A concise review on copper catalyzed synthesis of α-ketoamides

Published: Jan. 18, 2024

The α-keto-amides are essential building blocks for the synthesis of β-lactams and oxazolidinones. As it contains multiple reactive centers, could be a suitable starting material following reactions such as Michael addition reaction, Pictet–Spengler Mannich, Stetter reaction etc. There many US FDA approved drug molecules which bear α-keto amid moieties, boceprevir, telaprevir, fostemsavir, varespladib Copper-catalyzed α-ketoamides from acetophenones, aryl acetic acids, alkynes, acetaldehydes, α-azido ketones, 1,3-diketo compounds have been reported. This review describes research articles (since year 2012) related copper-catalyzed amides mechanism those reactions.

Language: Английский

Inhibitory Effects of Varespladib, CP471474, and Their Potential Synergistic Activity on Bothrops asper and Crotalus durissus cumanensis Venoms

Molecules, Journal Year: 2022, Volume and Issue: 27(23), P. 8588 - 8588

Published: Dec. 6, 2022

Snakebite is a neglected tropical disease that causes extensive mortality and morbidity in rural communities. Antivenim sera are the currently approved therapy for snake bites; however, they have some therapeutic limitations been extensively documented. Recently, small molecule toxin inhibitors received significant attention as potential alternatives or co-adjuvant to immunoglobulin-based snakebite therapies. Thus, this study, we evaluated inhibitory effects of phospholipase A2 inhibitor varespladib metalloproteinase CP471474 their synergistic on lethal, edema-forming, hemorrhagic, myotoxic activities Bothrops asper Crotalus durissus cumanensis venoms from Colombia. Except preincubation assay lethal activity with B. venom, mixture showed best activity. Nevertheless, mix did not display statistically differences used separately all assays. In assays, against effect induced by venom. However, independent injection compounds partially inhibited both (50%). addition, assays test inhibition edema-forming activity, exhibited followed Varespladib, but without (p > 0.05). The combination also decreased venoms. these statistical regarding < abolished hemorrhagic venom no CP471474. Finally, studies administration time-dependent manner. To propose mode action CP471474, molecular docking was performed. PLA2s SVMPs tested were targets. cases, our modeling results suggested may occupy substrate-binding cleft enzymes, which supported specific interaction amino acids active site, such His48 Glu143 metalloproteinase. residues hydrophobic channel substrate binding subsites SVMP. Our suggest mixed show varespladib, generate new treatments envenoming application field antivenom co-adjuvants.

Language: Английский

Cardiac Effects of Micrurus corallinus and Micrurus dumerilii carinicauda (Elapidae) Venoms and Neutralization by Brazilian Coralsnake Antivenom and Varespladib

Cardiovascular Toxicology, Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 22, 2023

Language: Английский