Gagan Kukreja’s Post

ONE (aziridine) RING TO RULE THEM ALL! The first total synthesis of potent antimicrobial agent Dynobactin A. A convergent approach proceeding in only 14 steps (LLS) from commercial materials should facilitate the synthesis of numerous analogs for medicinal chemistry studies. An awesome use of aziridines. A much under utilized ring system. https://lnkd.in/gd37UAFy

Pd(0)-catalyzed Heck/C(sp3)–H activation cascade for the synthesis of spirocyclopropyl oxindoles from easily accessible ortho-bromoacrylamides. From a Medicinal Chemist perspective this spirocyclopropanation strategy has a lot to offer! https://lnkd.in/gMdN9Rzr

Attention fellow chemists and researchers! Let’s talk about the secret sauce behind oral bioavailability for PROTACs. Molecular properties like solvent-exposed H-bond donors (eHBD), acceptors (eHBA), polarity, lipophilicity, and molecular weight are the VIPs in this game. And here’s the kicker: keeping eHBD ≤ 2 in apolar environments is like ensuring your molecular guests don’t overstay their welcome. It’s crucial for higher bioavailability. So, next time you’re in the lab, remember: it’s all about the right balance. Too many H-bond donors? Your compound might just be too clingy. #MedicinalChemistry #Bioavailability #PROTACs #ChemistryRocks #DrugDesign

Late-stage functionalization (LSF) has garnered significant interest from medicinal chemists due to its challenging nature and efficiency in derivatizing advanced intermediates. In this article, the authors demonstrate the Ru-catalyzed C-H arylation of medicinally relevant N-aryl triazoles and tetrazoles, which enables LSF. #arylation #ruthenium #triazoles #tetrazoles #LSF #drugdesign https://bit.ly/3yphWhh

With the ability to extend groups into specific conformational space crucial in developing potent molecules, there is yet another reason for Medicinal Chemists to explore cyclopropane ring in their designs to alter the conformation of some of the most common scaffolds used in medicinal chemistry The knowledge comes from the surprising conformational effect that in comparison to simple di-alkyl substitution, small rings, in particular cyclopropane commonly used as isostere for multiple groups, including alkenes can cause substituents on cyclohexanes, six-membered ring heterocycles and in acyclic systems to favour axial conformation that can help medicinal chemists increase three-dimensionality of drug candidates. What's quite different and unique is the fact that the cyclopropyl effect influences the position of substituents on six-membered rings to favour the axial orientation, which is usually more unstable, and the effect grows more significant as alkyl groups get larger Driving tert-butyl axial: the surprising cyclopropyl effect https://lnkd.in/gySnwuZ8 https://lnkd.in/gs88vtqr

📣🎙️Reminder: Mastering hERG: Medicinal Chemistry Strategies for Mitigating Cardiotoxicity Risks | https://lnkd.in/dGd_JsDb Thu, Aug 15th, 2024 9 AM PDT / 12 PM EDT / 6 PM CEST Join us for a Coffee Chat with our team—Dennis X. Hu, Matthew Hesse and Dennis Koester—as they discuss strategies and tactics medicinal chemists use to minimize hERG-related risks during lead optimization. This session will provide valuable insights and practical approaches to addressing hERG liabilities. You can submit your questions during the registration process and engage with our team in a live Q&A session. Don't miss this opportunity to learn from industry case studies that successfully mitigated hERG liabilities. Register here: https://lnkd.in/dGd_JsDb

Selecting and optimizing the right linker for your bioconjugate drug candidate is easy in theory but difficult in practice. Enter the “Linker Selection Tool”. It allows you to select your parameters, narrow down the options, and land on your ideal linker design. Try it out: https://bit.ly/3U7ebEq #BioDesign #ADC #Bioconjugation #Therapeutics

Streamline your biosimilar development with Octet®️ BLI systems, offering real-time, label-free binding assessment. With the ability to analyze unpurified samples directly, Octet®- Affinity, Binding Kinetics and Concentration®️ reduce preparation costs and time to results, enhancing product quality and regulatory compliance. Discover how Octet®️ BLI systems can be used at multiple stages during biosimilar development, from initial characterization, glycol analysis, and preliminary comparability studies to the final binding studies required for regulatory submissions. Download the brochure now: https://ow.ly/oz7s50SsJYK #Sartorius #OctetBLI #BiosimiliarDevelopment #QualityControl #Diagnostics #Laboratory #LabEssentials

Check out our latest article in Drug Discovery Today, titled "Exploring the Chemical Space of Orally Bioavailable PROTACs" together with Giulia Apprato, Diego García Jiménez, Yoseph Atilaw, Mate Erdelyi, Giuseppe Ermondi, Giulia Caron and Jan Kihlberg Take home: • Most of the reported orally bioavailable proteolysis targeting chimeras (PROTACs) are based on #cereblon. • The oral druggable space of PROTACs is identified better by 3D descriptors than by 2D descriptors. • #PROTAC lipophilicity/polarity and #chameleonicity can be optimized by chromatography. • In silico methods show promise for the prediction of 3D descriptors of PROTACs. 📰 Read the full article here: https://lnkd.in/dCwKKKkW 💻🔬 #DrugDiscovery #PROTACs #chemicalspace #cellpermeability #NMR #chromatography

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