Pyrimidine, also known as 1,3-diazobenzene, is a heterocyclic compound with the chemical formula C4H4N2. Pyrimidine is formed by substituting 2 nitrogen atoms for 2 carbons in the meta-position of benzene. It is a diazine and retains its aromaticity. Derivatives of pyrimidine widely exist in organic macromolecular nucleic acids, and many drugs also contain pyrimidine rings. In nucleic acids, three nucleobases are pyrimidine derivatives: cytosine, thymine and uracil. There are a variety of pyrimidine-containing drugs on the market, most of which are kinase inhibitors.
Novartis'HRO761 is an oral allosteric inhibitor targeting WRN helicase, aimed at treating microsatellite instability (MSI) or deficient mismatch repair (dMMR) tumors. WRN has emerged as a critical synthetic lethal target in MSI cancers, which are common in colorectal, gastric, endometrial, and ovarian cancers. Although MSI cancers show a high response rate to immune checkpoint inhibitors, many patients develop resistance. By acting on WRN, HRO761 may be able to stop the growth of the cancer. Chemenu has been working to develop more compounds for drug discovery. Here are the building blocks we can provide.
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