Drug Discovery with Privileged Building Blocks
Tactics in Medicinal Chemistry
Drug Discovery with Privileged Building Blocks traces back PharmaBlock’s founding philosophy of designing privileged building blocks. High-quality building blocks are crucial not only to biological activities of different molecules but also to ADMET properties, which eventually will impact the success rate of drug discovery projects. A thorough study of how building blocks perform in drug molecules and a regular analysis of new building block structures in the latest researches have proven to be a fruitful strategy to generate novel building blocks. Using this strategy, PharmaBlock has supplied the drug industry with a great number of building blocks, which are increasingly being adopted by drug hunters, and these are identified in this book.
Each chapter may be read and studied without learning the previous chapters. This book will be a good starting point for novice medicinal chemists, and veteran medicinal chemists will find it useful as well.
- The book covers privileged building blocks appearing most frequently on patents for novel drugs.
- The latest relevant tactics are explained in the context of drug design and medicinal chemistry.
- Key synthesis, especially large-scale synthesis, is described.
- The most recent literature references are cited.
Table of Contents
Preface 1. Alkynes; 2. Azaindoles; 3. Azetidines; 4. Bicyclic Pyridines Containing Ring-junction N; 5. Bicyclo (1.1.1)pentyl (BCP) as an sp3 Carbon-rich Bioisostere for para-Phenyl and tert-Butyl Groups; 6. Bicyclo[2.2.2]octane (BCO) as A 3D-rich Bioisotere for the para-Phenyl Group; 7. Bicyclo[3.1.0]hexanes; 8. Bridge-Fused Rings as m-Phenyl Bioisosteres; 9. Cubanes, Are We There Yet?; 10. Cyclobutanes; 11. Cyclohexanes; 12. Cyclopentanes; 13. Cyclopropanes as Metabolically More Robust Bioisoteres for Linear Alkyl Substituents; 14. Deazapurines; 15. Furopyridines; 16. Indazoles; 17. Indoles; 18. Oxetanes; 19. Piperidine, the Enchanted Ring; 20. Pyrazines; 21. Pyrazoles; 22. Pyridazines; 23. Pyridines - The Magic of Phenyl-Pyridyl Switch; 24. Pyrimidines; 25. Pyrrolidines; 26. Pyrrolotriazines; 27. Spiroazetidines; 28. Spirocyclic Piperidines; 29. Spirocyclic pyrrolidines; 30. Spirooxetanes; 31. Tetrahydropyrans; 32. Trifluoromethylpyridines. Index
Dr. Jie Jack Li is an established chemist with over 20 years of experience in both medicinal chemistry and process chemistry. He is also widely published as an author or co-author of 34 peer-reviewed articles, 12 patents, and 29 books. Prior to joining ChemPartner, Dr. Li worked at Pfizer, BMS, and Revolution Medicines in oncology, antivirals, metabolic disease, CNS, anti-inflammatory, and dermatology, targeting enzymes, receptors, or ion channels. Dr. Li was also a professor at the University of San Francisco for four years, teaching organic and medicinal chemistry. He earned his Ph.D. from Indiana University and was a post-doctoral fellow at MIT.
Dr. Minmin Yang received his PhD in organic synthesis from Auburn University, US in 2001, and did post-doctoral training at the same school from 2002 to 2004. Prior to founding PharmaBlock, he worked with increasing responsibilities from group leader to section head of medicinal chemistry at Roche Palo Alto and Roche China for 4 years. Dr. Yang has authored 80 publications, including 16 international patents.