Ahmed Abdel-Hay, PhD’s Post

Synergistic effect of polymers in stabilizing amorphous pretomanid through high drug loaded amorphous solid dispersion

📚 Chromatographic Determination of Permeability-Relevant Lipophilicity Facilitates Rapid Analysis of Macrocyclic Peptide Scaffolds #bro5 #permeability

PHOSPHORILATION CAN IMPROVE STABILITY AND REDUCE TOXICITY OF ANTIMICROBIAL PEPTIDES (AMPs). A series of peptides and their corresponding phosphorylated forms were synthesized. The results showed that ALL phosphorylated peptides displayed reduced toxicity and enhanced stability compared to their unphosphorylated counterparts. #peptide #AntimicrobialPeptides #AMP #phosphorilation Z. Ba et al. Journal of Medicinal Chemistry 2024. https://lnkd.in/dRVSi7n9

Adding an alkyl or an alkenyl group to a molecule can change its properties drastically. Be they small or bulky, short- or long-chain, the changes brought about by the introduction of these hydrocarbon groups are what makes them interesting all the way from pharmaceutical chemistry to materials science. However, the reagents for these transformations are often difficult to handle, not least due to their often significant health hazards. In their Review, Johanna Templ and Michael Schnürch (Technische Universität Wien) provide a comprehensive overview of an alternative substance class that can be used for this purpose: quaternary #ammonium salts, QAS. These non-toxic and easy-to-handle #reagents can be used in various #alkylation strategies, broadly classified into metal-free nucleophilic substitutions and transition metal-catalyzed transformations. Despite their benefits and many successful examples, the full potential of QAS is not yet explored. Making a convincing case for change, the authors provide concrete guidance for researchers. Our Pick of the Week, published #OpenAccess in Chemistry – A European Journal #ChemEurJ: “Strategies for using Quaternary Ammonium Salts as Alternative Reagents in Alkylations” https://ow.ly/gVSV50Rzz7G

https://lnkd.in/gDPQx9Gw The IDH1 mutant inhibitor, a tricyclic diazepine functionalized with a zigzag morphorine and chiral cyclohexyl acid, was required in kilogram-scale quantities for clinical trials. The diazepine core was synthesized via Pd-catalyzed C-N coupling, followed by Boc protection and reductive cyclization. The use of Pt-V/C for reduction was the key to keep the chloro group intact while reducing the nitro group and subsequently formed imine in one-pot. The core was then acylated with an acyl chloride derived from the chiral cyclohexyl acid in MeCN, and isolated through water quenching at low temperature with seeding. Subsequently, the zigzag morphorine was coupled with the acylated core under Pd-catalytic conditions, and Boc deprotection was performed with MsOH to yield the final product. Additionally, they demonstrated dynamic mono-acylation of unprotected diazepines, where the acyl group on the undesired N11 group was selectively transferred to the desired N6 position at elevated temperatures without the need for an external base.

GELDANAMYCIN, AFTER HALF A CENTURY SINCE IT WAS ISOLATED FOR THE FIRST TIME Geldanamycin remains a driver in the medicinal chemistry of heat shock protein 90 (Hsp90) inhibition, even half a century after its original isolation from nature. This Perspective "open access" in J. Med. Chem. focuses on the properties of the benzoquinone ring of the natural product that enable a range of functionalization reactions to take place. A natural Hsp90 inhibitor Lead Compound for Medicinal Chemistry. #geldanamycin #medchem #hsp90

An informative webinar that will present strategies to reduce solvents and reagents during solid-phase peptide synthesis. Discover how to completely eliminate the use of dimethylformamide (DMF) from your processes!

https://lnkd.in/dheNiyW Sulfinamide Synthesis Using Organometallic Reagents, DABSO, and Amines

In a recent poster presentation from #WADC, we utilized the characteristics of the membrane absorbers, Sartobind® S and Phenyl, for aggregate and #payload clearance while polishing an #ADC in a single chromatographic run. The application of the tandem membrane chromatography system presented a novel and efficient purification scheme that was realized during ADC manufacturing. Access the poster here: https://lnkd.in/g5YWiTyw #CDMO #CRO #bioconjugation #drugdevelopment

#MTCiting in #OrgLett. Using dirhodium(II) catalyst loadings, cyclopropanation of N-Boc-2,5-dihydropyrrole with ethyl diazoacetate is effectively performed. Exo- or endo-3-azabicyclo[3.1.0]hexanes are formed without chromatographic purification. https://okt.to/hTKd3n