Dinka Mulugeta’s Post

One of the key applications of AI in medicinal chemistry is the prediction of the efficacy and toxicity of potential drug compounds. Classical protocols of drug discovery often rely on labor-intensive and time-consuming experimentation to assess the potential effects of a compound on the human body.

Most Trusted. Most Cited. Most Read. Publish your next drug discovery/medicinal chemistry campaign with the Journal of Medicinal Chemistry (https://lnkd.in/dFrsv9E).

My recent Perspective in the Journal of Medicinal Chemistry! It is a summary of the current medicinal chemistry tools used in Gram-negative antibacterial discovery, the fundamental gaps when applying eukaryotic "rules" to bacteria, and an optimistic view of future medicinal chemistry efforts. Big thanks to Adam Duerfeldt for support and direction in writing this piece.

Creative Design in Chemistry   In medicinal chemistry, the difference of one atom in a compound can have an impact on the bonding and stability which can affect drug effectiveness. One of the most common modifications done to drugs is the changing of an aromatic carbon to a nitrogen atom. The prevalence of having this nitrogen has resulted in the idea of having a “necessary nitrogen atom” for effective drug design. The problem with this method is that the changing of a single atom in practice is indirect and a restart of synthesis needs to happen to produce the desired change.   However, a paper1 published at the end of 2023, suggests a direct transformation done via oxidative restructuring with ozone gas. This reaction forms a ring-opened intermediate which is electrophilic and allows for the reaction that will result in the release of a carbon atom and reforming of the ring. This method allows for more accurate modification due to the less effect it has on the compound's skeleton-rotation which is an often-seen pitfall in the synthesis of a modified drug. This process of analysis and modification is something that I have had to do during my time at the University of Newcastle. During the completion of a Medicinal and Biological chemistry, from given structures and biological test results I was asked about how to improve drug effectiveness. Using my knowledge and critical thinking, I suggested ways in which modifications could be used to improve the drugs activity as well as provide a synthesis for the suggestions. I received a 80% grade for my answers towards these questions. #SCIE2001 #BScUoN (1)    Woo, J.; Stein, C.; Christian, A. H.; Levin, M. D. Carbon-To-Nitrogen Single-Atom Transmutation of Azaarenes. Nature 2023, 623 (7985), 77–82. https://lnkd.in/e5WijiH2 Pixabay, https://lnkd.in/e3jXdkWE , (Creative Commons licenced).

INSPIROCHEM LLP offers comprehensive R&D services, tailoring custom synthesis solutions for both industrial and academic research projects. Over the past two years, we have successfully delivered leads, drug-candidates, and intermediates to our valued partners, contributing to the success of their projects. Our expertise in custom synthesis includes: • Synthesis of novel and well-known small molecules, APIs, and impurities with purity levels ranging from 90% to 99%. • Synthesis of compound libraries for in vitro tests (10-50 compounds per scaffold). • Chemical reactions with a reagent volume of up to 50 liters, utilizing both lab and pilot-industrial systems. Purification of large reaction volumes is achieved using methods such as distillation, chromatography, recrystallization, etc. Choosing INSPIROCHEM LLP: Here's Why - Proven track record of delivering leads and drug-like candidates. - Top research scientists and mentors with a background in medicinal chemistry. - Well-earned reputation in designing and library synthesis for in-vitro testing. - Adaptability to meet specific customer medicinal chemistry requirements. - Transparent communication, regular reporting, and meetings. - Upon project completion, we provide chemistry schemes, experimental data, ELNs, and analytics for publication. #Customsynthesis #ResearchProjects #MedicinalChemistry #API #Intermediates #drugdesign #LibrarySynthesis

#Multistep and #multivectorial assembly line library synthesis in flow. #FlowChemistry Organic synthesis has traditionally been like an art form, where scientists create complex molecules through a mix of chosen reactions, often relying on trial and error. #Organic synthesis is a crucial part of the multidisciplinary process of #drugdiscovery. In recent years, there has been a growing interest in rapidly generating analog libraries in #pharmaceutical companies. To accelerate #medicinal chemistry programs, automated synthesis protocols have emerged as a promising approach.#Flow chemistry for modular multistep synthesis for library creation offers the potential for the rapid generation of analogs in a combinatorial manner, unlocking new possibilities in drug discovery.

PFIZER MED DESIGN PUBLICATION: How are you feeling when your project decides that you need >10 grams of this molecule for a key study? The synthetic chemists on Pfizer's C5aR antagonist program and the Chemical R&D team certainly stepped up, displaying their skill and versatility, in what is less familiar chemical space for many of us. Eleven steps on-resin followed by four off for an overall yield of 6% eventually became 35% on scale up. This is a polar and complex molecule to deal with in all dimensions! Many Pfizer Medicine Design past and present on this paper including Yiqing Feng, Carmen Garcia-Irizarry and the recently retired Kathleen F.. However, I'd like to single out corresponding author Ricardo Lira, now of our ERS team, but Synthesis Lead for the program at the time. I'll also squeeze in a mention of my Ley group PhD fume hood pal and dear friend of nearly 30 years Peter Jones too, who was the program's Chemistry Design Lead. Link to paper in Comments: #pfecolleague

Chemical Solutions for Health: Progress in Medicinal Chemistry Research Url: https://lnkd.in/gB8ugXQu #ChemistryInnovation #ChemicalAdvancements #NewChemicalFrontiers #ChemicalBreakthroughs #InnovativeChemistry #ChemicalResearch #ChemicalDiscoveries

#CMI0324: Chemistry & Life Sciences Flow #Chemistry in Drug Discovery: Exploring the Benefits and Considerations for Synthesis For the synthesis of compounds in #pharmaceutical applications, it is important to select the most appropriate flow chemistry regime and equipment based on the goals of the application. #Flowchemistry enables safe, precise and efficient synthesis of compounds that can be scaled from pilot projects to manufacturing. Automated flow systems can quickly synthesize a wide range of compounds, making it ideal for generating libraries for early stages of drug discovery. This article delves into the key considerations when using continuous or segmented flow chemistry approaches. Flow chemistry is when reactants are continuously pumped into a flow reactor with efficient mixing, and the product is collected. However, the development of automated flow systems is now allowing segmented flow regimes, using careful coordination of smaller aliquots of reactants to create smaller quantities of products. It is therefore important to carefully consider the appropriate flow regime to match your aims and experimental needs. Flow Chemistry: Continuous Flow Continuous flow describes chemical reactions occurring in flow reactor systems with cylindrical geometries, where reactants are continually introduced and mixed radially, effectively functioning as a series of ‘plugs’—or slugs—flowing through the system. Figure 1 highlights this phenomenon, where each coherent plug has a given length (dx) and volume (dV), traveling in the longitudinal direction of the reactor. The ‘ideal’ plug flow model assumes a steady state, no mixing between plugs, a constant density, and that only one reaction occurs. (...) Read more about this topic from Leandro Carvalho, Senior Product Specialist, and Omar Jina, Chief Commercial Officer, Syrris, Royston, UK, in our latest #CMI issue: https://lnkd.in/efsUQj9e  

"Grateful to share a momentous group photo from the Department of Chemistry at Women's Christian College, celebrating 70 years of excellence! 📸 On December 15th, 2023, we commemorated this milestone with a National Seminar on 'New Frontiers in Organic Chemistry, Pharmaceutical Chemistry, and Nanoscience Research.' It was a day filled with insightful discussions, groundbreaking research, and the spirit of collaboration. Grateful to be part of this vibrant community dedicated to advancing the field of chemistry. #WCC #Chemistry #70YearsOfExcellence #NationalSeminar #OrganicChemistry #PharmaceuticalChemistry #Nanoscience #Research #Celebration"