Matched Molecular Reactants

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!