The P1 binding pocket is an intriguing region of the Mpro enzyme to target. In the fragment screen, many fragments bound in this location, with a hydrogen bond between the ligand and the epsilon nitrogen of HIS163. There are three examples of fragments with a 3-pyridine moiety (x0107, x0434, and x0678) and an additional closely related fragment with a pyrimidine (x0995). The pattern is obsured a little bit with other functional groups (i.e. x0426 and x0540 with 4-pyridine, and x0967 with a phenol) distracting from the 3-pyridine motif. For example, the 4-pyridine fragments could be useful except that the side groups extend into the solvent, making the 3-pyridine the preferred binding motif. x0995 presents an example fragment with an aniline-NH2 group in a beneficial location, a highly polar region where the N-terminal SER1 from chain B interacts with ASP142 and the backbone of PHE140. Also, x1093 offers an example of a larger ring system for increasing the surface contact area and the potential for additional polar and/or hydrogen bonding interactions to further increase the affinity of a piece of the drug molecule at this region of the binding pocket. Another interesting feature of this fragment screen is the similarity of binding pose between x0678 and x0434. The 3-pyridine side of the molecules are exactly the same and bind almost identically to the protein. The opposite side of the molecules differ, with each offering advantages or disadvantages for further exploration. Therefore, I am proposing a set of compounds based on the x0434 and x0678 fragments with varying extensions to the 3-pyridine motif. These compounds all maintain the hydrogen bond acceptor with the epsilon nitrogen of HIS163 and incorporate a nitrogen, either exocyclic as demonstrated with x0995 or incorporated into larger 6+5 or 6+6 bicyclic heteroaromatic rings, to interact with the N-terminus of chain B. These compounds offer varying protonation states and angles for interacting with this key region of the enzyme.