What happens when you cross Matched Molecular Pair Analysis (MMPA) with reactions? Why, of course, you get a new paradigm in drug discovery, Matched Molecular Reactants!
Well, let’s think about it for a second. If you take the reactants and the products and look for matched molecular pairs combining both, what you will find are reactions that involve single R group transformations. We can call these Matched Molecular Reactants, but they are probably more commonly known as functional group transformations, e.g. -OH to -Cl.
So, what are the most common functional group transformations in a typical ELN? Well, I can’t show you that but I can show you the results when this analysis is applied to reactions in the US patent literature (this data courtesy of Daniel). The following table show SMILES for the R group together with the observed frequency for the 15 most common transformations:
*[N+](=O)[O-] --> *N 21456 *C --> *[H] 21165 *[H] --> *C 15583 *CC --> *[H] 12914 *C(=O)OC --> *C(=O)O 11729 *C(=O)OC(C)(C)C --> *[H] 9149 *NC(=O)OC(C)(C)C --> *N 8054 *C(=O)OCC --> *C(=O)O 7673 *Cc1ccccc1 --> *[H] 6695 *OC --> *O 6339 *[H] --> *Br 6141 *O --> *Cl 4852 *OCc1ccccc1 --> *O 4662 *[H] --> *CC 3980 *C(=O)O --> *C(=O)OC 3888
It seems that the majority of reactions tend to make molecules smaller. If this keeps up, we’ll soon be left with nothing!