They change one tiny piece at a time.
3-Methoxy-5-methyl-2-pyrazinamine is the kind of small molecular building block that makes this possible.
At its center is a pyrazine ring: a six-membered aromatic ring containing two nitrogen atoms. Add an amino group, a methoxy group, and a methyl group, and chemists have a compact fragment ready to attach to something larger.
In the 1990s, researchers at Zeneca were studying molecules that could block the endothelin-A receptor, part of a signaling system involved in blood-vessel contraction.
They tried changing the nitrogen-containing ring in their molecules.
Global Chemical Database