Lead optimization of a sulfonylurea-based piperazine pyridazinone series of glucan synthase inhibitors.

Medicinal Chemistry Department, Albany Molecular Research, Inc. (AMRI), 26 Corporate Circle, Albany, NY 12203, USA.

Bioorganic & medicinal chemistry letters 2012 Jul 15

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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. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

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. Lead optimization of a sulfonylurea-based piperazine pyridazinone series of glucan synthase inhibitors. Bioorganic & medicinal chemistry letters. 2012 Jul 15;22(14):4896-9