- Lead optimization of a sulfonylurea-based piperazine pyridazinone series of glucan synthase inhibitors.
Lead optimization of a sulfonylurea-based piperazine pyridazinone series of glucan synthase inhibitors.
Bioorganic & medicinal chemistry letters (2012-06-13)
Andrew J Zych, Sang Q Lam, David M Jenkins, R Jason Herr, Pauline C Ting, Joe F Lee, Rongze Kuang, Heping Wu, David W Kim, Robert G Aslanian, Samuel Wainhaus, Todd A Black, Anthony Cacciapuoti, Paul M McNicholas, Yiming Xu, Scott S Walker
PMID22687744
摘要
The structure-activity relationship studies of a novel sulfonylurea series of piperazine pyridazine-based small molecule glucan synthase inhibitors is described. The optimization of PK profiles within the series led to the discovery of several compounds with improved pharmacokinetic profiles which demonstrated in vitro potency against clinically relevant strains. However, the advancement of compounds from this series into a non-lethal systemic fungal infection model failed to show in vivo efficacy.
材料