Cyclopentane Derivatives in Drug DiscoveryTo minimize torsional strain, cyclopentane puckers to adopt an envelope conformation. Cyclopentanes on drugs may serve as either the core scaffold or an appendage to occupy a hydrophobic pocket on the target such as an enzyme or a receptor. All steroid-based drugs have a fused cyclopentane ring as an integral part of the steroidal architecture. The majority of prostaglandins have a cyclopentane core structure as the consequence of oxidation of arachidonic acid by cyclooxygenases (COXs). The latest example of prostaglandin analogues is Bausch and Lomb’s latanoprostene (Vyzulta, 1) for treating open-angle glaucoma or ocular hypertension. It is a nitric oxide (NO)-donating prostaglandin F2α analogue. BioCryst’s peramivir (Rapivab, 2) is a neuraminidase inhibitor to treat influenza. Abbvie/Enanta’s glecaprevir (3, with pibrentasvir, Mavyret), with adi-substituted cycplopentane motif, is a hepatitis C virus nonstructural protein (HCV NS)-3/4A protease inhibitor. Similarly, simeprevir (Olysio, 4), Janssen/Medivir’s HCV NS3/4A protease inhibitor, has a tri-substituted cyclopentane scaffold.
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