Design, Synthesis, and Study of a Novel RXPA380-Proline Hybrid (RXPA380-P) as an Antihypertensive Agent

In drug discovery, molecular modification over the lead molecule is often crucial for the development of a drug. Herein, we report the molecular hybridization design of a novel RXPA380-proline hybrid via linking the parent compound, phosphinic peptide RXPA380, with a proline analogue. The presented synthetic route is straightforward and produces the desired product RXPA380-P in moderate yield. The C- and N-domain constructs of the angiotensin-converting enzyme of RXPA380-P appeared to be poor inhibitors of ACE as compared to the parent compound RXPA380

Advancements in tetronic acid chemistry. Part 1: Synthesis and reactions

AbstractThe preparation and the properties of the elusive tetronic acid are reviewed, including its synthesis, chemical reactivity and reactions

Chemistry of 4-hydroxy-2(1H)-quinolone. Part 2. As synthons in heterocyclic synthesis

This review presents a systematic and comprehensive survey of the utility of 4-hydroxy-2(1H)-quinolone as a building block of heterocyclic compounds. The reaction mechanism is considered as well as the scope and limitation of the most important of these approaches are demonstrated. Keywords: 4-Hydroxy-2(1H)-quinolone, Heterocycles, Microwave irradiation, Ionic liquid, Multicomponent reactions, Electrochemical route

Structure-based bioisosteric design, synthesis and biological evaluation of novel pyrimidines as antiplasmodial antifolate agents

The efficacy of most marketed antimalarial drugs has been compromised by the development of parasite resistance, underscoring an urgent need to find new drugs with new mechanisms of action. This article describes the synthesis and the in vitro antimalarial profiling of antifolate P218 analogues, by exploring a bioisosteric replacement of the carboxylic group by a phosphinic moiety as well as structural isomerization of P218. The detailed synthetic route employed to access the title compounds is described. The listed compounds exhibited low antimalarial activity against drug-resistant strains of P. falciparum including chloroquine-resistant W2

Novel glycosyl prodrug of RXP03 as MMP-11 prodrug: design, synthesis and virtual screening

Abstract Like most phosphinic acids, the potent and selective RXP03 inhibitor of different MMPs exhibited moderate absorption and low bioavailability, which impaired its use. In an unprecedented attempt, we present an interesting synthetic approach to a new class of phosphinate prodrug, glycosyl ester of RXP03, to provide a potentially improved blood–brain barrier (BBB) behavior compared to the former lead compound RXP03. To validate this speculation, a predictive study for permeability enhancer of glycosyl ester of RXP03 showed encouraging insights to improve drug delivery across biological barriers

Unprecedented Convergent Synthesis of Sugar-Functionalization of Phosphinic Acids under Metal-Free Conditions

[Image: see text] A novel TEA-catalyzed sugar-esterification of phosphinic acids was used as a general and efficient approach for the synthesis of a variety of phosphinates without any transition metal. The high efficiency of the current methodology and a convenient experimental procedure compensate for the moderate yields obtained. Another advantage is that the reaction tolerates different substituents attached to the phosphinic acids and the sugar moieties alongside the ease of isolation of the product

Novel glycosyl prodrug of RXP03 as MMP-11 prodrug: design, synthesis and virtual screening

Like most phosphinic acids, the potent and selective RXP03 inhibitor of different MMPs exhibited moderate absorption and low bioavailability, which impaired its use. In an unprecedented attempt, we present an interesting synthetic approach to a new class of phosphinate prodrug, glycosyl ester of RXP03 , to provide a potentially improved blood–brain barrier (BBB) behavior compared to the former lead compound RXP03 . To validate this speculation, a predictive study for permeability enhancer of glycosyl ester of RXP03 showed encouraging insights to improve drug delivery across biological barriers

Diastereoselective synthesis of a novel phosphinic peptide as ACE inhibitor: Fragment-based design approach

In medicinal chemistry for the purpose of lead optimization, hit selection of new isofunctional chemotypes are crucial for the success of identifying novel chemical entities of increased potency. Using fragment-based design approach with the N-selective inhibitor RXP407, a novel phosphinic peptide scaffold that consisted of modified RXP407 fragments was generated. The presented synthetic route is straightforward and produces the desired product Z-RXP407 in moderate yield. The (S,R,S,S)-Z-RXP407 analog has been evaluated for the C- and N-domain constructs of angiotensin-converting enzyme. The potency of this analog has been much lower compared to the parent compound RXP407, providing thus valuable insights regarding further design based on structure–activity relationships

Design, synthesis, cytotoxic evaluation and molecular docking of novel 1, 3, 4-thiadiazole sulfonamides with azene and coumarin moieties as carbonic anhydrase inhibitors

New thiadiazole sulfonamide derivatives were designed as human carbonic anhydrase inhibitors (hCAIs) to develop robust and novel anticancer agents. Tail modification approach was considered in designing the target compounds which were synthesized following the two-step procedure starting from 5-acetyl-3-N-(4-sulfamoylphenyl)-2-imino-1,3,4-thiadiazoline. Cytotoxic evaluation revealed the potent diazene derivative 2 with IC50 1.18 μM, 5.28 μM and 7.15 μM against MCF-7, Caco2 and HepG-2, respectively. Moreover, the dihydroxyphenyl triazene derivative 5 demonstrated IC50 3.03 μM, 5.66 μM and 12.50 μM against Caco2, HepG-2 and MCF-7, respectively. Similarly, the carbohydrazide coumarin 18 showed IC50 of 2.00 μM and 12.30 μM against Caco2 and HepG2, respectively. Molecular docking using hCAIX and hCAXII were adopted to explain the achieved cytotoxicity on molecular level with their in silico ADME evaluation

Methyl 3-(4-hydroxyphenyl)propionate

The title compound, C10H12O3, crystallizes in the orthorhombic P212121 space group. The structure contains a phenolic group with the OH being coplanar with the phenyl ring. The structure exhibits significant hydrogen bonding between the O—H group of one molecule and the CO group of an adjacent one. These O—H...O=C interactions form chains of molecules parallel to the b axis. No π–π or C—H...π intermolecular interactions are observed