Focused Sets: Compounds for Antibacterial Research

In antibacterial Drug Discovery the screening of randomly assembled, diverse compound libraries has produced extremely low hit rates [1]. Moreover, in-vitro screening often delivers non-drug like and non-target specific structures which tend to face serious efficacy issues in subsequent in vivo experiments. To address this major challenge, it is critical to access compound libraries which are capable of delivering excellent chemical starting points for completely new classes of antibacterials. A large proportion of known antibacterials have come from natural products and these compounds clearly have structures and properties which have made them a particularly rich source of diversification [2].

ASINEX has developed a unique compound library for antibacterial research based on the proprietary natural product-like scaffolds that provide great skeletal diversity combined with the presence of polar functional groups and multiple stereogenic centers. The scaffolds and final compounds have been produced by utilizing stereo-controlled transformations and efficient coupling reactions, generating specific structural elements inherent to antibacterial agents: cyclic polyethers, carbohydrate-like compounds, peptide-like macrocycles and macrolactams. It is also significant that the library occupies the unique physicochemical space of known antibiotics, which enhances the chances of finding high quality hits in both target-directed and whole-cell assays [3].  Specific emphasis was put into challenges of the cell penetration for Gram-negative pathogens where the compounds with only a very narrow distribution of molecular weights, lipophilicity and polar surface area can effectively work [3].

1. David J. Payne et al. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nature Reviews Drug Discovery  2007, N6, pp 29-40. DOI:10.1038/nrd2201.

2. Herbert A Kirst, Developing new antibacterials through natural product research. Expert Opinion on Drug Discovery. 2013, 8, N5, pp 479-493. DOI:10.1517/17460441.2013.779666

3.O'Shea R, Moser HE, Physicochemical properties of antibacterial compounds: implications for drug discovery, J Med Chem. 2008, 51(10), pp 871-8. DOI:10.1021/jm700967e.

Download Antibacterial SDF file (3041 compounds, version Aug.2015).

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