Pyridine is a six-membered heterocyclic compound containing one nitrogen heteroatom. Pyridine and piperidine are the most frequently occurring heterocyclic building blocks in drug molecules. According to incomplete statistics, there are currently more than 180 drugs containing pyridine or piperidine structure that have been marketed, nearly 1/5 of the drugs approved for marketing in recent years contain these two structures.
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Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one methine group (=CH−) replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid with a distinctive, unpleasant fish-like smell.
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.
Over 30% of all human cancers, including a certain percentage of pancreatic, colorectal, lung cancers, and AML are driven by mutations of RAS genes. There is a significant unmet medical need in RAS mutant cancers.
Revolution Medicines’ investigational drug, RMC-6236 is an oral, non-covalent, RAS (ON) inhibitor that is selective for the active, GTP-bound state of both mutant and wild-type variants of the canonical RAS isoforms. RMC-6236 is under clinical phase I studies as monotherapy in NSCLC and PDAC, and advanced solid tumors harboring KRAS G12X mutations.
Revolution Medicines announced preliminary positive data for its RAS(ON) G12D-selective covalent inhibitor RMC-9805 in previously treated pancreatic ductal adenocarcinoma (PDAC) patients. The analysis showed that the disease control rate of PDAC patients treated with RMC-9805 was as high as 80%. RMC-9805 is a potential ‘first-in-class’ oral RAS(ON) G12D-selective inhibitor, that is being evaluated in trials to examine its efficacy and safety in patients with solid tumors carrying KRAS G12D mutations when used as a single agent or in combination with the pan-RAS inhibitor RMC-6236. Chemenu has been working to develop more compounds for drug discovery. Here are the building blocks we can provide.