TIN-a combinatorial compound collection of synthetically feasible multicomponent synthesis products

J Chem Inf Model. 2011 May 23;51(5):986-95. doi: 10.1021/ci100443x. Epub 2011 Apr 15.

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 ).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Ligands
  • Proteins
  • Small Molecule Libraries