This Drug Synthesis is Literally Breathtaking | Medicinal Chemistry & Organic Synthesis

This molecule might look like any other 'flat drug' - but there's a mystery hidden behind its synthesis! Coupled with the fact that it showed promise in asthma due to its novel mechanism, you could say that it's breath-taking (actually more like breath-giving, but I figured no one will understand this). Watch this video to learn more about organic synthesis, drug development and more! https://total-synthesis.com/organic-c... 🧑‍🎓➡️ Free organic chemistry practice problems   / totalsynthesis_official   👉 Follow me on Instagram for updates on random research, mechanism quizzes and interesting news! https://www.total-synthesis.com 00:00 A breath-taking synthesis 00:23 Structure of our target molecule 01:37 Intro to PI3K enzymes and inhibitor drugs 03:41 Levels of chemistry sophistication 05:09 Retrosynthesis of AZD8154 and overview 05:57 Forward synthesis # 1 07:26 What was the problem? 08:19 Forward synthesis # 2 11:10 How legit is the solution? 12:03 FDA stance on PI3K inhibitors, and conclusion Disclaimer - This channel does not provide medical advice! No information on this channel is intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of information on Youtube. Key references: Discovery of AZD8154, a Dual PI3Kγδ Inhibitor for the Treatment of Asthma | J. Med. Chem. 2021, 64, 8053 Class I Phosphoinositide 3-Kinase PIK3CA/p110α and PIK3CB/p110β Isoforms in Endometrial Cancer | Int. J. Mol. Sci. 2018, 19, 3931 The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review | Cancers 2021, 13, 3949 Discovery of Highly Isoform Selective Orally Bioavailable Phosphoinositide 3-Kinase (PI3K)-γ Inhibitors | J. Med. Chem. 2018, 61, 5435 An Intramolecular Diels–Alder Approach to the Isoindolinone Core of AZD8154 | doi.org/10.1021/acs.oprd.3c00507 Selection and Development of the Manufacturing Route for EP1 Antagonist GSK269984B | Org. Process Res. Dev. 2010, 14, 820 Characterisation of pharmacokinetics, safety and tolerability in a first-in-human study for AZD8154, a novel inhaled selective PI3Kγδ dual inhibitor targeting airway inflammatory disease | Br J Clin Pharmacol. 2022, 88, 260 Copanlisib for treatment of B-cell malignancies: the development of a PI3K inhibitor with considerable differences to idelalisib | Drug Des Devel Ther 2018, 12, 2577 Recommended organic chemistry books: Winter; Organic Chemistry I For Dummies (start here if you are absolutely friggin clueless) | https://amzn.to/4fmF97q Clayden, Greeves, Warren; Organic Chemistry (basic organic chemistry knowledge) | https://amzn.to/4ul57ft Wyatt, Warren; Organic Synthesis: The Disconnection Approach (excellent introduction to retrosynthesis) | https://amzn.to/4fmF97q | https://amzn.to/3Q529xn Kurti, Czako; Strategic Applications of Named Reactions in Organic Synthesis (extensive toolkit of functional group reactions and applications thereof with common conditions) | https://amzn.to/43cbzKH Grossmann; The Art of Writing Reasonable Organic Reaction Mechanisms (building intuition for intermediate and advanced reaction mechanisms) | https://amzn.to/4dOiIXA Nicolaou; Classics in Total Synthesis 1-4 (simply legendary series) | https://amzn.to/4o986pz | https://amzn.to/3ROsRLp | https://amzn.to/3S4vCYV | https://amzn.to/4dPI9YL Nicolaou; Molecules That Changed the World (the world's most important molecules and their impact on everyday life) | https://amzn.to/4odZwWW Carreira, Kvaerno; Classics in Stereoselective Synthesis (compilation of the groundbreaking methods of stereoselective synthesis and application to synthesis of stereochemically complex structures) | https://amzn.to/4dZk9kH Anslyn; Modern Physical Organic Chemistry (almost anything you will need for (organic) physical chemistry) | https://amzn.to/4gwOZUL