Pyridazine

Pyridazine has attracted growing interest in drug discovery as a privileged scaffold and strategic bioisostere for phenyl and other heteroaromatic rings. The ring exhibits unique physicochemical properties characterised by mild alkalinity, a high dipole moment, a π-deficient aromatic skeleton that facilitates π-π stacking interactions, and two sp2 nitrogen atoms that mediate drug-target interactions as hydrogen-bond acceptors. These properties contribute to unique applications in molecular recognition, while the inherent polarity, low cytochrome P450 inhibitory effects, and potential to reduce interaction with the cardiac hERG potassium channel add additional value in drug discovery and development. Pyridazine can improve the physicochemical properties of drug molecules by increasing aqueous solubility and bioavailability, including to the CNS, while also facilitating crystallisation of drug substances, which is of practical value in industrial development. These properties make pyridazine a useful tool for scaffold hopping and lead optimisation, particularly in cases where replacing a phenyl or pyridine ring is required to improve solubility, reduce metabolic liability, or sharpen target selectivity.

Pyridazines have seen use across oncology, cardiovascular, inflammatory, and CNS programmes. Relugolix (Orgovyx, Myovant Sciences) is an FDA-approved first-in-class oral non-peptide GnRH receptor antagonist containing a pyridazine ring, approved in December 2020 for the treatment of advanced prostate cancer, and the first orally administered GnRH antagonist approved for any indication. Deucravacitinib (Sotyktu, Bristol Myers Squibb) is an FDA-approved first-in-class oral allosteric TYK2 inhibitor incorporating a pyridazine moiety, approved in September 2022 for adults with moderate-to-severe plaque psoriasis, acting through a selective pseudokinase regulatory domain mechanism that distinguishes it from ATP-competitive JAK inhibitors.

Our range of Pyridazines features novel substitutions and the incorporation of synthetically tractable functional groups such as boronic acids and esters, amines, carboxylic acids, ketones, hydroxyls and halogens to enable expedient synthetic strategies.

Please examine a selection of Pyridazines in our catalogue. The full range can be found using the substructure feature of our Search tools.