Piperidine is an azacycloalkane that is cyclohexane in which one of the carbons is replaced by a nitrogen. Although piperidine is a common organic compound, it is an immensely important class of compounds medicinally: the piperidine ring is the most common heterocyclic subunit among FDA approved drugs.
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Pyrrolidine, also known as tetrahydropyrrole, is a saturated five-membered heterocyclic ring, which is miscible with water. Pyrrolidine exists in many alkaloids and drug molecules, such as kappa opioids, antagonists of dopamine D4 receptors, and HIV reverse transcriptase inhibitors.
Cyclopropane is the smallest cyclic compound with unique structural features and physicochemical properties, which is widely used in the design of small molecule drugs. In drug design, it is often used to increase activity, fix conformation and improve PK and water solubility. The introduction of cyclopropyl groups into drugs can change various properties of molecules, such as improving metabolic stability; increasing biological activity; enhancing drug efficacy; limiting polypeptide conformation and slowing down its hydrolysis; reducing plasma clearance; improving drug dissociation and many more. Cyclopropane rings are widely found in marketed drugs, including cardiovascular drugs, central nervous system (CNS) drugs, anticancer drugs, autoimmune and anti-inflammatory drugs.
When the ends of the chains are joined together into a ring, cyclic compounds result; such substances often are referred to as carbocyclic or alicyclic compounds. Substitution of one or more of the ring carbon atoms in the molecules of a carbocyclic compound with a heteroatom gives a heterocyclic compound.
The Journal of Medicinal Chemistry recently publishes an article titled, “Discovery of Nelutroctiv (CK-136), a Selective Cardiac Troponin Activator for the Treatment of Cardiovascular Diseases Associated with Reduced Cardiac Contractility”. Heart failure (HF) is a lifelong clinical syndrome and remains a major societal concern. Cardiac myosin activators constitute a new class of inotropes and are found to be a viable therapeutic approach for increasing myocardial contractility.
CK-136 is a small molecule cardiac troponin activator that is discovered under a previous joint research program between Cytokinetics and Amgen. It acts on the sarcomere and is designed to improve myocardial contractility by sensitizing cardiac troponin to calcium, increasing actin-myosin cross bridge formation during each cardiac cycle. CK-136 is developed as a potential treatment for heart failure (HF) with reduced ejection fraction (HFrEF) and other types of heart failure, and currently under phase 1 clinical investigation.