Method of identifying bioisosteres of 1,2,3-triazoles and amides

A method for creating and synthesizing new bioisosteres of a molecule, the method comprising:

• selecting a first molecule of interest having an amide group as a first bioisostere;
• replacing the amide group of the first molecule of interest with a 1,2,3-triazole group as a second bioisostere to obtain a second molecule with the second bioisostere;
• evaluating similarities between the first bioisostere and the second bioisostere according to a method comprising:
• completing a quantum mechanics (QM) simulation for the first and second molecules containing first and second bioisosteres;
• calculating average electron density (AED) values corresponding to the first and second bioisosteres in the first and second molecules;
• and
• confirming experimentally observed bioisosterism between the 1,2,3-triazole group and the amide group based on the calculated AED values being within 10% of one another;
• identifying the calculated AED values equivalent between the first and second bioisosteres based on the calculated AED values being within 10% of one another;
• identifying additional sets of atoms having calculated AED values corresponding to the calculated AED values equivalent between the first and second bioisosteres;
• replacing the amide group of the first molecule of interest with one of the identified additional sets of atoms to create a third molecule with a third bioisiostere;
• and
• synthesizing the third molecule with the third bioisostere.

A method for creating and synthesizing new bioisosteres of a molecule, the method comprising:

• selecting two molecules each having a group that may be bioisosteric to one another;
• calculating average electron density (AED) values corresponding to each said group that may be bioisosteric to one another;
• identifying any of the calculated AED values of each molecule being within 10% of one another;
• when the calculated AED values of the group that may be bioisosteric of one of the two molecules are within 10% of the calculated AED values of the group that may be bioisosteric of the other of the two molecules, replacing the group that may be bioisosteric of the one of the two molecules with the group that may be bioisosteric of the other of the two molecules to obtain a third molecule;
• and
• synthesizing the third molecule.