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.
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.
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