In our internal database of drugs and active compounds of more than 2,500 molecules, 63 entries have a quinoline in their substructure. This may seem poor, but if you compare with the 79 compounds having a naphtyl substructure and the 56 compounds with a biphenyl, you realize that quinolines remain an important feature for active molecules. Moreover the substructure was listed in the most common atomic frameworks in drugs (G. W. Bemis and M. A. Murcko, “The Properties of Known Drugs. 1. Molecular Frameworks”, J. Med. Chem., 1996, 39, 2887-2893).

Quinolines are conveniently synthesized in one step from isatin and an acetophenone. This method is suitable for parallel synthesis since the final compounds all have an active carboxylic acid in the 4-position. The diversity of acetophenones is limited but we were able to select 16 starting materials and 80 diverse partners to explore an optimal space around the quinoline-4-carboxamide scaffold.

Many applications can be considered for this collection of compounds within the Lipinski’s rules, as diverse as amine and peptide GPCR inhibition, ion channels modulators and enzyme inhibitors. Former active molecules sharing the quinoline carboxamide substructure are detailed and discussed in the brochure of the library.

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