John J. M. Wiener

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In an attempt to search for a new class of antibacterial agents, we have discovered a series of pyrazole analogs that possess good antibacterial activity for Gram-positive and Gram-negative organisms via inhibition of type II bacterial topoisomerases. We have investigated the structure-activity relationships of this series, with an emphasis on the length(More)
We have previously reported a novel class of tetrahydroindazoles that display potency against a variety of Gram-positive and Gram-negative bacteria, potentially via interaction with type II bacterial topoisomerases. Herein are reported SAR investigations of this new series. Several compounds possessing broad-spectrum potency were prepared. Further, these(More)
We introduce Scaffold Explorer, an interactive tool that allows medicinal chemists to define hierarchies of chemical scaffolds and use them to explore their project data. Scaffold Explorer allows the user to construct a tree, where each node corresponds to a specific scaffold. Each node can have multiple children, each of which represents a more refined(More)
We introduce Single R-Group Polymorphisms (SRPs, pronounced 'sharps'), an intuitive framework for analyzing substituent effects and activity cliffs in a single congeneric series. A SRP is a pair of compounds that differ only in a single R-group position. Because the same substituent pair may occur in multiple SRPs in the series (i.e., with different(More)
Our laboratory has been engaged in the design of broadly useful new strategies for enantioselective catalysis that utilize organic chemicals as reaction catalysts. In our recent study, we reported that the LUMO-lowering activation of R,-unsaturated aldehydes using the reversible formation of iminium ions with chiral imidazolidinones 1 (eq 1) is a valuable(More)
The continual search for new antitumor and antiviral agents from marine sponge extracts has resulted in the identification of a number of structurally complex and diverse natural products with intriguing biological activity. In 1996 and 1997 Minale and co-workers reported the isolation and structural assignment of callipeltosides A–C (Figure 1), the first(More)
Cathepsin S has been of increasing interest as a target of medicinal chemistry efforts given its role in modulating antigen-presentation by major histocompatibility class II (MHC II) molecules as well as its involvement in extracellular proteolytic activities. Inhibition of the cathepsin S enzyme reduces degradation of the invariant chain, a crucial(More)
This paper describes a method for reducing the economic risks associated with predictable natural hazards by enhancing the resilience of national infrastructure systems. The three-step generalised framework is described along with examples. Step one establishes economic baseline growth without the disaster impact. Step two characterises economic growth(More)
Previously, benzthiazole containing LTA(4)H inhibitors were discovered that were potent (1-3), but were associated with the potential for a hERG liability. Utilizing medicinal chemistry first principles (e.g., introducing rigidity, lowering cLogD) a new benzthiazole series was designed, congeners of 1-3, which led to compounds 7a, 7c, 12a-d which exhibited(More)
Novel classes of tetrahydropyrido-pyrazole thioether amines and arylalkynes that display potency against human Cathepsin S have been previously reported. Here, key pharmacophoric elements of these two classes are merged, and SAR investigations of the P4 region are described, in conjunction with re-optimization of the P5 and P1/P1'/P3 regions. Identification(More)