Peer Reviewed

1

Document Type

Article

Publication Date

23-5-2011

Keywords

Combinatorial Chemistry Techniques, Databases, Chemical, Drug Design, Drug Discovery, Internet, Ligands, Molecular Structure, Proteins, Small Molecule Libraries, User-Computer Interface

Funder/Sponsor

Health Research Board, Irish Research Council, Science Foundation Ireland

Comments

The original article is available at http://pubs.acs.org/doi/abs/10.1021/ci100443x

Abstract

The synthetic feasibility of any compound library used for virtual screening is critical to the drug discovery process. TIN, a recursive acronym for 'TIN Is Not commercial', is a virtual combinatorial database enumeration of diversity-orientated multicomponent syntheses (MCR). Using a 'one-pot' synthetic technique, 12 unique small molecule scaffolds were developed, predominantly styrylisoxazoles and bis-acetylenic ketones, with extensive derivatization potential. Importantly, the scaffolds were accessible in a single operation from commercially available sources containing R-groups which were then linked combinatorially. This resulted in a combinatorial database of over 28 million product structures, each of which is synthetically feasible. These structures can be accessed through a free Web-based 2D structure search engine or downloaded in SMILES, MOL2, and SDF formats. Subsets include a 10% diversity subset, a drug-like subset, and a lead-like subset that are also freely available for download and virtual screening ( http://mmg.rcsi.ie:8080/tin ).

Disciplines

Life Sciences

Citation

Dorschner KV, Toomey D, Brennan MP, Heinemann T, Duffy FJ, Nolan KB, Cox D, Adamo MFA, Chubb AJ. IN-a combinatorial compound collection of synthetically feasible multicomponent synthesis products. Journal of Chemical Information and Modeling. 2011;51(5):986-95.

PubMed ID

21495663

DOI Link

10.1021/ci100443x

Included in

Life Sciences Commons

Share

COinS