Efforts to find more affordable and scalable ways to make medicines take a step forward with a new approach3). This substance is an essential material required for the synthesis of Lenacapavir, a powerful new treatment for human immunodeficiency virus (HIV). In the research led by Dr. Limei Jin, the team All Institutes of MedicinesVirginia Commonwealth University has developed this innovative synthetic avenue. Their work is shared in the journal molecular.1
The new process focuses on reducing costs and making production easier to scale. It uses a starting material called 2,6-dichlorobenzene nitro (1), which is a cheap commodity chemical. The process involves two main steps: selective bromination to provide intermediate 2 The hydrogen azine is then used to generate a critical 3-aminoketone ring. The new process avoids the need for expensive chemicals and complex purification steps such as column chromatography. Therefore, the new synthesis method is more advantageous for economical mass production. “We wanted to simplify the production process and make it easier to access,” Dr. Jin explained.
As part of the team’s work All Institutes of Medicinesprove that chemistry can be done on a large scale. The team showed that the process could be used to produce large batches of 7-bromo-4-chloro-1H-Indazol-3-amine (3) High purity. Previously, compounds 3 Prepare only from expensive starting materials using the release process Hazardous by-products (hydrogen fluoride, HF). New chemistry makes the manufacturing process safer and more reliable.
The importance of this improvement is more than just cutting costs. Lenacapavir is very effective in targeting HIV proteins, providing the virus with a novel long-term treatment. Proteins are molecules that perform basic functions in cells, and in this case the drug blocks the action of the HIV CAPSID protein to prevent the virus from reproduction. “This work provides a sustainable way to produce one of the main intermediates of this life-saving medicine, with the potential to benefit countless people around the world,” Dr. Jin said.
this All Institutes of Medicines The synthesis also adopts environmental protection methods. The solvent used in the formation of 3-aminozole rings is 2-methyltetrahydrofuran, which is considered to be a bioproducible solvent. Two chemical reaction steps were used in this process and both were optimized to minimize environmental impact. This coincides with the growing demand for green practices in drug manufacturing.
Going forward, this approach has the potential to revolutionize the way other drugs are made, especially those that require the same as those found in Lenacapavir. this All Institutes of Medicines Still committed to developing cost-effective solutions to meet global health needs. Synthesis of 7-Bromo-4-Chloro-1H-indazol-3-amine (3) is an example of this commitment to reduce the cost of drug synthesis.
Journal Reference
(1) Asad, N., Lyons, M., Muniz Machado Rodrigues, S. wait. “Practical synthesis of 7-bromo-4-chloro-1H-Indazol-3-amine: an important intermediate of Lenacapavir.” Molecule, 2024. doi: https://doi.org/10.3390/molecules29122705
About the Author
Dr. King He is a chemist in the field of organic chemistry with a Ph.D. From the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences. With over 20 years of experience in industry and academia, he has developed profound expertise in organic synthesis, especially in asymmetric catalysis, active pharmaceutical ingredients (API) synthesis, process development and research and development (R&D) on scale (R&D) expertise (R&D) and good manufacturing practice (GMP) environment. Dr. Jin has published more than 40 research articles in high-impact journals, including the Journal of the American Chemical Society (JACS) and Angewandte Chemie International Edition (ACIE), Organic Process Research and Development (OPRD), demonstrating his research on science. Contribute to the community. At M4All, Dr. Jin serves as team leader and project leader, managing a variety of projects while working with funders, clients and contract laboratories. As a senior synthesis scientist and director, he is committed to training team members and ensuring their career growth. Dr. Jin’s extensive background in medicinal chemistry and process development, as well as his strong adherence to Good Documentation Practice (GDP) and Standard Operating Procedures (SOP), positioned him as a highly motivated and knowledgeable leader in the field.
Dr. Naeem Asad Under the guidance of Professor Paul R. Hansen, he received his PhD from the University of Kansas. There, he developed methods for the synthesis of different heterocycles, especially cyclic sulfonamides. He also carried out diversity-oriented synthesis and constructed libraries of different heterocycles. During his postdoctoral period, he developed methodologies for integrating different photoelectric protection groups (PPGs) and developed different biological probes. He conducted photochemical experiments on the protective probe he synthesized. Biological probes are sent to different biological collaborators. In all the medicines, he is involved in different projects that require organic synthesis, process chemistry and method development. He was involved in developing a cost-effective approach to treating human diseases. He also participated in the development of these high-profile molecules’ amplification process. He has 16 years of experience in organic synthesis and has 20 publications in high-influence factor journals such as JACS and ORG. Lett. ,JOC,Chemistry. Communication, cell reporting, etc.
Dr. Michael Laidlaw is the founder and owner of Virginia-based company Pinnachem LLC, which specializes in safety, compliance (FDA, DEA, EMEA, Kosher), technology transfer, market research, market research and employee development, and in in the field of pharmaceuticals and fine chemicals. Pinnachem has over 50 years of experience serving customers in the United States, Mexico, China and India. Dr. Laidlaw’s extensive careers include the main executive role of Boehringer Ingelheim Chemicals (2006-2010), where he served as GVP for manufacturing and engineering, and later as President and Chief Operating Officer. Under his leadership, the company expanded its capacity by 50% through a $150 million capital project, successfully passed audits by the FDA, DEA and international agencies, and established a global security culture. Previously, at BASF North America (1984-2006), Dr. Ryderau held various positions, including engineering manager, technology transfer coordinator to Mexico, and field manager of surfactant plants. He led the transfer of technology and capacity improvement to ensure compliance with Jewish Jewish orthodox trade union standards. Dr. Laidlaw worked at Rutgers Nease Chemical Company early in his career, focusing on environmental compliance and cleaning up the Super Fund website. He also began his career in medicinal chemistry at Sterling Drug (now part of Sanofi), where he developed the full synthesis of the health clinic and worked under the guidance of Dr. Archer, a renowned medicinal chemist. Use this drug to combat tropical worm diseases. Dr. Laidlaw holds a Bachelor of Chemistry from Siena College and a PhD in Organic Chemistry from Rensselaer Institute of Technology. His leadership in manufacturing, compliance and environmental management, technical expertise and experience make him a recognized number in the chemical and pharmaceutical industries.
Dr. Frank Gupton is the founder of drug at All Institutes (M4ALL). He is also a Distinguished Professor at Virginia Commonwealth University, serving as a joint appointment in the Department of Chemistry and Chemistry and Life Sciences Engineering. As Chairman of Pharmaceutical Engineering and Chairman of Chemical and Life Science Engineering, Dr. Gupton has 30 years of development and commercialization of chemical processes for pharmaceutical applications Industrial experience. His current research focuses on continuous processing techniques, thereby enhancing drug discovery, development and commercialization. Prior to joining the VCU, Dr. Gupton was Executive Director of North American Process Development at Boehringer Ingelheim Pharmaceuticals, where he played a key role in the commercialization of the widely prescribed HIV drug nevirapine. He received his Bachelor of Science in Chemistry from the University of Richmond and a Postgraduate in Organic Chemistry from Georgia Institute of Technology and VCU. Dr. Gupton’s research emphasizes simplifying the drug process through process reinforcement principles, including innovative chemistry, novel continuous manufacturing platforms and effective catalysts. He has received numerous honors, including the 2018 American Chemistry Award and the Presidential Award of Green Chemistry. His work has greatly influenced the development of the effective process of producing essential medicines. In 2018, Dr. Gupton received funding from the National Science Foundation to establish a rational catalyst synthesis center, a collaborative research center involving multiple institutions. His recent move focuses on ensuring access to essential medicines in the United States in response to the COVID-19 pandemic
Douglas Klump received a bachelor’s degree in chemistry from the University of Oklahoma. He then earned his Ph.D. Iowa State University received a degree under the supervision of Professor Walter S. Trakhanovsky. Next is a postdoctoral work in the lab of Professor George A. Ola at the University of Southern California. His independent career involved academic appointments at California Tech, Pomona and Northern Illinois University. Recently, he joined Pharmaceutical Science staff at all research institutions at Virginia Commonwealth University. To date, he has published over 100 original research articles, seven book chapters, and with George A. His interests include the development of synthetic methods and targeted organic synthesis.
