Functional Switch between Pharmacophore and Directing Group and Their Application in Drug Discovery and Development via C-H Activation and Functionalization

The functional switch of a C-H activation directing group to a pharmacophore is introduced and analyzed, and the value of the pharmacophore and the application of C-H activation are exemplified. It is concluded that many pharmacophores, such as N-containing heteroaromatic, nitrile, carboxylic acid, amide and sulfonamide groups, are ideal directing groups for C-H activation enabling the subsequent stages of drug synthesis, and showing that there is a correlation between a directing group and a pharmacophore. The late-stage functionalization will greatly simplify and effectively improve the possibility of discovering new drugs and potentially shortening the overall synthesis. The latest breakthroughs of C-H activation and application in the drug discovery process are reviewed as case studies, providing several industrial examples of using a pharmacophore as directing group for drug synthesis. It is believed that this development will promote a more rapid and green drug synthesis.