaryl groups were utilized as conformationally restricted amide isosteres replacing one of the amides which significantly increased their potency against SMO and the hedgehog pathway while decreasing activity against p38α kinase. We report herein the identification of advanced lead compounds such as imidazole 11c and 11f encompassing good p38α selectivity, low nanomolar potency in both cell assays, excellent physiochemical properties and in vivo pharmacokinetics.
HETEROCYCLIC AMIDES USEFUL FOR THE TREATMENT OF CANCER AND PSORIASIS
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Page/Page column 65-66, (2009/04/25)
The present disclosure relates to heterocyclic amide compounds, which are useful for inhibiting the Hedgehog pathway, and their use in treating a disease or medical condition mediated alone or in part by Hedgehog pathway inhibition. Also disclosed are methods for manufacture of these compounds, pharmaceutical compositions including these compounds, and use of these compounds in the manufacture of medicaments for treating such diseases and medical conditions in a subject. Formula (IA) with the provisio that either R2or R3 is (Z).
